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Completed

NCT Number: NCT03057366

A Study of [14 C]-Pevonedistat in Participants With Advanced Solid Tumors

The purpose of this study is to assess the mass balance (that is, cumulative excretion of total radioactivity [TRA] in urine and feces) and to characterize the pharmacokinetics (PK) of pevonedistat in whole blood, plasma, and urine, and of TRA in plasma and whole blood following a single 1-hour infusion of 25 milligram per square meter (mg/m^2) [14C]-pevonedistat intravenous (IV) solution containing approximately 60 to 85 microcurie (mCi) (approximately 2.22-3.145 megabecquerel [MBq]) of TRA in participants with advanced solid tumors in Part A.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Magyar Honvédség Egészségügyi Központ Onkológiai osztály, Budapest, Hungary

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About this study

The drug being tested in this study is called Pevonedistat. Pevonedistat is being tested to treat people with advanced solid tumors.

The study will enroll approximately 4 to 6 pharmacokinetics (PK)-evaluable participants in part A. After completion of the mass balance and absorption, distribution, metabolism, excretion (ADME) assessment in Part A of the study, eligible participants will have the opportunity to continue into Part B at a secondary study site, which would begin in approximately 2 weeks of completion of Part A.

  • [14C]-Pevonedistat 25 mg/m^2
  • Part B (optional): Pevonedistat in combination with chemotherapy regimens (Pevonedistat 25 mg/m^2 + docetaxel 75 mg/m^2 or pevonedistat 20 mg/m^2 + carboplatin 20 mg/m^2 + paclitaxel 175 mg/m^2)

All participants will receive study drug via intravenous route. This multi-center trial will be conducted in Hungary. Participants will remain confined to the study site for 9 to 14 days in Part A. Participation in Part B is optional, participants will be re-evaluated for inclusion/exclusion criteria before administrating treatment. Participants will undergo treatment in Part B for a maximum of 12 cycles (21 days cycle each) and will include approximately 36 weeks for Part A and B combined. Participants will attend an end of study visit 30 days after the last dose of study drug in both Part A and B.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Have a histologically or cytologically confirmed metastatic or locally advanced and incurable solid tumor that is felt to be appropriate for treatment with one of the 2 chemotherapy regimens in Part B of this study (carboplatin+paclitaxel or docetaxel), or have progressed despite prior standard therapy, or for whom conventional therapy is not considered effective. The tumor must be radiographically or clinically evaluable and/or measurable.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Expected survival longer than 3 months from enrollment in the study.
  • Recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the effects of prior antineoplastic therapy.

Exclusion criteria

  • Has irregular defecation patterns (less than 1 defecation per 2 days or excessive diarrhea) and/or has a history of changes in bowel habits with daily routine or environment changes.
  • Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.

Treatment and study plan

Pevonedistat

Drug

Pevonedistat intravenous infusion.

Other names: MLN4924; TAK-924

[14C]-Pevonedistat

Drug

[14C]-Pevonedistat intravenous infusion.

docetaxel

Drug

Docetaxel intravenous infusion.

carboplatin

Drug

Carboplatin intravenous infusion.

paclitaxel

Drug

Paclitaxel intravenous infusion.

Primary outcomes

  1. Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  2. Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  3. Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  4. Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  5. Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  6. Part A: AUClast: Area Under the Plasma and Whole Blood TRA Concentration Curve From Time 0 to Time of the Last Quantifiable Concentration for [14C]-Pevonedistat Drug-related Material

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  7. Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  8. Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  9. Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  10. Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  11. Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

  12. Part A: Renal Clearance (CLR) for Pevonedistat

    Time frame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Secondary outcomes

  1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

    Time frame: Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days)

  2. Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces

    Time frame: Up to 168 hours post-dose

  3. Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment

    Time frame: Up to Cycle 11 (Cycle length =21 days)

    The best overall response was defined as the participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Pevonedistat in Patients With Advanced Solid Tumors

Important dates

Study start
2017
Primary completion
2018
Study completion
2018
First posted
Feb 20, 2017
Registry last updated
Nov 18, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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