Compounds > efatutazone
Page last updated: 2024-11-11

efatutazone

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

efatutazone: a high-affinity PPARgamma agonist with antineoplastic activity [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9832447
CHEMBL ID3545280
SCHEMBL ID3246054
MeSH IDM0580926

Synonyms (31)

Synonym
HY-14792
inolitazone
unii-m17ill71mc
223132-37-4
efatutazone
efatutazone [inn]
m17ill71mc ,
CS-0778
5-[4-[6-(4-amino-3 ,5-dimethylphenoxy)-1-methyl-1h-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione
5-(4-{[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1-h-benzimidazol-2-yl]methoxy}benzyl)-1,3-thiazolidine-2,4-dione
JCYNMRJCUYVDBC-UHFFFAOYSA-N
5-[4-[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1h-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione
efatutazone [who-dd]
2,4-thiazolidinedione, 5-((4-((6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1h-benzimidazol-2-yl)methoxy)phenyl)methyl)-
rac-5-((4-((6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1h-benzimidazol-2-yl)methoxy)phenyl)methyl)-1,3-thiazolidine-2,4-dione
SCHEMBL3246054
AC-31435
CHEMBL3545280
AKOS030526729
DB11894
bdbm50450236
FT-0737589
BCP07478
5-(4-((6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1h-benzo[d]imidazol-2-yl)methoxy)benzyl)thiazolidine-2,4-dione
efatutazone;cs-7017;rs5444
DTXSID60944956
5-[(4-{[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1h-benzimidazol-2-yl]methoxy}phenyl)methyl]-4-hydroxy-1,3-thiazol-2(5h)-onato(2-)
Q21083321
nsc-764579
nsc764579
5-[[4-[[6-(4-amino-3,5-dimethylphenoxy)-1-methylbenzimidazol-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione

Research Excerpts

Overview

Efatutazone is a highly selective agonist of peroxisome proliferator-activated receptor gamma. It has antiproliferative effects in a range of malignancies.

ExcerptReferenceRelevance
"Efatutazone is a novel later generation PPAR-γ agonist that selectively activates PPAR-γ target genes and has antiproliferative effects in a range of malignancies."( Small molecule agonists of PPAR-γ exert therapeutic effects in esophageal cancer.
Baba, H; Baba, Y; Hirashima, K; Ishimoto, T; Iwatsuki, M; Kurashige, J; Morita, M; Oki, E; Sawayama, H; Shiose, Y; Sugihara, H; Watanabe, M; Yoshida, N, 2014)		1.12
"Efatutazone is a highly selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a therapeutic target for carcinogenesis."( Phase I study of Efatutazone, an oral PPARγ agonist, in patients with metastatic solid tumors.
Boku, N; Jikoh, T; Murakami, H; Ono, A; Onozawa, Y; Takahashi, T; Tsushima, T; Yamamoto, N; Yamazaki, K, 2014)		2.18

Treatment

Efatutazone treatment reduced rates of mammary epithelial cell proliferation and development of hyperplastic alveolar nodules. It increased expression levels of the PPARγ target genes AdFP, Fabp4, and Pdhk4 in preneoplastic mammary tissue.

ExcerptReferenceRelevance
"The efatutazone-treated lesions were less invasive with fewer CD44+/p63+ basal progenitor cells."( The PPARγ agonist efatutazone delays invasive progression and induces differentiation of ductal carcinoma in situ.
Boeckelman, J; Furth, PA; Kallakury, BV; Kietzman, WB; Ory, V; Riegel, AT; Wellstein, A, 2018)		1.3
"Efatutazone treatment reduced rates of mammary epithelial cell proliferation and development of hyperplastic alveolar nodules and increased expression levels of the PPARγ target genes Adfp, Fabp4, and Pdhk4 in preneoplastic mammary tissue."( The PPARγ agonist efatutazone increases the spectrum of well-differentiated mammary cancer subtypes initiated by loss of full-length BRCA1 in association with TP53 haploinsufficiency.
Furth, PA; Kallakury, BV; Nakles, RE, 2013)		1.45

Compound-Compound Interactions

Efatutazone combined with FOLFIRI demonstrates an acceptable safety profile and evidence of disease stabilization in Japanese patients with mCRC.

ExcerptReferenceRelevance
" RS5444 did not induce apoptosis but combined with paclitaxel, doubled the apoptotic index compared to that of paclitaxel."( Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1.
Copland, JA; Fujiwara, K; Haugen, BR; Klopper, JP; Kreinest, PA; Kurakata, S; Marlow, LA; Smallridge, RC; Williams, SF; Wong, AK, 2006)		0.33
" Here, we evaluate the safety and pharmacokinetics of efatutazone combined with FOLFIRI (5-fluorouracil, levo-leucovorin, and irinotecan) as second-line chemotherapy in Japanese patients with mCRC."( Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer.
Hyodo, I; Komatsu, Y; Machida, N; Ohtsu, A; Onuma, H; Sasaki, T; Yachi, Y; Yamazaki, K; Yoshino, T; Yuki, S, 2014)		0.99
"50 mg (the recommended dose [RD] of efatutazone monotherapy) twice daily in combination with FOLFIRI in a 3-9 patient cohort."( Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer.
Hyodo, I; Komatsu, Y; Machida, N; Ohtsu, A; Onuma, H; Sasaki, T; Yachi, Y; Yamazaki, K; Yoshino, T; Yuki, S, 2014)		1.02
"Efatutazone combined with FOLFIRI demonstrates an acceptable safety profile and evidence of disease stabilization in Japanese patients with mCRC."( Phase 1 study of efatutazone, a novel oral peroxisome proliferator-activated receptor gamma agonist, in combination with FOLFIRI as second-line therapy in patients with metastatic colorectal cancer.
Hyodo, I; Komatsu, Y; Machida, N; Ohtsu, A; Onuma, H; Sasaki, T; Yachi, Y; Yamazaki, K; Yoshino, T; Yuki, S, 2014)		2.18

Dosage Studied

ExcerptRelevanceReference
" Efatutazone dosing continued until disease progression or unacceptable toxicity, with measurement of efatutazone pharmacokinetics and plasma adiponectin levels."( A phase 1 study of efatutazone, an oral peroxisome proliferator-activated receptor gamma agonist, administered to patients with advanced malignancies.
Beckman, RA; Copigneaux, C; Cotarla, I; Daniel, H; Deeken, JF; Demetri, GD; Halim, AB; He, AR; Hwang, JJ; Liu, K; Malik, S; Marshall, JL; Pishvaian, MJ; Wagner, AJ; Zahir, H, 2012)		1.62
"15-mg dosing vs 22."( Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial.
Bible, KC; Brose, MS; Copland, JA; Gramza, AW; Heckman, MG; Houvras, Y; Klopper, JP; Marlow, LA; Menefee, ME; Shah, MH; Smallridge, RC; Von Roemeling, R; Wadsworth, JT, 2013)		1.83
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (1)

