Page last updated: 2024-11-05

plicamycin

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

Description

mithramycin A: structure given in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID133562729
MeSH IDM0013935

Synonyms (1)

Synonym
mithramycin a

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Distamycin A readily inhibited nucleic acid and protein synthesis and was more toxic to the ring stage than to the trophozoite stage in various parasite strains, irrespective of their susceptibility to chloroquine."( Selective toxicity to malaria parasites by non-intercalating DNA-binding ligands.
Ginsburg, H; Krugliak, M; Nissani, E; Williamson, DH, 1993
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (134)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's5 (3.73)18.2507
2000's50 (37.31)29.6817
2010's70 (52.24)24.3611
2020's9 (6.72)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 (0.75%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational1 (0.75%)0.25%
Other132 (98.51%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (3)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Phase I/II Evaluation of Continuous 24h Intravenous Infusion of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Primary Thoracic Malignancies or Carcinomas, Sarcomas or Germ Cell Neoplasms With Pleuropulmonary Metastases [NCT02859415]Phase 1/Phase 23 participants (Actual)Interventional2019-08-08Terminated(stopped due to Slow/Insufficient accrual)
Phase I/II Trial of Mithramycin in Children and Adults With Refractory Extracranial Solid Tumors (Phase I) or Ewing Sarcoma and EWSFLI1 Fusion Transcript (Phase II) [NCT01610570]Phase 1/Phase 28 participants (Actual)Interventional2012-05-10Terminated(stopped due to Study was closed to enrollment before dose level one was completed.)
Phase II Evaluation of Mithramycin, an Inhibitor of Cancer Stem Cell Signaling, in Patients With Malignancies Involving Lungs, Esophagus, Pleura, or Mediastinum [NCT01624090]Phase 216 participants (Actual)Interventional2012-09-06Terminated(stopped due to Study closed due to low accrual.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT01610570 (12) [back to overview]Area Under the Curve Extrapolated to Infinity (AUCinf)
NCT01610570 (12) [back to overview]Area Under the Curve for the Dosing Interval (AUCtau)
NCT01610570 (12) [back to overview]Clearance at Steady State (CLss)
NCT01610570 (12) [back to overview]Half-Life (HL) of Mithramycin
NCT01610570 (12) [back to overview]Maximum Plasma Concentration (Cmax) of Mithramycin Using Non-Compartmental Methods
NCT01610570 (12) [back to overview]Number of Participants With Dose Limiting Toxicity (DLT)
NCT01610570 (12) [back to overview]Number of Participants With Serious and Non-serious Adverse Events
NCT01610570 (12) [back to overview]Volume of Distribution at Steady State (Vss)
NCT01610570 (12) [back to overview]Number of Participants With a Change in Tumor Burden Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)
NCT01610570 (12) [back to overview]Number of Participants With a Change in Tumor Burden Measured by the World Health Organization (WHO) Criteria
NCT01610570 (12) [back to overview]Objective Response Rate (Complete Response (CR) + Partial Response (PR))
NCT01610570 (12) [back to overview]Time to Progression (TTP)
NCT01624090 (1) [back to overview]Number of Participants With Serious and Non-Serious Adverse Events
NCT02859415 (4) [back to overview]Maximum Tolerated Dose (MTD)
NCT02859415 (4) [back to overview]Number of Participants With a Dose-limiting Toxicity (DLT)
NCT02859415 (4) [back to overview]Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
NCT02859415 (4) [back to overview]Number of Participants Whose Best Response is a Complete Response (CR) or Partial Response (PR)

Area Under the Curve Extrapolated to Infinity (AUCinf)

AUC is a measure of the serum concentration of mithramycin over time. It is used to characterize drug absorption. Analysis was performed using the Phoenix 6.3 with WinNonlin noncompartmental method. (NCT01610570)
Timeframe: Prior to dose 1, 3hrs after dose 1 infusion, prior to end of 6hr infusion, 0.25, 0.5, 1,2,3,4,5, & 7hr post infusion, & between 9 & 12hr completion of 1st dose infusion. Trough & end of infusion samples obtained w/day 2,4,&7 doses & 24hr after day 7 dose

Interventionh*ng/mL (Mean)
Phase I Dose Level 1 & Phase II Expansion Phase1544

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Area Under the Curve for the Dosing Interval (AUCtau)

