Phase 1
Completed N=8
A Study of [14 C]-Pevonedistat in Participants With Advanced Solid Tumors
Advanced Solid Tumors, Neoplasms, Advanced Solid
Source: ClinicalTrials.gov NCT03057366 ↗
Enrolled (actual)
8
Serious AEs
26.7%
Results posted
May 2019
Primary outcomePrimary: Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat — 234.3; 6862.9 nanogram per milliliter (ng/mL)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat |
234.3; 6862.9 | — |
| PRIMARY Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat |
0.980; 1.000 | — |
| PRIMARY 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 |
1446.9; 59284.0 | — |
| PRIMARY Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material |
293.6; 7336.6 | — |
| PRIMARY Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material |
0.980; 0.980 | — |
| PRIMARY 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 |
3547.3; 133259.0 | — |
| PRIMARY Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval |
19661.05 | — |
| PRIMARY Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval |
25029.45 | — |
| PRIMARY Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body |
44690.50 | — |
| PRIMARY Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose |
1161.47 | — |
| PRIMARY Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose |
2.45 | — |
| PRIMARY Part A: Renal Clearance (CLR) for Pevonedistat |
0.8343 | — |
| SECONDARY Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
4; 5; 2; 1; 2; 1 | — |
| SECONDARY Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces |
49.3; 14.6; 21.5; 4.5; 0.8; 6.5 | — |
| SECONDARY Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment |
0; 0; 0; 0; 2; 0 | — |
Eligibility Criteria
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 [ =) 25% of the hematopoietically active bone marrow.
Data sourced from ClinicalTrials.gov (NCT03057366). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.