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Peroxisome proliferator-activated receptor gammaHomo sapiens (human)EC50 (µMol)0.00050.00000.992210.0000AID1362964; AID1409301
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (73)

Processvia Protein(s)Taxonomy
negative regulation of gene expressionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of cholesterol effluxPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
long-chain fatty acid transportPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of osteoblast differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of smooth muscle cell proliferationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of receptor signaling pathway via STATPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of low-density lipoprotein receptor activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of signaling receptor activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of gene expressionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of transforming growth factor beta receptor signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of BMP signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of MAP kinase activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of adiponectin secretionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of miRNA transcriptionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of cardiac muscle hypertrophy in response to stressPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of connective tissue replacement involved in inflammatory response wound healingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of transcription by RNA polymerase IIPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
placenta developmentPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
regulation of transcription by RNA polymerase IIPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
lipid metabolic processPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
activation of cysteine-type endopeptidase activity involved in apoptotic processPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
signal transductionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
G protein-coupled receptor signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
response to nutrientPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
regulation of blood pressurePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of gene expressionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of gene expressionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
macrophage derived foam cell differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of macrophage derived foam cell differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of cholesterol storagePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of lipid storagePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of sequestering of triglyceridePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of angiogenesisPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
monocyte differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
BMP signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of transforming growth factor beta receptor signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
epithelial cell differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cellular response to insulin stimulusPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
response to lipidPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
peroxisome proliferator activated receptor signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
glucose homeostasisPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
regulation of circadian rhythmPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
mRNA transcription by RNA polymerase IIPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
lipoprotein transportPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of blood vessel endothelial cell migrationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
innate immune responsePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cell fate commitmentPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of fat cell differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of DNA-templated transcriptionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of DNA-templated transcriptionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
retinoic acid receptor signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cell maturationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
rhythmic processPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
white fat cell differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of DNA-binding transcription factor activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
lipid homeostasisPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of type II interferon-mediated signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of SMAD protein signal transductionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
regulation of cholesterol transporter activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cellular response to low-density lipoprotein particle stimulusPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cellular response to hypoxiaPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of mitochondrial fissionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
regulation of cellular response to insulin stimulusPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of extracellular matrix assemblyPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of miRNA transcriptionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of miRNA transcriptionPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of cellular response to transforming growth factor beta stimulusPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of adipose tissue developmentPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of vascular associated smooth muscle cell proliferationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of vascular associated smooth muscle cell apoptotic processPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of vascular endothelial cell proliferationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
positive regulation of fatty acid metabolic processPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
fatty acid metabolic processPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
negative regulation of inflammatory responsePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cell differentiationPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
hormone-mediated signaling pathwayPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (28)

Processvia Protein(s)Taxonomy
transcription cis-regulatory region bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
RNA polymerase II cis-regulatory region sequence-specific DNA bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
transcription coregulator bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA-binding transcription activator activity, RNA polymerase II-specificPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
nucleic acid bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
chromatin bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
double-stranded DNA bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA-binding transcription factor activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
nuclear receptor activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
prostaglandin receptor activityPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
protein bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
zinc ion bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
enzyme bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
peptide bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
identical protein bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
sequence-specific DNA bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
nuclear retinoid X receptor bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
arachidonic acid bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA binding domain bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
LBD domain bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
alpha-actinin bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
R-SMAD bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
E-box bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
STAT family protein bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA-binding transcription factor bindingPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
DNA-binding transcription repressor activity, RNA polymerase II-specificPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (7)

Processvia Protein(s)Taxonomy
nucleusPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
nucleusPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
nucleoplasmPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
cytosolPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
intracellular membrane-bounded organellePeroxisome proliferator-activated receptor gammaHomo sapiens (human)
RNA polymerase II transcription regulator complexPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
chromatinPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
receptor complexPeroxisome proliferator-activated receptor gammaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (5)

Assay IDTitleYearJournalArticle
AID1362964Agonist activity at recombinant human GAL4-DBD fused PPARgamma LBD expressed in COS7 cells after 24 hrs by luciferase reporter gene assay2018Bioorganic & medicinal chemistry, 10-01, Volume: 26, Issue:18
Discovery of DS-6930, a potent selective PPARγ modulator. Part I: Lead identification.
AID1409301Transactivation of PPARgamma (unknown origin) transfected in human DRO cells after 24 hrs by dual luciferase reporter gene assay
AID1409305Inhibition of cologenic growth of human DRO cells at 1 nM after 2 weeks by soft agar assay relative to control
AID1362965Agonist activity at recombinant human GAL4-DBD fused PPARgamma LBD expressed in COS7 cells at 10 uM after 24 hrs by luciferase reporter gene assay relative to rosiglitazone2018Bioorganic & medicinal chemistry, 10-01, Volume: 26, Issue:18
Discovery of DS-6930, a potent selective PPARγ modulator. Part I: Lead identification.
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (24)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's6 (25.00)29.6817
2010's16 (66.67)24.3611
2020's2 (8.33)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 19.11

