Clinical trial NCT03057366: A Study of [14 C]-Pevonedistat in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Pevonedistat in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors, Neoplasms, Advanced Solid
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2017-02-20
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: 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
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: 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
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
measure: Part A: Renal Clearance (CLR) for Pevonedistat
timeFrame: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
Secondary outcomes:
measure: Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: 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)
measure: Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces
timeFrame: Up to 168 hours post-dose
measure: Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
timeFrame: Up to Cycle 11 (Cycle length =21 days)
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Magyar Honvédség Egészségügyi Központ Onkológiai osztály
city: Budapest
country: Hungary
facility: PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.