AUCtau is AUC for the dosing interval. Analysis was performed using the Phoenix 6.3 with WinNonlin noncompartmental method. (NCT01610570)
Timeframe: Prior to dose 1, 3hrs after dose 1 infusion, prior to end of 6hr infusion, 0.25, 0.5, 1,2,3,4,5, & 7hr post infusion, & between 9 & 12hr completion of 1st dose infusion. Trough & end of infusion samples obtained w/day 2,4,&7 doses & 24hr after day 7 dose

Interventionh*ng/mL (Mean)
Phase I Dose Level 1 & Phase II Expansion Phase394

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Clearance at Steady State (CLss)

The CL is a quantitative measure of the rate at which a drug substance is removed from the body. Analysis was performed using the Phoenix 6.3 with WinNonlin noncompartmental method. (NCT01610570)
Timeframe: Prior to dose 1, 3hrs after dose 1 infusion, prior to end of 6hr infusion, 0.25, 0.5, 1,2,3,4,5, & 7hr post infusion, & between 9 & 12hr completion of 1st dose infusion. Trough & end of infusion samples obtained w/day 2,4,&7 doses & 24hr after day 7 dose

InterventionL/h (Mean)
Phase I Dose Level 1 & Phase II Expansion Phase1.9

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Half-Life (HL) of Mithramycin

Plasma decay half-life is the time measured for the plasma concentration of the drug to decrease by one half. Analysis was performed using the Phoenix 6.3 with WinNonlin noncompartmental method. (NCT01610570)
Timeframe: Prior to dose 1, 3hrs after dose 1 infusion, prior to end of 6hr infusion, 0.25, 0.5, 1,2,3,4,5, & 7hr post infusion, & between 9 & 12hr completion of 1st dose infusion. Trough & end of infusion samples obtained w/day 2,4,&7 doses & 24hr after day 7 dose

Interventionhours (Mean)
Phase I Dose Level 1 & Phase II Expansion Phase6.8

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Maximum Plasma Concentration (Cmax) of Mithramycin Using Non-Compartmental Methods

The maximum observed analyte concentration in serum was reported. Mithramycin plasma concentrations were measured using high-performance liquid chromatography tandem mass spectroscopic method, and analysis was performed using the Phoenix 6.3 with WinNonlin noncompartmental method. (NCT01610570)
Timeframe: Prior to dose 1, 3hrs after dose 1 infusion, prior to end of 6hr infusion, 0.25, 0.5, 1,2,3,4,5, & 7hr post infusion, & between 9 & 12hr completion of 1st dose infusion. Trough & end of infusion samples obtained w/day 2,4,&7 doses & 24hr after day 7 dose

Interventionng/mL (Mean)
Phase I Dose Level 1 & Phase II Expansion Phase17.8

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Number of Participants With Dose Limiting Toxicity (DLT)

Hematologic DLT was defined as any grade 4 neutropenia (<500/µL) or thrombocytopenia (<25,000/µL) refractory to platelet transfusion, any grade 2 bleeding not promptly (within 6 h of appropriate intervention) corrected with blood product support. Non-hematologic DLT's were any mithramycin-related grade ≥3 toxicity with the exception of grade 3 nausea, vomiting, or diarrhea that was controlled by symptomatic treatment within 72h, asymptomatic grade 3 elevation of serum transaminases that return to ≤grade 1 within 14 days of completing mithramycin administration, and asymptomatic electrolyte abnormalities that are correctable to grade2 or less within 48h. (NCT01610570)
Timeframe: Cycle 1 of therapy (or 28 days)

InterventionParticipants (Count of Participants)
Phase I Dose Level 12
Phase I Dose Level 20
Phase II - Expansion Phase0

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Number of Participants With Serious and Non-serious Adverse Events

Here is the number of participants with serious and non-serious adverse events. For a detailed list of serious and non-serious adverse events see the adverse event module. (NCT01610570)
Timeframe: 95 days

InterventionParticipants (Count of Participants)
Phase I Dose Level 12
Phase II - Expansion Phase6

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Volume of Distribution at Steady State (Vss)

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Analysis was performed using the Phoenix 6.3 with WinNonlin noncompartmental method. (NCT01610570)
Timeframe: Prior to dose 1, 3hrs after dose 1 infusion, prior to end of 6hr infusion, 0.25, 0.5, 1,2,3,4,5, & 7hr post infusion, & between 9 & 12hr completion of 1st dose infusion. Trough & end of infusion samples obtained w/day 2,4,&7 doses & 24hr after day 7 dose