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index19.11 (24.57)
Research Supply Index3.40 (2.92)
Research Growth Index4.88 (4.65)
Search Engine Demand Index15.26 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (19.11)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4 (16.00%)5.53%
Reviews1 (4.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other20 (80.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (12)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Phase 1b Study of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) [NCT01199055]Phase 116 participants (Actual)Interventional2010-03-31Completed
Randomized, Active-Controlled, Open-Label Phase 2 Study of CS-7017 in Combination With FOLFIRI in Subjects With Metastatic Colorectal Cancer Who Failed First-Line Therapy [NCT00967616]Phase 2100 participants (Actual)Interventional2009-09-30Completed
A Phase 2 Study of Efatutazone, an Oral PPAR Agonist, In Combination With Paclitaxel in Patients With Advanced Anaplastic Thyroid Cancer [NCT02152137]Phase 219 participants (Actual)Interventional2014-09-30Completed
A Phase 1/2 Study of CS7017, an Oral PPARγ Agonist, in Combination With Paclitaxel in Subjects With Advanced Anaplastic Thyroid Cancer [NCT00603941]Phase 1/Phase 219 participants (Actual)Interventional2008-01-31Terminated(stopped due to Due to low enrollment, no participant had a dose limiting toxicity, therefore a maximum tolerated dose could not be established)
Phase 2 Randomized Study of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-Naïve Subjects With Metastatic Non-Small Cell Lung Cancer [NCT00806286]Phase 2111 participants (Actual)Interventional2008-12-31Completed
Extended Use of CS 7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Subjects With Cancer [NCT00881569]Phase 12 participants (Actual)Interventional2009-03-31Completed
A Phase I Dose Finding Study of an Experimental New Drug, PPARγ Agonist Taken by Mouth by Patients With Advanced or Malignancies [NCT00408434]Phase 132 participants (Actual)Interventional2006-11-30Completed
Phase 1b Study of CS-7017 in Combination With Erlotinib in Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy [NCT01199068]Phase 115 participants (Actual)Interventional2010-06-30Completed
Phase 2 Study of CS-7017 and Erlotinib in Subjects With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy [NCT01101334]Phase 290 participants (Actual)Interventional2010-03-31Completed
A Phase I Study of a Combination of the Proteosome Proliferator-Activated Receptor Gamma Agonist, CS-7017 and the Retinoid X Receptor Agonist, Bexarotene [NCT01504490]Phase 19 participants (Actual)Interventional2011-12-31Terminated(stopped due to Drug no longer available)
A Phase II Study of the Peroxisome Proliferator-Activated Receptor Gamma Agonist, Efatutazone in Patients With Previously Treated, Unresectable Myxoid Liposarcoma [NCT02249949]Phase 215 participants (Actual)Interventional2014-10-31Completed
A Randomized, Double-Blind Placebo-Controlled Phase 2 Study of CS-7017 in Colorectal Cancer Patients Who Have Achieved Disease Control Following First-Line Chemotherapy [NCT00986440]Phase 284 participants (Actual)Interventional2009-07-31Terminated(stopped due to Due to changes to the standard of care within the proposed market for CS-7017.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00408434 (5) [back to overview]Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies
NCT00408434 (5) [back to overview]Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies
NCT00408434 (5) [back to overview]Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies
NCT00408434 (5) [back to overview]Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies
NCT00408434 (5) [back to overview]Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies
NCT00603941 (4) [back to overview]Overall Progression-free Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
NCT00603941 (4) [back to overview]Overall Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
NCT00603941 (4) [back to overview]Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
NCT00603941 (4) [back to overview]Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC)
NCT00806286 (5) [back to overview]Percentage of Participants With Progression-Free Survival at 18 Weeks Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Percentage of Participants With Progression-Free Survival Based on Radiologic and Clinical Assessments and Death After Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Summary of Kaplan-Meier Analysis of Overall Survival Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Number of Participants With Best Overall Tumor Response and Objective Response Rate Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Number of Participants With Treatment-Emergent Adverse Events Related to CS-7017/Placebo Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00881569 (3) [back to overview]Treatment-Emergent Adverse Events Occurring in Participants Following Extended Use of CS-7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Participants With Cancer
NCT00881569 (3) [back to overview]Best Response Following Extended Use of CS-7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Participants With Cancer
NCT00881569 (3) [back to overview]Response/Stable Disease Duration and Time to Progression Following Extended Use of CS-7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Participants With Cancer
NCT00967616 (5) [back to overview]Median Overall Progression-Free Survival Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer
NCT00967616 (5) [back to overview]Median Overall Progression-Free Survival: Sensitivity Analysis Including Clinical Progression After Administration of CS-7017 and Irinotecan, Leucovorin, and 5-Fluorouracil After Failure of First-line Therapy of Metastatic Colorectal Cancer
NCT00967616 (5) [back to overview]Percentage of Participants With Progression-Free Survival at 16 Weeks After Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer
NCT00967616 (5) [back to overview]Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer
NCT00967616 (5) [back to overview]Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer
NCT00986440 (6) [back to overview]Number of Participants With Treatment-Emergent Adverse Events Related to Study Drug With an Incidence of ≥5% Following Use of CS-7017 Or Placebo in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy
NCT00986440 (6) [back to overview]Duration of Response for Responding Participants Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy
NCT00986440 (6) [back to overview]Best Overall Response and Objective Response Rate Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy
NCT00986440 (6) [back to overview]Percentage Rate of Progression-free Survival at 18 Weeks Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy
NCT00986440 (6) [back to overview]Percentage Rate of Progression-free Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy
NCT00986440 (6) [back to overview]Percentage Rate of Overall Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy
NCT01101334 (4) [back to overview]Analysis of Overall Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
NCT01101334 (4) [back to overview]Summary of Analysis of Progression-Free Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
NCT01101334 (4) [back to overview]Summary of Treatment-Emergent Adverse Events (TEAEs) Occurring in ≥10% of Participants Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
NCT01101334 (4) [back to overview]Overall Response Rate Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy
NCT01199055 (6) [back to overview]Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)
NCT01199055 (6) [back to overview]Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]CS-7017-Related Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group After Administration of CS-7017 and Carboplatin/Paclitaxel in Chemotherapy-naïve Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199068 (7) [back to overview]Progression-free Survival Time Following Administration of CS-7017 in Combination With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy
NCT01199068 (7) [back to overview]Best Overall Response and Response Rate Following Administration of CS-7017 in Combination With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy
NCT01199068 (7) [back to overview]CS-7017-Related Treatment-Emergent Adverse Events Occurring During the Study of Administration of CS-7017 Combined With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer Who Failed First-line Therapy
NCT01199068 (7) [back to overview]Erlotinib-Related Treatment-Emergent Adverse Events Occurring During the Study of Administration of CS-7017 Combined With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer Who Failed First-line Therapy
NCT01199068 (7) [back to overview]Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer
NCT01199068 (7) [back to overview]Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer
NCT01199068 (7) [back to overview]Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer
NCT02152137 (5) [back to overview]Confirmed Response Rate (Partial Response [PR] or Complete Response [CR]) Per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 Criteria
NCT02152137 (5) [back to overview]Duration of Confirmed Response
NCT02152137 (5) [back to overview]PFS Determined Based on RECIST 1.1 Criteria
NCT02152137 (5) [back to overview]Overall Survival
NCT02152137 (5) [back to overview]Number of Patients Experiencing at Least One Grade 3+ Adverse Event Using CTCAE Version 4.0
NCT02249949 (4) [back to overview]Confirmed Overall Response Rate Per the RECIST 1.1 Criteria
NCT02249949 (4) [back to overview]Overall Survival
NCT02249949 (4) [back to overview]Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
NCT02249949 (4) [back to overview]Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0

Summary of Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies

Area under the plasma/serum drug concentration-time curve for dosing interval (AUC[0-tau]), computed using the linear trapezoidal rule and area under the plasma/serum drug concentration-time curve from 0 to last time point above the quantification limit (AUC[0-t]) calculated using the linear trapezoidal rule were assessed. (NCT00408434)
Timeframe: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.

,,,,,,
Interventionng*h/ml (Mean)
AUC(0-tau)AUC(0-12)
CS-7017 0.10 mg23.0532.96
CS-7017 0.15 mg32.0544.14
CS-7017 0.25 mg68.3391.24
CS-7017 0.35 mg59.7280.80
CS-7017 0.50 mg159.2220.9
CS-7017 0.75 mg159.14214.38
CS-7017 1.15 mg256.3356.8

[back to top]

Best Overall Tumor Response Following Administration of CS-7017 in Participants With Advanced or Metastatic Malignancies

Complete response (CR) was defined as a disappearance of all target lesions, partial response (PR) was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions). Objective response rate was defined as the sum of all CRs and PRs. (NCT00408434)
Timeframe: Baseline up to at least 2 cycles (each cycle was 3 weeks), up to 2 years 5 months

,,,,,,,
InterventionParticipants (Count of Participants)
Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)Objective response rate (CR+PR)
CS-7017 0.10 mg00330
CS-7017 0.15 mg00210
CS-7017 0.25 mg00040
CS-7017 0.35 mg00120
CS-7017 0.50 mg00410
CS-7017 0.75 mg01111
CS-7017 1.15 mg00120
CS-7017 All Participants0112141

[back to top]

Summary of Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies

Tmax was defined as time of maximum plasma concentration. (NCT00408434)
Timeframe: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.

