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

NCT03057366 | Completed Phase 1 Results DMC FDA Drug

• 3 other identifiers: Pevonedistat-1013U1111-1169-66482016-004132-37
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Advanced Solid Tumors, Neoplasms, Advanced Solid

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (12)

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

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

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

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

• 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

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

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

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

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

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

• 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

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

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

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

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

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

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

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

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

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

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

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

• Part A: Renal Clearance (CLR) for Pevonedistat

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

Secondary Outcomes (3)

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

  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)

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

  Up to 168 hours post-dose

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

  Up to Cycle 11 (Cycle length =21 days)

Study Arms (1)

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

EXPERIMENTAL

\[14C\]-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.

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

Interventions

Pevonedistat DRUG

Pevonedistat intravenous infusion.

Also known as: MLN4924; TAK-924

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

[14C]-Pevonedistat DRUG

\[14C\]-Pevonedistat intravenous infusion.

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

Docetaxel DRUG

Docetaxel intravenous infusion.

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

Carboplatin DRUG

Carboplatin intravenous infusion.

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

Paclitaxel DRUG

Paclitaxel intravenous infusion.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead

Study Sites (2)

Magyar Honvédség Egészségügyi Központ Onkológiai osztály

Budapest, 1062, Hungary

Location

PRA Magyarország Kft. Fázis I-es Klinikai Farmakológiai Vizsgálóhely

Budapest, 1076, Hungary

Location

Related Publications (1)

• 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.

  PMID: 33089874 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

pevonedistat; Docetaxel; Carboplatin; Paclitaxel

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Results Point of Contact

• Title: Medical Director
• Organization: Takeda

trialdisclosures@takeda.com

+1-877-825-3327

Study Officials

• Medical Director

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2017
• First Posted: February 20, 2017
• Study Start: May 11, 2017
• Primary Completion: February 8, 2018
• Study Completion: November 5, 2018
• Last Updated: November 18, 2019
• Results First Posted: May 8, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share

Locations

HU (2)