NCT03486314

Brief Summary

The purpose of this study is to assess the effect of multiple-dose administration of rifampin on the single dose PK of pevonedistat in adult participants with advanced solid tumors.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2018

Typical duration for phase_1

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 27, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

April 3, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

August 13, 2018

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 10, 2019

Completed
1.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 28, 2021

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

April 18, 2022

Completed
Last Updated

April 18, 2022

Status Verified

February 1, 2022

Enrollment Period

9 months

First QC Date

March 27, 2018

Results QC Date

February 28, 2022

Last Update Submit

February 28, 2022

Conditions

Advanced Solid Neoplasm

Keywords

Drug therapy

Outcome Measures

Primary Outcomes (3)

  • Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

    The Least square (LS) means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.

    Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

  • Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

    The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.

    Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

  • Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

    The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.

    Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Secondary Outcomes (4)

  • Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

    Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

  • Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

    Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

  • Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

    Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

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

    Up to Cycle 17 (end of treatment) (Cycle length =21 days)

Study Arms (2)

Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg

EXPERIMENTAL

Pevonedistat 50 milligram per square meter (mg/m\^2), intravenous infusion, once on Day 1 and 10 along with rifampin 600 milligram (mg), capsule, orally, once daily from Day 3 up to Day 11 in Part A. After completion of Part A, participants had opportunity to continue into optional Part B.

Drug: PevonedistatDrug: Rifampin

Part B: Pevonedistat

EXPERIMENTAL

Pevonedistat 25 mg/m\^2 intravenously in combination with docetaxel 75 mg/m\^2 or at 20 mg/m\^2 in combination with carboplatin +paclitaxel 175 mg/m\^2; pevonedistat was given in combination on Day 1 and as a single agent on Days 3 and 5 of each 21-day cycle. Participants were treated for up to 12 cycles or symptomatic deterioration or PD, treatment was discontinued for another reason, or until the study is stopped in Part B. The choice of combination partner (docetaxel or carboplatin + paclitaxel) was based on investigator discretion. If the sponsor and investigator determine that a participant would derive clinical benefit from continued treatment, the participant may remain on the current combination therapy or receive pevonedistat as a single agent beyond 12 cycles.

Drug: PevonedistatDrug: DocetaxelDrug: CarboplatinDrug: Paclitaxel

Interventions

PevonedistatDRUG

Pevonedistat intravenous infusion.

Also known as: MLN4924, TAK-924
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mgPart B: Pevonedistat
RifampinDRUG

Rifampin capsules.

Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg
DocetaxelDRUG

Docetaxel intravenous infusion.

Part B: Pevonedistat
CarboplatinDRUG

Carboplatin intravenous infusion.

Part B: Pevonedistat
PaclitaxelDRUG

Paclitaxel intravenous infusion.

Part B: Pevonedistat

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Adult participants who have a histologically or cytologically confirmed metastatic or locally advanced solid tumor that is appropriate for treatment with either docetaxel or carboplatin + paclitaxel in Part B of this study, or have progressed despite standard therapy, or for whom conventional therapy is not considered effective.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Expected survival of at least 3 months from the date of enrollment in the study.
  • Recovered (that is, less than or equal to (\<=) Grade 1 toxicity) from the effects of prior antineoplastic therapy.
  • Adequate organ functions (kidney, liver, cardiac, bone marrow).
  • Suitable venous access for the study-required blood sampling (including PK sampling).

You may not qualify if:

  • Prior treatment with radiation therapy involving greater than or equal to (\>=) 25% of the hematopoietically active bone marrow.
  • Life-threatening illness or serious (acute or chronic) medical or psychiatric illness unrelated to cancer.
  • Active, uncontrolled infection or severe infectious disease.
  • Known human immunodeficiency virus (HIV) seropositive or known hepatitis B or hepatitis C infection.
  • With significant heart or pulmonary disease.
  • Requiring chronic treatment with breast cancer resistance protein (BCRP) inhibitors.
  • Criteria for Continuation into Optional Part B:
  • To be eligible for Part B, participants must have completed Part A and be reassessed to determine if they meet the continuation criteria for Part B.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Emory University

Atlanta, Georgia, 30308, United States

Location

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-2013, United States

Location

Greenville Health System - Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

Location

Related Publications (1)

  • Zhou X, Vaishampayan U, Mahalingam D, Harvey RD, Chung KY, Sedarati F, Dong C, Faller DV, Venkatakrishnan K, Gupta N. Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors. Invest New Drugs. 2022 Oct;40(5):1042-1050. doi: 10.1007/s10637-022-01286-8. Epub 2022 Aug 6.

    PMID: 35932388DERIVED

MeSH Terms

Interventions

pevonedistatRifampinDocetaxelCarboplatinPaclitaxel

Intervention Hierarchy (Ancestors)

RifamycinsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsLactams, MacrocyclicMacrocyclic CompoundsPolycyclic CompoundsTaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesCoordination Complexes

Results Point of Contact

Title
Study 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
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
OTHER
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 27, 2018

First Posted

April 3, 2018

Study Start

August 13, 2018

Primary Completion

May 10, 2019

Study Completion

February 28, 2021

Last Updated

April 18, 2022

Results First Posted

April 18, 2022

Record last verified: 2022-02

Data Sharing

IPD Sharing
Will share

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
More information

Locations

US(4)