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Completed

NCT Number: NCT03486314

A Study to Evaluate the Effects of Rifampin on Pharmacokinetics (PK) of Pevonedistat in Participants 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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Emory University, Atlanta, Georgia, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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).

Exclusion criteria

  • 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.

Treatment and study plan

Pevonedistat

Drug

Pevonedistat intravenous infusion.

Other names: MLN4924, TAK-924

Rifampin

Drug

Rifampin capsules.

docetaxel

Drug

Docetaxel intravenous infusion.

carboplatin

Drug

Carboplatin intravenous infusion.

paclitaxel

Drug

Paclitaxel intravenous infusion.

Primary outcomes

  1. 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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.

Sponsors and collaborators

Lead sponsor

Millennium Pharmaceuticals, Inc.

Industry

Registry information

Official study title

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

Important dates

Study start
2018
Primary completion
2019
Study completion
2021
First posted
Apr 3, 2018
Registry last updated
Apr 18, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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