Compounds > trabedersen
Page last updated: 2024-10-15

trabedersen

Description

Trabedersen: TGF-beta2 inhibitor antisense therapeutic for tumor treatment [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID132472120
MeSH IDM0517451

Synonyms (7)

Synonym
ap-2-09
unii-98oyr854ny
trabedersen [inn:ban]
98oyr854ny ,
trabedersen
925681-61-4
dna, d(p-thio)(c-g-g-c-a-t-g-t-c-t-a-t-t-t-t-g-t-a)

Research Excerpts

Overview

Trabedersen is a phosphorothioate antisense oligodeoxynucleotide specific for human TGF-β2 mRNA. It was successfully tested in a randomized, active-controlled phase IIb clinical study in patients with high-grade glioma.

ExcerptReference
"Trabedersen (AP 12009) is a phosphorothioate antisense oligodeoxynucleotide specific for human TGF-β2 mRNA and was successfully tested in a randomized, active-controlled phase IIb clinical study in patients with high-grade glioma."( Transforming growth factor-beta 2 gene silencing with trabedersen (AP 12009) in pancreatic cancer.
Geissler, EK; Jaschinski, F; Kielmanowicz, M; Lang, SA; Moser, C; Schlingensiepen, KH; Schlitt, HJ; Schneider, A, 2011)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (11)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's3 (27.27)29.6817
2010's8 (72.73)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (8.33%)5.53%
Reviews4 (33.33%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other7 (58.33%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (5)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Efficacy and Safety of AP 12009 in Adult Patients With Recurrent or Refractory Anaplastic Astrocytoma or Secondary Glioblastoma as Compared to Standard Chemotherapy Treatment: A Randomized, Actively Controlled, Open Label Clinical Phase III Study.[NCT00761280]Phase 327 participants (Actual)Interventional2008-12-31Terminated(stopped due to Unable to recruit the projected patient number. All analyses are descriptive, only.)
An Open-Label, Multicenter Dose-Escalation Study to Evaluate the Safety and Tolerability of AP 12009 (Trabedersen), Administered Intravenously in Patients With Advanced Tumors Known to Overproduce TGF-β2.[NCT00844064]Phase 162 participants (Actual)Interventional2005-01-31Completed
Multi-national, Open-label, Active-controlled, Randomized Dose-finding Study to Evaluate Efficacy of 2 Doses of AP 12009 in Recurrent Glioma, Administered Intratumorally as Continuous High-flow Microperfusion Over 7 Days Every Other Week[NCT00431561]Phase 2141 participants (Actual)Interventional2003-04-30Completed
A Double Blind, Randomized, Placebo Controlled, Multi Center Study of OT-101 in Hospitalized COVID-19 Subjects[NCT04801017]Phase 218 participants (Anticipated)Interventional2021-04-30Not yet recruiting
Phase 2 Trial of TGF-β2 Inhibition (OT-101) With Atezolizumab as Second-Line or Third-Line Therapy for Patients Previously Treated With Immunotherapy (+/- Chemotherapy) With Metastatic Non-Small Cell Lung Cancer (NSCLC)[NCT05935774]Phase 20 participants (Actual)Interventional2023-12-01Withdrawn(stopped due to Withdrawn prior to opening to accrual.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00761280 (12) [back to overview]Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Median Time to Progression (Days) by Independent Review for the Intent-to-treat Population (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Tumor Control Rate (CR+PR+SD) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Disease Progression at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Number of Participants
NCT00761280 (12) [back to overview]Disease Progression Rate at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)
NCT00761280 (12) [back to overview]Response Category by Independent Review in the Intent-to-treat Population - Number of Participants
NCT00761280 (12) [back to overview]Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants
NCT00761280 (12) [back to overview]Survival at 24 Months in the Intent-to-treat Population - Number of Participants
NCT00761280 (12) [back to overview]Survival Rate at 12, 18, and 21 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)

Median Duration of Response (Days) by Independent Review (Descriptive Analysis, Only)

"Duration of response was defined as the time from the first documentation of confirmed response (Complete Response, CR, or Partial Response, PR) to the first signs of Progressive Disease (PD), as assessed by the study neuro-oncologist. Median Duration of Response was calculated by Kaplan-Meier estimate.~Censoring rules were:~at the date of randomization -- participants without baseline assessments, or for those with no post-baseline timor assessments who were discontinued for other than progressive disease or death.~at the date of last tumor assessment -- discontinuation other than PD or death, or if a new treatment was started prior to disease progression~at the date of death or last tumor assessment -- death or PD after one missed tumor assessment~at the date of last tumor assessment -- death or PD after more than one missed tumor assessment~at the date of last tumor assessment -- participants on ongoing treatment at data cut-off" (NCT00761280)
Timeframe: Up to 24 months