Interventionhour (Mean)
CS-7017 0.10 mg3.00
CS-7017 0.15 mg2.00
CS-7017 0.25 mg1.58
CS-7017 0.35 mg3.00
CS-7017 0.50 mg2.00
CS-7017 0.75 mg3.00
CS-7017 1.15 mg2.50

[back to top]

Summary of Pharmacokinetic Parameter Terminal Elimination Half-life (t1/2) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies

(NCT00408434)
Timeframe: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.

Interventionhour (Mean)
CS-7017 0.10 mg8.51
CS-7017 0.15 mg13.78
CS-7017 0.25 mg11.48
CS-7017 0.35 mg12.49
CS-7017 0.50 mg5.74
CS-7017 0.75 mg9.08
CS-7017 1.15 mg11.66

[back to top]

Summary of Pharmacokinetic Parameter Observed Maximum Plasma Concentration (Cmax) of Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 in Patients With Advanced or Metastatic Malignancies

Cmax was defined as observed maximum plasma concentration. (NCT00408434)
Timeframe: Day 1 of Cycles 1 and 2: predose, 0.5, 1, 2, 3, 4, 6, and 10 hours postdose; and predose on Day 8 and 15 of Cycle 1.

Interventionng/ml (Mean)
CS-7017 0.10 mg4.21
CS-7017 0.15 mg5.76
CS-7017 0.25 mg12.19
CS-7017 0.35 mg12.26
CS-7017 0.50 mg26.92
CS-7017 0.75 mg27.64
CS-7017 1.15 mg44.73

[back to top]

Overall Progression-free Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)

Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions. (NCT00603941)
Timeframe: From baseline up to disease progression or death, up to approximately 2 years postdose

Interventiondays (Median)
All Patients55.5

[back to top]

Overall Survival in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)

Overall survival (OS) was defined as the time from the date enrollment to the date of death. (NCT00603941)
Timeframe: From baseline up to date of death, up to approximately 2 years postdose

Interventiondays (Median)
All Patients130.0

[back to top]

Best Overall Response in Participants After a Dosage of CS-7017 Administered Twice Daily in Combination With Paclitaxel Administered Once Every 3 Weeks to Participants With Advanced Anaplastic Thyroid Cancer (ATC)

The best overall response was the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the subject withdraws from the study. If there is no tumor assessment after the date of enrollment, the best overall response is classified as Unknown. (NCT00603941)
Timeframe: From baseline up to disease progression or the development of unacceptable toxicity, up to approximately 2 years postdose

InterventionParticipants (Count of Participants)
Confirmed complete response (CR)Confirmed partial response (PR)Objective response (confirmed CR + PR)Stable diseaseProgressive diseaseUnknown
All Patients011842

[back to top]

Number of Participants With Treatment-Emergent Adverse Events, Summarized by Worst CTCAE Grade (≥3) and Preferred Term After Administration of CS-7017 Combined With Paclitaxel Administered to Participants With Advanced Anaplastic Thyroid Cancer (ATC)

Treatment-emergent adverse events (TEAEs) are defined as adverse events that started or worsened after the first dose of any study drug (after Day 1 or first day of CS-7017 monotherapy) but adverse events occurring more than 30 days after the last dose are not considered TEAEs unless also considered to be related (possibly, probably, or definitely) to study drug. (NCT00603941)
Timeframe: From baseline up to 30 days after last dose, up to approximately 2 years

,,
InterventionParticipants (Count of Participants)
Any Severe TEAE of Grade ≥3AnaemiaDysphagiaDisease progressionAnaphylatic reactionPneumoniaSeptic shockNeutrophil count decreasedLoss of consciousnessDyspnoea
Cohort 1; 0.15 mg CS-70173012001000
Cohort 2; 0.30 mg CS-70175100010101
Cohort 3; 0.50 mg CS-70172000100010

[back to top]

Percentage of Participants With Progression-Free Survival at 18 Weeks Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (based upon radiographic tumor assessments) or death. As per Response Evaluation Criteria for Solid Tumors v1.0, disease progression was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. (NCT00806286)
Timeframe: 18 weeks postdose

Interventionpercentage of participants (Number)
CS7017+Carboplatin+Paclitaxel40.2
CS7017-matching Placebo+Carboplatin+Paclitaxel63.3

[back to top]

Percentage of Participants With Progression-Free Survival Based on Radiologic and Clinical Assessments and Death After Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (based upon radiographic tumor assessments) or death. Disease progression was determined in accordance with the RECIST version 1.0 criteria. (NCT00806286)
Timeframe: 18 weeks postdose

Interventionpercentage of participants (Number)
CS7017+Carboplatin+Paclitaxel37.9
CS7017-matching Placebo+Carboplatin+Paclitaxel63.3

[back to top]

Summary of Kaplan-Meier Analysis of Overall Survival Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

Overall survival (OS) is defined as the time from randomization to the date of death resulting from any cause. (NCT00806286)
Timeframe: Baseline to date of death, up to approximately 2 years postdose

Interventiondays (Median)
CS7017+Carboplatin+Paclitaxel244.0
CS7017-matching Placebo+Carboplatin+Paclitaxel292.0

[back to top]

Number of Participants With Best Overall Tumor Response and Objective Response Rate Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

As per Response Evaluation Criteria for Solid Tumors v1.0, the best overall response was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. Objective response rate (ORR) was defined as CR + PR. (NCT00806286)
Timeframe: Baseline to disease progression, death, or withdrawal from study, up to approximately 2 years postdose

,
InterventionParticipants (Count of Participants)
Confirmed complete response (CR)Confirmed partial response (PR)Objective response (Confirmed CR+PR)Stable disease (SD)Progressive disease (PD)UnknownBest Objective Response of SD or Better
CS7017-matching Placebo+Carboplatin+Paclitaxel01616185742
CS7017+Carboplatin+Paclitaxel011111117829

[back to top] [back to top]

Treatment-Emergent Adverse Events Occurring in Participants Following Extended Use of CS-7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Participants With Cancer

Adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0. AE intensity was assessed according to the following scale: Mild (Grade 1), Awareness of sign or symptom, but easily tolerated, ie, does not interfere with subject's usual function; Moderate (Grade 2), Discomfort enough to cause interference with usual activity; Severe (Grade 3), Incapacitating with inability to work or do usual activity, ie, interferes significantly with participant's usual function. Severe (Grade 3) AEs indicate worse outcomes. (NCT00881569)
Timeframe: Baseline up to 30 days after last dose, up to 2 years 6 months