InterventionL (Mean)
Phase I Dose Level 1 & Phase II Expansion Phase293

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Number of Participants With a Change in Tumor Burden Measured by the Response Evaluation Criteria in Solid Tumors (RECIST)

Measurable disease were to be quantified using volumetric magnetic resonance imaging analysis per the RECIST, measuring soft tissue disease. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progressions). Stable disease (SD) is neither shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT01610570)
Timeframe: ≥4 weeks from baseline

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseProgressive DiseaseStable Disease
Phase II - Expansion Phase0060

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Number of Participants With a Change in Tumor Burden Measured by the World Health Organization (WHO) Criteria

Per the WHO criteria, progressive disease is a 25% increase in tumor lesions, or the appearance of any new measureable or non-measureable tumor lesions. Partial response is ≥50% decrease in tumor lesions. Complete response is disappearance of all tumor lesions. Stable disease is 50% decrease in tumor lesions compared to baseline, nor 25% increase compared with nadir. (NCT01610570)
Timeframe: ≥4 weeks from baseline

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseProgressive DiseaseStable Disease
Phase II - Expansion Phase0060

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Objective Response Rate (Complete Response (CR) + Partial Response (PR))

Objective response in children and adolescents with Ewings sarcoma - friend leukemia integration 1 transcription factor to mithramycin is defined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. (NCT01610570)
Timeframe: 1-2 months

Interventionparticipants (Number)
Complete response (CR)Partial response (PR)
Phase II - Expansion Phase00

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Time to Progression (TTP)

TTP is defined as the number of days from enrollment until disease progression, death because of treatment complications, resection of measureable tumor, or last patient follow-up, whichever comes first, assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progressions). Stable disease (SD) is neither shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT01610570)
Timeframe: At date of progression, an average of 56 days

InterventionDays (Number)
Patient #1Patient #2Patient #3Patient #5Patient #7Patient #8
Phase II - Expansion Phase5656126545656

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Number of Participants With Serious and Non-Serious Adverse Events

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01624090)
Timeframe: Date treatment consent signed to date off study, approx. 9 mos & 6 days DL1 30 mcg/kg thoracic group, 2 mos & 16 days DL1 30 mcg/kg extra-thoracic group, 5 mos & 26 days DL-1 25 mcg/kg thoracic group, & 20 days DL-1 25 mcg/kg extra-thoracic group

InterventionParticipants (Count of Participants)
Dose Level 1 - 30 mcg/kg Thoracic Malignancy2
Dose Level 1 - 30 mcg/kg Extra Thoracic Malignancy1
Dose Level -1 - 25 mcg/kg Thoracic Malignancy10
Dose Level -1 - 25 mcg/kg Extra Thoracic Malignancy2

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Maximum Tolerated Dose (MTD)

MTD is defined as the number of participants experiencing a dose-limiting toxicity (DLT). A DLT is defined as Grade 4 or greater anemia or neutropenia exceeding 5 days duration, thrombocytopenia requiring transfusion, or Grade 3 or greater nonhematologic toxicity possibly, probably, or definitely related to the investigational therapy excluding alopecia during Cycle 1 of therapy. (NCT02859415)
Timeframe: At the end of first 14 day cycle at each dose level

Interventionmcg/kg (Number)
All ParticipantsNA

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Number of Participants With a Dose-limiting Toxicity (DLT)

A DLT is defined as Grade 4 or greater anemia or neutropenia exceeding 5 days duration, thrombocytopenia requiring transfusion, or Grade 3 or greater nonhematologic toxicity possibly, probably, or definitely related to the investigational therapy excluding alopecia during Cycle 1 of therapy. (NCT02859415)
Timeframe: Cycle 1

InterventionParticipants (Count of Participants)
Phase I Dose Level 1 Mithramycin 60 mcg/kg0
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg0

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Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT02859415)
Timeframe: Date treatment consent signed to date off study, approximately 1 month and 4 days, and 3 months and 17 days for the first and second group respectively.

InterventionParticipants (Count of Participants)
Phase I Dose Level 1 Mithramycin 60 mcg/kg1
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg2

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Number of Participants Whose Best Response is a Complete Response (CR) or Partial Response (PR)

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (NCT02859415)
Timeframe: every 8 weeks until at disease progression, approximately 3.5 months

InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
Phase I Dose Level -1 Mithramycin 60 mcg/kg Followed by Mithramycin 30 mcg/kg00

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