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

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors, Neoplasms, Advanced Solid

Treatments: Drug: Docetaxel; Drug: Pevonedistat; Drug: Carboplatin; Drug: [14C]-Pevonedistat; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT03057366

2016-004132-37 (EudraCT Number)

U1111-1169-6648 (Registry Identifier)

Pevonedistat-1013

Details and patient eligibility

About

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.

Full 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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

8 participants in 1 patient group

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

Experimental group

Description:

\[14C\]-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.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Docetaxel

Drug: Pevonedistat

Drug: [14C]-Pevonedistat