A Study to Evaluate the Effects of Rifampin on Pharmacokinetics (PK) of Pevonedistat in Participants With Advanced Solid Tumors

February 28, 2022 updated by: Millennium Pharmaceuticals, Inc.

A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The study will enroll approximately 20 participants. The study will be conducted in two Parts: Part A and optional Part B. Part A will have a drug-drug interaction (DDI) assessment. In Part A, participants will be assigned to:

• Pevonedistat 50 mg/m^2 + Rifampin

Eligible participants from Part A will continue treatment in optional Part B with pevonedistat in combination with SoC chemotherapy, docetaxel or carboplatin plus paclitaxel. The investigator will decide which SoC combination partner a participant will receive.

  • Pevonedistat 25 mg/m^2 + Docetaxel
  • Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 18 months. Participants will make a final visit to the clinic 30 days after receiving their last dose of study drug or before the start of subsequent therapy.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory University
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
    • Michigan
      • Detroit, Michigan, United States, 48201-2013
        • Barbara Ann Karmanos Cancer Institute
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Health System - Institute for Translational Oncology Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. 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.
  2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  3. Expected survival of at least 3 months from the date of enrollment in the study.
  4. Recovered (that is, less than or equal to (<=) Grade 1 toxicity) from the effects of prior antineoplastic therapy.
  5. Adequate organ functions (kidney, liver, cardiac, bone marrow).
  6. Suitable venous access for the study-required blood sampling (including PK sampling).

Exclusion Criteria:

  1. Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of the hematopoietically active bone marrow.
  2. Life-threatening illness or serious (acute or chronic) medical or psychiatric illness unrelated to cancer.
  3. Active, uncontrolled infection or severe infectious disease.
  4. Known human immunodeficiency virus (HIV) seropositive or known hepatitis B or hepatitis C infection.
  5. With significant heart or pulmonary disease.
  6. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg
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: Pevonedistat
Pevonedistat intravenous infusion.
Other Names:
  • MLN4924, TAK-924
Drug: Rifampin
Rifampin capsules.
Experimental: Part B: Pevonedistat
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: Pevonedistat
Pevonedistat intravenous infusion.
Other Names:
  • MLN4924, TAK-924
Drug: Docetaxel
Docetaxel intravenous infusion.
Drug: Carboplatin
Carboplatin intravenous infusion.
Drug: Paclitaxel
Paclitaxel intravenous infusion.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
Time Frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
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)
Time Frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
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)
Time Frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
Time Frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
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)
Time Frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
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)
Time Frame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
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
Time Frame: Up to Cycle 17 (end of treatment) (Cycle length =21 days)
Best overall response was defined as participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target and non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least 30 percent (%) decrease in sum of diameter of target lesions, taking as reference baseline sum of diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum of diameter. PD: at least 20% increase in sum of diameter of target lesions, taking as reference, smallest sum on study.
Up to Cycle 17 (end of treatment) (Cycle length =21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Millennium Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 13, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 10, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 27, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 3, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 18, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Pevonedistat-1015
  • U1111-1202-2144 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

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.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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