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

NCT ID: NCT03057366

Last Updated: 2019-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-11
• Study Completion Date: 2018-11-05

Brief Summary

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.

Detailed Description

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.

Conditions

Advanced Solid Tumors, Neoplasms, Advanced Solid

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

[14C]-Pevonedistat 25 mg/m^2

\[14C\]-pevonedistat (containing approximately 60-98 mCi \[approximately 2.22-3.626 MBq\] of radioactive tracer), infusion, intravenously, single dose on Day 1 of Week 1 in Part A. After completion of Part A, participants will have opportunity to continue into Part B. Participant will receive Pevonedistat 25 mg/m\^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles along with docetaxel 75 mg/m\^2, infusion, intravenously, over 1 hour on Day 1 of each 21 day cycle; or pevonedistat 20 mg/m\^2, infusion, intravenously, single dose on Days 1, 3 and 5 of each 21 day cycle, for up to 12 cycles, followed by paclitaxel 175 mg/m\^2, infusion, intravenously, over 3 hours along with carboplatin 20 mg/m\^2, infusion, intravenously, over 30 minutes on Day 1 of 21 each cycle up to 12 cycles. Based on investigator and sponsor discretion, participants deriving benefits will continue to receive current combination therapy or pevonedistat alone beyond 12 cycles.

Group Type: EXPERIMENTAL

Pevonedistat

Intervention Type: DRUG

Pevonedistat intravenous infusion.

[14C]-Pevonedistat

Intervention Type: DRUG

\[14C\]-Pevonedistat intravenous infusion.

Docetaxel

Intervention Type: DRUG

Docetaxel intravenous infusion.

Carboplatin

Intervention Type: DRUG

Carboplatin intravenous infusion.

Paclitaxel

Intervention Type: DRUG

Paclitaxel intravenous infusion.

Interventions

Pevonedistat

Pevonedistat intravenous infusion.

Intervention Type: DRUG

[14C]-Pevonedistat

\[14C\]-Pevonedistat intravenous infusion.

Intervention Type: DRUG

Docetaxel

Docetaxel intravenous infusion.

Intervention Type: DRUG

Carboplatin

Carboplatin intravenous infusion.

Intervention Type: DRUG

Paclitaxel

Paclitaxel intravenous infusion.

Intervention Type: DRUG

Other Intervention Names

MLN4924; TAK-924

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

3. Expected survival longer than 3 months from enrollment in the study.

4. Recovered (that is, less than or equal to [<=] Grade 1 toxicity) from the effects of prior antineoplastic therapy.

Exclusion Criteria

1. 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.

2. Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Magyar Honvédség Egészségügyi Központ Onkológiai osztály

Budapest, , Hungary

PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely

Budapest, , Hungary

Countries

Hungary

References

Zhou X, Sedarati F, Faller DV, Zhao D, Faessel HM, Chowdhury S, Bolleddula J, Li Y, Venkatakrishnan K, Papai Z. Phase I study assessing the mass balance, pharmacokinetics, and excretion of [14C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors. Invest New Drugs. 2021 Apr;39(2):488-498. doi: 10.1007/s10637-020-01017-x. Epub 2020 Oct 22.

Reference Type: DERIVED

PMID: 33089874 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1169-6648

Identifier Type: REGISTRY

Identifier Source: secondary_id

2016-004132-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Pevonedistat-1013

Identifier Type: -

Identifier Source: org_study_id