,
InterventionParticipants (Count of Participants)
Grade 3 HypercholesterolemiaGrade 1-2 HypertriglyceridemiaGrade 1 FatigueGrade 3 AnaemiaGrade 1-2 AnaemiaGrade 1 RegurgitationGrade 1 Tongue paralysis
CS-7017 0.50 mg BID0001111
CS-7017 0.75 mg BID1110000

[back to top]

Best Response Following Extended Use of CS-7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Participants With Cancer

At each evaluation, the participant's status was assessed as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD); the best response was then identified. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions). (NCT00881569)
Timeframe: From baseline and every 6 weeks postdose, up to 2 years 6 months

,
InterventionParticipants (Count of Participants)
Partial response (PR)Stable disease (SD)
CS-7017 0.50 mg BID01
CS-7017 0.75 mg BID10

[back to top]

Response/Stable Disease Duration and Time to Progression Following Extended Use of CS-7017 Upon Completion of Participation in a Clinical Study of CS-7017 in Participants With Cancer

Duration of response was to be calculated as the date of progression minus the earliest date of complete response (CR) or partial response (PR), plus 1. The earliest date of CR or PR was to be taken from the earlier study (CS7017-A-U102). If any participant entered the study with stable disease (SD), then the duration of SD was to be calculated as the date of progression minus the date of first dose, plus 1. Time to progression was to be calculated as the date of progression minus the date of first dose of study medication in the earlier study, plus 1. (NCT00881569)
Timeframe: Baseline and every 6 weeks postdose, up to 2 years 6 months

,
Interventiondays (Number)
Response durationTime to progressionStable disease duration
CS-7017 0.50 mg BIDNA337337
CS-7017 0.75 mg BID441686NA

[back to top]

Median Overall Progression-Free Survival Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

Progression-free survival (PFS) was defined as the time from randomization until the first objective evidence of disease progression or death from any cause. (NCT00967616)
Timeframe: Baseline to approximately 3 years postdose

Interventionmonths (Median)
FOLFIRI4.2
CS7017 + FOLFIRI4.4

[back to top]

Median Overall Progression-Free Survival: Sensitivity Analysis Including Clinical Progression After Administration of CS-7017 and Irinotecan, Leucovorin, and 5-Fluorouracil After Failure of First-line Therapy of Metastatic Colorectal Cancer

Progression-free survival (PFS) was defined as the time from randomization to the date of the first objective documentation of progressive disease (PD) or death resulting from any cause, whichever came first. The sensitivity analysis included clinical progression as an event. (NCT00967616)
Timeframe: Baseline to approximately 3 years postdose

Interventionmonths (Median)
FOLFIRI4.2
CS7017 + FOLFIRI4.4

[back to top]

Percentage of Participants With Progression-Free Survival at 16 Weeks After Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (5-FU) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

Progression-free survival (PFS) was defined as the time from randomization until the first objective evidence of disease progression or death from any cause. (NCT00967616)
Timeframe: Baseline to 16 weeks postdose

Interventionpercentage of participants (Number)
FOLFIRI66.7
CS7017 + FOLFIRI59.7

[back to top]

Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

As per Response Evaluation Criteria for Solid Tumors v1.0, best overall response was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. Objective response rate (ORR) was defined as CR + PR. If there is no tumor assessment after the first dose of study drug, the best overall response is classified as Inevaluable. (NCT00967616)
Timeframe: Baseline to approximately 3 years postdose

,
InterventionParticipants (Count of Participants)
Confirmed CRConfirmed PRObjective response (confirmed CR+PR)Stable diseaseProgressive diseaseInevaluableBest overall response of SD or better
CS7017 + FOLFIRI010101881230
FOLFIRI0772910238

[back to top]

Treatment-Emergent Adverse Events Occurring in ≥10% of Participants Following Administration of CS-7017 Combined With Irinotecan, Leucovorin, and 5-Fluorouracil (FOLFIRI) After Failure of First-line Therapy in Treatment of Metastatic Colorectal Cancer

An adverse event (AE) >30 days after last dose of study drug was not included as a treatment-emergent adverse events (TEAE) unless considered related to treatment. (NCT00967616)
Timeframe: Baseline to 30 days post last dose, up to approximately 3 years

,
InterventionParticipants (Count of Participants)
Any TEAEBlood and Lymphatic System DisordersAnaemiaFebrile neutropeniaLeukopeniaNeutropeniaThrombocytopeniaEye DisordersGastrointestinal DisordersAbdominal painAbdominal pain upperAphthous stomatitisConstipationDiarrheaNauseaVomitingGeneral Disorders & Administration Site ConditionsAstheniaFace EdemaFatigueMucosal inflammationEdema peripheralPyrexiaInfections & InfestationsInfluenzaInjury, Poisoning, and Procedural ComplicationsInvestigationsWeight decreasedWeight increasedMetabolism and Nutrition DisordersDecreased appetiteDehydrationHypokalaemiaMusculoskeletal and Connective Tissue DisordersPain in extremityBack painNervous System DisordersDizzinessHeadachePsychiatric DisordersRenal and Urinary DisordersReproductive System and Breast DisordersRespiratory, Thoracic, and Mediastinal DisordersCoughDyspneaSkin and Subcutaneous Tissue DisordersAlopeciaVascular Disorders
CS7017 + FOLFIRI5042357113398492012133039244314915734102116286202817461263143511931956201010
FOLFIRI50241600102147176593336333922091375215416120312374184617531065175721118

[back to top] [back to top]

Duration of Response for Responding Participants Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy

Duration of response was defined for participants with confirmed CR or PR and confirmed and unconfirmed CR or PR as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease. Duration of SD was defined for participants whose best response was SD as the time from the randomization date to the date of the first documentation of progressive disease. Duration of response was estimated using Kaplan Meier methods. (NCT00986440)
Timeframe: From the date of first objective response (confirmed and unconfirmed CR or PR) to date of progressive disease, up to 3 years 3 months

,
Interventionweeks (Mean)
Duration of response (confirmed responses)Duration of response (confirmed and unconfirmed)Duration of stable disease
CS-7017 0.5 mg33.5733.5726.16
Placebo37.8615.9622.52

[back to top]

Best Overall Response and Objective Response Rate Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy

The best overall response was defined as the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdrew from the study. If there was no tumor assessment after the first dose of study drug, the best overall response was classified as Inevaluable. Based on RECIST v1.0, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions. (NCT00986440)
Timeframe: From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to approximately 3 years 3 months

,
InterventionParticipants (Count of Participants)
Confirmed CRConfirmed PRObjective response (confirmed CR+PR)Unconfirmed CRUnconfirmed PRStable diseaseProgressive diseaseInevaluableBest overall response of SD or better
CS-7017 0.5 mg516001020316
Placebo10103827312

[back to top]

Percentage Rate of Progression-free Survival at 18 Weeks Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy

Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions. (NCT00986440)
Timeframe: 18 weeks postdose

Interventionpercentage of participants (Number)
CS-7017 0.5 mg39.86
Placebo25.00

[back to top]

Percentage Rate of Progression-free Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy

Progression-free survival (PFS) was defined as the time from enrollment to the date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as at least a 20% increase in the sum of diameters of target lesions. (NCT00986440)
Timeframe: At 12, 24, and 30 weeks postdose

,
Interventionpercentage of participants (Number)
Progression-free survival at 12 weeksProgression-free survival at 24 weeksProgression-free survival at 30 weeks
CS-7017 0.5 mg62.029.929.9
Placebo47.515.012.5

[back to top]

Percentage Rate of Overall Survival Following Use of CS-7017 in Colorectal Cancer Participants Who Have Achieved Disease Control Following First-Line Chemotherapy

Overall survival (OS) was defined as the time from the date of enrollment to the date of death and assessed by Kaplan Meier analysis. (NCT00986440)
Timeframe: At 3, 6, 9, and 12 months postdose

,
Interventionpercentage of participants (Number)
Overall survival rate at 3 monthsOverall survival rate at 6 monthsOverall survival rate at 9 monthsOverall survival rate at 12 months
CS-7017 0.5 mg100.087.274.468.4
Placebo92.985.575.255.4

[back to top]

Analysis of Overall Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy

Overall survival (OS) was defined as the time from randomization until death from any cause. (NCT01101334)
Timeframe: Baseline to death, up to approximately 2.5 years

Interventionmonths (Median)
CS-7017 Plus Erlotinib7.6
Erlotinib11.4

[back to top]

Summary of Analysis of Progression-Free Survival Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy

Progression-free survival (PFS) was defined as the time from randomization date of the first objective documentation of disease progression or death resulting from any cause, whichever comes first. (NCT01101334)
Timeframe: Baseline to disease progression or death, up to approximately 2.5 years

Interventionmonths (Median)
CS-7017 Plus Erlotinib4.1
Erlotinib3.0

[back to top]

Summary of Treatment-Emergent Adverse Events (TEAEs) Occurring in ≥10% of Participants Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy

A treatment-emergent adverse event (TEAE) was defined as an adverse event that had an onset date on or after the first dose of CS-7017 or erlotinib up to and including 30 days after the last dose of any study drug, or worsened in severity after the first dose of CS-7017 or erlotinib relative to the pre-treatment state. (NCT01101334)
Timeframe: Baseline to 30 days after last dose, up to approximately 2.5 years

,
InterventionParticipants (Count of Participants)
Any TEAEBlood and Lymphatic System DisordersAnaemiaCardiac DisordersEye DisordersGastrointestinal DisordersConstipationDiarrheaNauseaStomatitisGeneral Disorders & Administration Site ConditionsAstheniaDisease progressionFace edemaFatigueNoncardiac chest painEdema peripheralPyrexiaInfections and InfestationsInvestigationsWeight increasedMetabolism and Nutrition DisordersDecreased appetiteHypokalemiaMusculoskeletal and Connective Tissue DisordersPain in extremityNervous System DisordersDizzinessHeadachePsychiatric DisordersRespiratory, Thoracic, and Mediastinal DisodersCoughDyspneaPleural effusionSkin and Subcutaneous Tissue DisordersAlopeciaDermatitis acneiformDry skinPruritusRashSwelling faceVascular Disorders
CS-7017 Plus Erlotinib44181678271018564198109517913157271871571555625591033515591151
Erlotinib4343232531976198505213161211510110062151737030097111515

[back to top]

Overall Response Rate Following Administration of CS-7017 and Erlotinib in Participants With Advanced Non-Small Cell Lung Cancer Who Failed First Line Therapy

The overall response rate (ORR) was defined as the proportion of participants who achieved best overall response of complete response (CR) or partial response (PR); ORR = CR + PR. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions. (NCT01101334)
Timeframe: Baseline to disease progression or death, up to approximately 2.5 years

InterventionParticipants (Count of Participants)
CS-7017 Plus Erlotinib9
Erlotinib9

[back to top]

Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug. (NCT01199055)
Timeframe: Baseline to end of Cycle 1, with each treatment cycle being 3 weeks

,,
InterventionParticipants (Count of Participants)
At least one TEAEBlood and lymphatic system disordersNeutropeniaAnaemiaMetabolism and Nutrition DisordersDecreased appetiteNervous System DisordersNeuropathy peripheralRespiratory, Thoracic and Mediastinal DisordersPleural effusionGastrointestinal DisordersNauseaSkin and Subcutaneous Tissue DisordersAlopeciaPruritusMusculoskeletal and Connective Tissue DisordersMyalgiaAthralgiaGeneral Disorders & Administration Site ConditionsFatigueInvestigationsWeight increased
CS-7017 0.25 mg BID; Initial Portion3330001010222203213300
CS-7017 0.50 mg BID; Additional Portion9875664444618817605187
CS-7017 0.50 mg BID; Initial Portion4220211100112122021022

[back to top]

Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)

The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses from the start of treatment until the participant withdraws from the study. Participants who did not have a tumor assessment, the best overall response is Not Evaluable (NE). The response rate was defined as the proportion of participants with a best overall response of CR or PR, ie, [confirmed and unconfirmed, (CR + PR) / number of participants]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions, PR was defined as ≥30% decrease in the sum of diameters of target lesions, PD was defined as ≥20 increase in the smallest sum of diameters, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT01199055)
Timeframe: Baseline up to Week 18 postdose

,,,,
InterventionParticipants (Count of Participants)
Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)Not evaluable (NE)MissingResponse rate (CR + PR)
CS-7017 0.25 mg BID; Initial Portion0012000
CS-7017 0.50 mg BID; Additional Portion0422004
CS-7017 0.50 mg BID; Initial Portion0201002
CS71017 0.5 mg BID; Initial and Additional Portion0623006
Overall0635006

[back to top]

Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D). (NCT01199055)
Timeframe: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose

,,
Interventionh (Median)
Cycle 1, Week 1: TmaxCycle 2, Week 4: Tmax,ss
CS-7017 0.25 mg BID; Initial Portion3.903.17
CS-7017 0.50 mg BID; Additional Portion5.953.88
CS-7017 0.50 mg BID; Initial Portion3.003.98

[back to top]

Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D). (NCT01199055)
Timeframe: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose

,,
Interventionng/mL (Mean)
Cycle 1, Week 1: CmaxCycle 2, Week 4: Cmax,ss
CS-7017 0.25 mg BID; Initial Portion8.9013.63
CS-7017 0.50 mg BID; Additional Portion14.5439.58
CS-7017 0.50 mg BID; Initial Portion15.9833.83

[back to top]

Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

The area under the concentration versus time curve during dosing interval (AUCtau) and up to the last quantifiable time (AUClast) of geometric means of CS-7017 are reported at selected cycles (C) and days (D). (NCT01199055)
Timeframe: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose

