A Study to Evaluate the Effects of Pevonedistat on the Corrected QT (QTc) Interval in Participants With Advanced Solid Tumors

June 13, 2022 updated by: Millennium Pharmaceuticals, Inc.

A Randomized, Crossover Phase 1 Study to Evaluate the Effects of Pevonedistat on the QTc Interval in Patients With Advanced Solid Tumors

The purpose of this study is to characterize the effects of 25 and 50 milligram per square meter (mg/m^2) pevonedistat on the Fridericia corrected QT interval (QTcF) of the electrocardiogram (ECG).

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 drug being tested in this study is called pevonedistat. Pevonedistat in combination with standard of care will be used to treat participants who have advanced solid tumors. This study will assess the effects of pevonedistat on the QTc interval in participants with advanced solid tumors.

The study will enroll approximately 45 participants. The study will be conducted in two Parts: Part A and Part B. Part A will have a 2-way crossover design and will involve the collection of triplicate ECGs. In Part A, participants will be randomly assigned to one of the two treatment groups as follow:

  • Pevonedistat 25 mg/m^2 + Pevonedistat 50 mg/m^2
  • Pevonedistat 50 mg/m^2 + Pevonedistat 25 mg/m^2

Eligible participants from Part A will continue treatment in optional Part B with pevonedistat in combination with SoC, docetaxel or carboplatin plus paclitaxel. The investigator will decide which pevonedistat combination 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 9.6 months. Participants will make a final visit to the clinic 30 days after receiving their last dose of study drug for a follow-up assessment.

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.
68

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
    • California
      • Santa Monica, California, United States, 90403
        • Sarcoma Oncology Center
    • Florida
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 23801
        • University of Oklahoma Health Sciences Center
    • Texas
      • Dallas, Texas, United States, 75231
        • Mary Crowley Medical Research
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Participants must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor(s) appropriate for treatment with one of the 2 combination therapies in Part B of this study, 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 longer than 3 months from enrollment in the study.
  4. Recovered (that is, grade less than or equal to [<=] 1 toxicity) from the reversible effects of prior anticancer therapy.
  5. Suitable venous access for the study-required blood sampling (including pharmacokinetic [PK] sampling).

Exclusion Criteria:

  1. Treatment with strong cytochrome P3A (CYP3A) inducers within 14 days before the first dose of pevonedistat. Participants must have no history of amiodarone use within 6 months before the first dose of pevonedistat nor require the use of these medications during the study.
  2. Treatment with QT-prolonging drugs with a risk of causing torsades de pointes (TdP. Participants taking drugs with a possible or conditional risk of QT prolongation or drugs that are to be avoided by participants with congenital long QT syndrome may be considered if on a stable dose, pending discussion and agreement between the investigator and the sponsor.
  3. History of Brugada syndrome, risk factors for TdP, or family history of long QT syndrome.
  4. Implantable cardioverter defibrillator.
  5. Cardiac pacemaker with heart rate (HR) set at a fixed rate and treatment with concomitant medication that may limit increase in HR in response to hypotension (example, high-dose beta blocker).
  6. Known moderate to severe aortic stenosis, moderate to severe mitral stenosis, or other valvulopathy (ongoing).
  7. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

Entry Criteria for Continuation to Optional Part B:

After completing Part A of the study, participants may choose to enter the optional Part B of the study. To be eligible for the optional Part B, participants must have completed Part A and be reassessed to determine if they meet the entry criteria for optional Part B. Only participants who meet the following criteria may enter into Part B:

  • ECOG performance status of 0 to 1.
  • Absolute neutrophil count (ANC) greater than or equal to (>=) 1500 per cubic millimeter (/mm^3).
  • Platelet count >=100,000/mm^3.
  • Laboratory values for hemoglobin, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and serum creatinine or calculated/measured creatinine clearance.
  • Diarrhea symptoms resolved to Grade 1 or better.
  • QTc interval <480 millisecond (msec).
  • Computed tomography (CT) scan or magnetic resonance imaging (MRI) of the chest, abdomen, and pelvis within 28 days of Cycle 1 Day 1.