Interventiondays (Median)
Trabedersen 10 µMNA
ChemotherapyNA

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Median Overall Survival (Days) From Randomization in the Intent-to-treat Population (Descriptive Analysis, Only)

Median overall survival was defined as the date of randomization to the date of death. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. Analysis was by Kaplan-Meier estimation. (NCT00761280)
Timeframe: Up to 24 months

Interventiondays (Median)
Trabedersen 10 µM458.0
Chemotherapy584.5

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Median Time to Progression (Days) by Independent Review for the Intent-to-treat Population (Descriptive Analysis, Only)

Time to progression was calculated from the date of randomization to the date of the first documented tumor progression. Participants who did not progress or died were censored at the last tumor assessment date or the date of start of a new anti-tumor treatment or death. (NCT00761280)
Timeframe: Up to 24 months

Interventiondays (Median)
Trabedersen 10 µM57.0
Chemotherapy153.5

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Overall Response Rate (CR+PR) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)

Overall response rate was the proportion of participants with a best response of Complete Response (CR) or Partial Response (PR) observed from the start of treatment until disease progression. (NCT00761280)
Timeframe: Up to 24 months

Interventionpercentage of participants (Number)
Trabedersen 10 µM14.3
Chemotherapy7.7

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Survival Rate at 24 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)

Survival rate was defined as the proportion of participants known to be alive at 24 months from randomization. If a participant's status was unknown and there was no follow-up information available, they were categorized as 'Died' for the purposes of the analysis. (NCT00761280)
Timeframe: 24 months

Interventionpercentage of participants (Number)
Trabedersen 10 µM28.6
Chemotherapy15.4

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Tumor Control Rate (CR+PR+SD) by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)

Tumor control rate was defined as the proportion of participants assessed as having Complete Response (CR), Partial Response (PR), or Stable Disease (SD). Participants with unknown or missing response were treated as non-responders. (NCT00761280)
Timeframe: Up to 24 months

Interventionpercentage of participants (Number)
Trabedersen 10 µM28.6
Chemotherapy53.8

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Disease Progression at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Number of Participants

"Tumor response was classified based on the (neuro-)radiologist's evaluation:~Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.~Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.~Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.~Stable Disease (SD): all other situations.~Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of Progressed versus Not Progressed. Participants who had MRI assessment results missing or unknown were UNK or missing, and were treated as Progressed for the purposes of the calculation." (NCT00761280)
Timeframe: 10, 12, 14, 16, 18, 21, and 24 months

,
Interventionparticipants (Number)
Progressed at 10 monthsNot progressed at 10 monthsStatus unknown / missing at 10 monthsLost to follow-up at 10 monthsProgressed at 12 monthsNot progressed at 12 monthsStatus unknown / missing at 12 monthsLost to follow-up at 12 monthsProgressed at 14 monthsNot progressed at 14 monthsStatus unknown / missing at 14 monthsLost to follow-up at 14 monthsProgressed at 16 monthsNot progressed at 16 monthsStatus unknown / missing at 16 monthsLost to follow-up at 16 monthsProgressed at 18 monthsNot progressed at 18 monthsStatus unknown / missing at 18 monthsLost to follow-up at 18 monthsProgressed at 21 monthsNot progressed at 21 monthsStatus unknown / missing at 21 monthsLost to follow-up at 21 monthsProgressed at 24 monthsNot progressed at 24 monthsStatus unknown / missing at 24 monthsLost to follow-up at 24 months
Chemotherapy5071507150715071507150715071
Trabedersen 10 µM7340725072507250725071607160

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Disease Progression Rate at 10, 12, 14, 16, 18, 21, and 24 Months by Independent Review in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)

"Tumor response was classified based on the (neuro-)radiologist's evaluation:~Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.~Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.~Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.~Stable Disease (SD): all other situations.~Based on clinical and imaging data, an independent neuro-oncologist made the final assessment of Progressed versus Not Progressed. Participants who had MRI assessment results missing or unknown were UNK or missing, and were treated as Progressed for the purposes of the calculation." (NCT00761280)
Timeframe: 10, 12, 14, 16, 18, 21 and 24 months

,
Interventionpercentage of participants (Number)
Progression rate at 10 monthsProgression rate at 12 monthsProgression rate at 14 monthsProgression rate at 16 monthsProgression rate at 18 monthsProgression rate at 21 monthsProgression rate at 24 months
Chemotherapy100.0100.0100.0100.0100.0100.0100.0
Trabedersen 10 µM78.685.785.785.785.792.992.9

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Response Category by Independent Review in the Intent-to-treat Population - Number of Participants