,,
Interventionng*h/mL (Mean)
Cycle 1, Week 1: AUCtauCycle 1, Week 1: AUClastCycle 2, Week 4: AUCtauCycle 2, Week 4: AUClast
CS-7017 0.25 mg BID; Initial Portion70.6649.57132.4795.94
CS-7017 0.50 mg BID; Additional Portion203.9981.54400.89268.00
CS-7017 0.50 mg BID; Initial Portion209.3387.23345.56240.61

[back to top] [back to top]

Progression-free Survival Time Following Administration of CS-7017 in Combination With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy

Progression-free survival (PFS) was defined as the time from randomization to the date of the first objective documentation of progressive disease (PD) or death resulting from any cause, whichever came first. (NCT01199068)
Timeframe: From randomization to PD or death, up to approximately 1.5 years

Interventiondays (Median)
CS-7017 0.50 mg BID; Additional Portion125
CS-7017 0.50 mg BID; Initial + Additional Portions82
Overall84

[back to top]

Best Overall Response and Response Rate Following Administration of CS-7017 in Combination With Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) Who Failed First-line Therapy

"As per Response Evaluation Criteria for Solid Tumors v1.1, best overall response was characterized as complete response (CR) defined as disappearance of all target lesions, partial response (PR) defined as~≥30% decrease in the sum of diameters of target lesions, progressive disease (PD) defined as ≥20% increase in the sum of diameters of target lesions, and stable disease (SD) defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Response rate was defined as CR + PR." (NCT01199068)
Timeframe: From screening and after completion of every 2 cycles (6 weeks) until disease progression, withdrawal of consent, death, or loss to follow-up, up to approximately 1.5 years

,,,,
InterventionParticipants (Count of Participants)
Partial response (PR)Stable disease (SD)Progressive disesae (PD)Response rate (CR+PR)
CS-7017 0.25 mg BID; Initial Portion0200
CS-7017 0.50 mg BID; Additional Portion5115
CS-7017 0.50 mg BID; Initial + Additional Portions5235
CS-7017 0.50 mg BID; Initial Portion0120
Overall5435

[back to top] [back to top] [back to top]

Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer

After the first CS-7017 administration, area under the concentration-time curve from zero to the last quantifiable concentration (AUClast) and area under the concentration-time curve during dosing interval (AUCtau) were assessed. (NCT01199068)
Timeframe: Cycle 1, Week 1 and Cycle 2, Week 4

,
Interventionng*h/mL (Mean)
Cycle 1, Week 1: AUClastCycle 1, Week 1: AUCtauCycle 2, Week 4: AUClastCycle 2, Week 4: AUCtau
CS-7017 0.25 mg BID; Initial Portion50.897.2124174
CS-7017 0.50 mg BID; Initial + Additional Portions148205212307

[back to top]

Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer

After the first CS-7017 administration, observed serum concentration (Cmax) and observed serum concentration at steady state (Cmax,ss) were assessed. (NCT01199068)
Timeframe: Cycle 1, Week 1 and Cycle 2, Week 4

,
Interventionng/mL (Mean)
Cycle 1, Week 1: CmaxCycle 2, Week 4: Cmax,ss
CS-7017 0.25 mg BID; Initial Portion9.9818.9
CS-7017 0.50 mg BID; Initial + Additional Portions25.132.4

[back to top]

Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Serum Free Form of CS-7017 (R-150033) After CS-7017 and Erlotinib in Participants With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer

After the first CS-7017 administration, time of maximum plasma concentration (Tmax) and time of maximum plasma concentration at steady state (Tmax,ss) were assessed. (NCT01199068)
Timeframe: Cycle 1, Week 1 and Cycle 2, Week 4

,
Interventionh (Median)
Cycle 1, Week 1: TmaxCycle 2, Week 4: Tmax,ss
CS-7017 0.25 mg BID; Initial Portion3.003.50
CS-7017 0.50 mg BID; Initial + Additional Portions3.003.00

[back to top]

Confirmed Response Rate (Partial Response [PR] or Complete Response [CR]) Per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 Criteria

The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. (NCT02152137)
Timeframe: Up to 24 weeks

Interventionpercentage of patients (Number)
Efatutazone Dihydrochloride, Paclitaxel13

[back to top]

Duration of Confirmed Response

Duration of response is defined for all evaluable patients who have achieved a confirmed response as the date at which the patient's objective status is first noted to be a CR or PR to the earliest date progression (PD) is documented. The distribution of duration of response will be estimated using the method of Kaplan-Meier. (CR: Disappearance of all evidence of disease, PR: Regression of measurable disease and no new sites, PD: Any new lesion or increase by ≥50% of previously involved sites from nadir). (NCT02152137)
Timeframe: The time from the first documented date of confirmed response (CR or PR) to date at which progression is first documented, assessed up to 5 years

Interventionmonths (Number)
Patient #1Patient #2
Efatutazone Dihydrochloride, Paclitaxel12.23.2

[back to top]

PFS Determined Based on RECIST 1.1 Criteria

Progression free survival (PFS) is defined as the time from the date of registration to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT02152137)
Timeframe: The time from study entry to the first of either disease progression or death from any cause, assessed up to 5 years

Interventionmonths (Median)
Efatutazone Dihydrochloride, Paclitaxel2.5

[back to top]

Overall Survival

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT02152137)
Timeframe: Time from study entry to death from any cause, assessed up to 5 years

Interventionmonths (Median)
Efatutazone Dihydrochloride, Paclitaxel6.6

[back to top]

Number of Patients Experiencing at Least One Grade 3+ Adverse Event Using CTCAE Version 4.0

The number of patients who experienced at least one grade 3 or higher adverse event is reported below. (NCT02152137)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Efatutazone Dihydrochloride, Paclitaxel13

[back to top]

Confirmed Overall Response Rate Per the RECIST 1.1 Criteria

The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. (NCT02249949)
Timeframe: Up to 24 weeks (8 cycles)

Interventionpercentage of patients (Number)
Efatutazone Dihydrochloride0

[back to top]

Overall Survival

Overall survival time is defined as the time from study entry to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT02249949)
Timeframe: Time from study entry to death from any cause, assessed up to 5 years

Interventionmonths (Median)
Efatutazone Dihydrochloride8.6

[back to top]

Progression Free Survival (PFS) Determined Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Progression free survival (PFS) is defined as the time from study entry to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT02249949)
Timeframe: Time from study entry to the first of either disease progression or death from any cause, assessed up to 5 years

Interventionmonths (Median)
Efatutazone Dihydrochloride1.4

[back to top]

Incidence of Grade 3+ Adverse Events Summarized Using Common Terminology Criteria for Adverse Events Version 4.0

Incidence of grade 3+ adverse events summarized using Common Terminology Criteria for Adverse Events version 4.0: The frequency and percentage of grade 3+ adverse events will be estimated (NCT02249949)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
at least one grade 3 or worse AEat least one grade 4 or worse AE
Efatutazone Dihydrochloride63