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: Randomized
  • Interventional Model: Crossover 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 25 mg/m^2 + Pevonedistat 50 mg/m^2
Pevonedistat 25 mg/m^2, infusion, intravenously, once on Day 1 of Cycle 1, followed by pevonedistat 50 mg/m^2, infusion, intravenously, once on Day 8 of Cycle 1.
Drug: Pevonedistat
Pevonedistat intravenous infusion.
Other Names:
  • MLN4924, TAK-924
Experimental: Part A: Pevonedistat 50 mg/m^2 + Pevonedistat 25 mg/m^2
Pevonedistat 50 mg/m^2, infusion, intravenously, once on Day 1 of Cycle 1, followed by pevonedistat 25 mg/m^2, infusion, intravenously, once on Day 8 of Cycle 1.
Drug: Pevonedistat
Pevonedistat intravenous infusion.
Other Names:
  • MLN4924, TAK-924
Experimental: Part B: Pevonedistat
Pevonedistat 25 mg/m^2 in combination with docetaxel 75 mg/m^2 or pevonedistat 20 mg/m^2 in combination with carboplatin plus paclitaxel 175 mg/m^2, infusion, intravenously, once on Day 1 in each 21-day treatment cycle followed by pevonedistat 25 mg/m^2 or 20 mg/m^2 infusion, intravenously, once on Days 3 and 5 in each 21-day treatment cycle for up to 12 cycles or symptomatic deterioration or PD, treatment is discontinued for another reason, or until the study is stopped. The combination and dose of pevonedistat will be based on investigator discretion.
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: Change From Time-matched Baseline in Fridericia-corrected QT Interval (QTcF) After Pevonedistat Administration
Time Frame: Baseline up to Day 8
Change from time-matched baseline in QTcF was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. Data is reported at pre-dose and at multiple timepoints (1, 2, 3, 4, 6, 9, 11 and 24 hours) postdose up to Day 8 in Part A. Analysis of variance (ANOVA) was used for the analysis.
Baseline up to Day 8

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: Change From Time-matched Baseline in Individual Corrected QT Interval (QTcI) After Pevonedistat Administration
Time Frame: Predose, and at multiple time points up to 24 hours post dose on Day 1 or Day 8 in Part A
Change from time-matched baseline in QTcI was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Predose, and at multiple time points up to 24 hours post dose on Day 1 or Day 8 in Part A
Part A: Change From Time-matched Baseline in QRS After Pevonedistat Administration
Time Frame: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Change from time-matched baseline in QRS was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Part A: Change From Time-matched Baseline in PR After Pevonedistat Administration
Time Frame: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Change from time-matched baseline in PR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Part A: Change From Time-matched Baseline in Heart Rate (HR) After Pevonedistat Administration
Time Frame: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Change from time-matched baseline in HR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis.
Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A
Part A: Cmax: Maximum Observed Plasma Concentration for Pevonedistat
Time Frame: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Part A: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for Pevonedistat
Time Frame: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Part A: Terminal Phase Elimination Half-life (t1/2) for Pevonedistat
Time Frame: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A
Part B: Overall Response Rate (ORR)
Time Frame: Up to Cycle 45 (end of treatment) (Cycle length=21 days)
Percentage of participants who achieve an overall response per investigator's assessment at end of treatment,according to Response Evaluation Criteria in Solid Tumor(RECIST),version 1.1 guideline. Complete response(CR):Disappearance of all target lesions.Any pathological lymph nodes(whether target and non target)must have reduction in short axis to <10 millimeter(mm).Partial Response(PR):atleast 30% decrease in sum of diameter of target lesions,taking as reference baseline sum of diameter.Stable Disease(SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression(PD),taking as reference smallest sum of diameter; PD:atleast 20% increase in sum of diameter of target lesions,taking as reference,smallest sum on study(this includes baseline sum if that is smallest on study).In addition to relative increase of 20%,sum must also demonstrate an absolute increase of atleast 5 mm.Appearance of 1 or more new lesions is also considered progression.
Up to Cycle 45 (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.
November 15, 2017

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.
January 7, 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.
June 21, 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).
October 31, 2017

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.
October 31, 2017

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.
November 6, 2017

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.
March 28, 2023

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.
June 13, 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.
June 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-1014
  • 2017-002610-31 (EudraCT Number)
  • U1111-1201-10111 (Registry 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
  • SAP
  • ICF
  • 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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