"Tumor response was classified based on the (neuro-)radiologist's evaluation according to the Macdonald Response Criteria for bidimensionally measurable disease as outlined below:~Complete Response (CR): Disappearance of all enhancing tumor on consecutive MRI scans at least 1 month apart, off steroids, neurologically stable or improved.~Partial Response (PR): ≥50% reduction in size of enhancing tumor on consecutive MRI scans at least 1 month apart, steroids stable or reduced, neurologically stable or improved.~Progressive Disease (PD): ≥25% increase in size of enhancing tumor or any new tumor on MRI scans, steroids stable or increased, neurologically worse.~Stable Disease (SD): all other situations.~Two qualified neuro-radiologists reviewed scans at each MRI time point, with adjudication of discrepancies by a third reviewer. Their findings and clinical information were independently reviewed by a neuro-oncologist, who made the assessment of overall response." (NCT00761280)
Timeframe: Up to 24 months

,
Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)UnknownMissing
Chemotherapy016132
Trabedersen 10 µM022712

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Survival at 12, 18, and 21 Months in the Intent-to-treat Population - Number of Participants

"Survival status was assessed at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category Lost to follow-up for each time-point includes participants who were alive at the last data collection point but did not yet have enough follow-up time to reach the time point." (NCT00761280)
Timeframe: 12, 18, and 21 months

,
Interventionparticipants (Number)
Alive at 12 monthsDied at 12 monthsLost to follow-up at 12 monthsAlive at 18 monthsDied at 18 monthsLost to follow-up at 18 monthsAlive at 21 monthsDied at 21 monthsLost to follow-up at 21 months
Chemotherapy715535355
Trabedersen 10 µM851671572

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Survival at 24 Months in the Intent-to-treat Population - Number of Participants

"Survival status was assessed at 24 months from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. The category Lost to / insufficient follow-up includes participants who were alive at last data collection point but did not yet have enough follow-up time to reach the 24 month time point." (NCT00761280)
Timeframe: 24 months

,
Interventionparticipants (Number)
AliveDiedLost to/insufficient follow-up
Chemotherapy256
Trabedersen 10 µM473

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Survival Rate at 12, 18, and 21 Months in the Intent-to-treat Population - Percentage of Participants (Descriptive Analysis, Only)

Survival rate was defined as the proportion of participants known to be alive at each time-point from randomization. Participants with unknown or missing status were considered treatment failures, i.e., assumed to be dead. (NCT00761280)
Timeframe: 12, 18, and 21 months

,
Interventionpercentage of participants (Number)
Survival rates at 12 monthsSurvival rates at 18 monthsSurvival rates at 21 months
Chemotherapy53.838.523.1
Trabedersen 10 µM57.142.935.7

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SubstanceRelationship StrengthStudiesTrialsClassesRoles
phenol
[no description available]		2.110phenolsantiseptic drug;
disinfectant;
human xenobiotic metabolite;
mouse metabolite
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.		2.0710nucleobase analogue;
organofluorine compound		antimetabolite;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
radiosensitizing agent;
xenobiotic
chloroform
Chloroform: A commonly used laboratory solvent. It was previously used as an anesthetic, but was banned from use in the U.S. due to its suspected carcinogenicity.. chloroform : A one-carbon compound that is methane in which three of the hydrogens are replaced by chlorines.		2.110chloromethanes;
one-carbon compound		carcinogenic agent;
central nervous system drug;
inhalation anaesthetic;
non-polar solvent;
refrigerant
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.		2.0710azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinazolines
deoxycytidine
[no description available]		2.0710pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
capecitabine
Capecitabine: A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.. capecitabine : A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers.		2.0710carbamate ester;
cytidines;
organofluorine compound		antimetabolite;
antineoplastic agent;
prodrug
lapatinib
[no description available]		2.0710furans;
organochlorine compound;
organofluorine compound;
quinazolines		antineoplastic agent;
tyrosine kinase inhibitor
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.		2.07105-formyltetrahydrofolic acidantineoplastic agent;
metabolite
ConditionIndicatedRelationship StrengthStudiesTrials
Benign Neoplasms, Brain
[description not available]		06.0861
Glial Cell Tumors
[description not available]		04.5450
Benign Neoplasms
[description not available]		03.6630
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		06.0861
Glioma
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)		04.5450
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.		03.6630
Astrocytoma, Grade IV
[description not available]		03.4511
Local Neoplasm Recurrence
[description not available]		04.1431
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		03.4511
Angiogenesis, Pathologic
[description not available]		02.0610
Cancer of Pancreas
[description not available]		02.4720
Pancreatic Neoplasms
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).		02.4720