[back to top]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
fluorouracil
Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.		3.4811nucleobase analogue;
organofluorine compound		antimetabolite;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
radiosensitizing agent;
xenobiotic
troglitazone
Troglitazone: A chroman and thiazolidinedione derivative that acts as a PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS (PPAR) agonist. It was formerly used in the treatment of TYPE 2 DIABETES MELLITUS, but has been withdrawn due to hepatotoxicity.		2.0310chromanes;
thiazolidinone		anticoagulant;
anticonvulsant;
antineoplastic agent;
antioxidant;
EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
hypoglycemic agent;
platelet aggregation inhibitor;
vasodilator agent
quinazolines
Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.		2.5220azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinazolines
camptothecin
NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source		3.4811delta-lactone;
pyranoindolizinoquinoline;
quinoline alkaloid;
tertiary alcohol		antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
genotoxin;
plant metabolite
azoxymethane
Azoxymethane: A potent carcinogen and neurotoxic compound. It is particularly effective in inducing colon carcinomas.		2.0410
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		8.8421taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
rosiglitazone
[no description available]		2.1710aminopyridine;
thiazolidinediones		EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
insulin-sensitizing drug
gefitinib
[no description available]		2.5720aromatic ether;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
quinazolines;
secondary amino compound;
tertiary amino compound		antineoplastic agent;
epidermal growth factor receptor antagonist
erlotinib hydrochloride
[no description available]		2.110hydrochloride;
terminal acetylenic compound		antineoplastic agent;
protein kinase inhibitor
t0901317
T0901317: an LXRalpha and LXRbeta agonist		7.1710
prostaglandin d2
Prostaglandin D2: The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.. prostaglandin D2 : A member of the class of prostaglandins D that is prosta-5,13-dien-1-oic acid substituted by hydroxy groups at positions 9 and 15 and an oxo group at position 11 (the 5Z,9alpha,13E,15S- stereoisomer).		2.1710prostaglandins Dhuman metabolite;
mouse metabolite
stilbenes
Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.. trans-stilbene : The trans-isomer of stilbene.		3.2510stilbene
rivoglitazone
rivoglitazone: structure in first source		2.1710
fosbretabulin
fosbretabulin: a microtubule destabilizing agent isolated from Combretum caffrum; structure in first source		3.2510
15-deoxyprostaglandin j2
15-deoxyprostaglandin J2: 15d-PGJ2 abbreviation is also used for 15-deoxy-delta(12,14)PGJ2		2.1710
epidermal growth factor
Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.		7.110
levoleucovorin
Levoleucovorin: A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.. (6S)-5-formyltetrahydrofolic acid : The pharmacologically active (6S)-stereoisomer of 5-formyltetrahydrofolic acid.		3.48115-formyltetrahydrofolic acidantineoplastic agent;
metabolite
ConditionIndicatedRelationship StrengthStudiesTrials
Disease Exacerbation
[description not available]		02.8130
ER-Negative PR-Negative HER2-Negative Breast Cancer
[description not available]		02.3110
Cancer of Lung
[description not available]		02.8530
Metastase
[description not available]		03.9521
Invasiveness, Neoplasm
[description not available]		02.8530
Lung Neoplasms
Tumors or cancer of the LUNG.		02.8530
Neoplasm Metastasis
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.		03.9521
Triple Negative Breast Neoplasms
Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.		02.3110
Anterior Cervical Pain
[description not available]		03.0610
Thyroid Cancer, Anaplastic
[description not available]		04.8221
Dysphagia
[description not available]		03.0610
Breathlessness
[description not available]		03.0610
Breathing Sounds
[description not available]		03.0610
Cancer of the Thyroid
[description not available]		05.4651
Hoarseness
An unnaturally deep or rough quality of voice.		03.0610
Deglutition Disorders
Difficulty in SWALLOWING which may result from neuromuscular disorder or mechanical obstruction. Dysphagia is classified into two distinct types: oropharyngeal dysphagia due to malfunction of the PHARYNX and UPPER ESOPHAGEAL SPHINCTER; and esophageal dysphagia due to malfunction of the ESOPHAGUS.		03.0610
Dyspnea
Difficult or labored breathing.		03.0610
Respiratory Sounds
Noises, normal and abnormal, heard on auscultation over any part of the RESPIRATORY TRACT.		03.0610
Thyroid Neoplasms
Tumors or cancer of the THYROID GLAND.		17.4651
Neck Pain
Discomfort or more intense forms of pain that are localized to the cervical region. This term generally refers to pain in the posterior or lateral regions of the neck.		03.0610
Thyroid Carcinoma, Anaplastic
An aggressive THYROID GLAND malignancy which generally occurs in IODINE-deficient areas in people with previous thyroid pathology such as GOITER. It is associated with CELL DEDIFFERENTIATION of THYROID CARCINOMA (e.g., FOLLICULAR THYROID CARCINOMA; PAPILLARY THYROID CANCER). Typical initial presentation is a rapidly growing neck mass which upon metastasis is associated with DYSPHAGIA; NECK PAIN; bone pain; DYSPNEA; and NEUROLOGIC DEFICITS.		04.8221
Lung Adenocarcinoma
[description not available]		02.5720
Adenocarcinoma, Basal Cell
[description not available]		02.1510
Adenocarcinoma of Lung
A carcinoma originating in the lung and the most common lung cancer type in never-smokers. Malignant cells exhibit distinct features such as glandular epithelial, or tubular morphology. Mutations in KRAS, EGFR, BRAF, and ERBB2 genes are associated with this cancer.		02.5720
Adenocarcinoma
A malignant epithelial tumor with a glandular organization.		07.1510
Breast Cancer
[description not available]		02.5820
Atypical Ductal Hyperplasia
[description not available]		02.1710
Breast Neoplasms
Tumors or cancer of the human BREAST.		02.5820
Carcinoma, Intraductal, Noninfiltrating
A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.		02.1710
Condition, Preneoplastic
[description not available]		02.5220
Experimental Mammary Neoplasms
[description not available]		02.830
Precancerous Conditions
Pathological conditions that tend eventually to become malignant.		02.5220
Esophageal Squamous Cell Carcinoma
A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.		02.110
Carcinoma, Epidermoid
[description not available]		02.110
Cancer of Esophagus
[description not available]		02.110
Carcinoma, Squamous Cell
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)		02.110
Esophageal Neoplasms
Tumors or cancer of the ESOPHAGUS.		02.110
Colorectal Cancer
[description not available]		08.8521
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.		16.9242
Carcinoma, Non-Small Cell Lung
[description not available]		02.110
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		14.110
Benign Neoplasms
[description not available]		05.3522
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		18.9544
Cell Transformation, Neoplastic
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.		02.0410
Cancer of Colon
[description not available]		02.0410
Colonic Neoplasms
Tumors or cancer of the COLON.		02.0410
Carcinoma, Anaplastic
[description not available]		02.0510
Carcinoma
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for cancer.		02.0510