Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03486314
Recruitment Status : Completed
First Posted : April 3, 2018
Last Update Posted : March 9, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Neoplasm Drug: Pevonedistat Drug: Rifampin Drug: Docetaxel Drug: Carboplatin Drug: Paclitaxel Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors
Actual Study Start Date : August 13, 2018
Actual Primary Completion Date : May 10, 2019
Actual Study Completion Date : February 28, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Rifampin

Arm Intervention/treatment
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 Name: 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 Name: MLN4924, TAK-924

Drug: Docetaxel
Docetaxel intravenous infusion.

Drug: Carboplatin
Carboplatin intravenous infusion.

Drug: Paclitaxel
Paclitaxel intravenous infusion.




Primary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for Pevonedistat without Rifampin [ Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  2. Cmax: Maximum Observed Plasma Concentration for Pevonedistat with Rifampin [ Time Frame: Day 10 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  3. Part A: AUClast: Area under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Pevonedistat without Rifampin [ Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  4. Part A: AUClast: Area under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Quantifiable Concentration for Pevonedistat with Rifampin [ Time Frame: Day 10 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  5. Part A: AUC∞: Area under the Plasma Concentration-time Curve from Time 0 to Infinity for Pevonedistat without Rifampin [ Time Frame: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  6. Part A: AUC∞: Area under the Plasma Concentration-time Curve from Time 0 to Infinity for Pevonedistat with Rifampin [ Time Frame: Day 10 pre-dose and at multiple time points (up to 48 hours) post-dose ]

Secondary Outcome Measures :
  1. Part A: Total Clearance after Intravenous Administration (CL) for Pevonedistat with Rifampin (Day 1) and without 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 with Rifampin (Day 1) and without 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 with Rifampin (Day 1) and without 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: Overall Response Rate (ORR) [ Time Frame: Baseline up to 12 months ]
    Percentage of participants who achieve an overall response per investigator's assessment at end of treatment, according to response evaluation criteria in solid tumors (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 less than (<) 10 millimeter (mm).Partial Response (PR): at least 30 percent (%) 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: at least 20% increase in sum of diameter of target lesions, taking as reference, smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. Appearance of 1 or more new lesions is also considered progression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03486314


Locations
Layout table for location information
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30308
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center of Northwestern University
Chicago, Illinois, United States, 60611
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-2013
United States, South Carolina
Greenville Health System - Institute for Translational Oncology Research
Greenville, South Carolina, United States, 29605
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Layout table for investigator information
Study Director: Medical Director Millennium Pharmaceuticals, Inc.
Layout table for additonal information
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03486314    
Other Study ID Numbers: Pevonedistat-1015
U1111-1202-2144 ( Other Identifier: WHO )
First Posted: April 3, 2018    Key Record Dates
Last Update Posted: March 9, 2021
Last Verified: March 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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.
URL: https://vivli.org/ourmember/takeda/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug therapy
Additional relevant MeSH terms:
Layout table for MeSH terms
Rifampin
Paclitaxel
Docetaxel
Carboplatin
Pevonedistat
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents
Leprostatic Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP2C8 Inducers
Cytochrome P-450 CYP2C19 Inducers
Cytochrome P-450 CYP2C9 Inducers
Cytochrome P-450 CYP3A Inducers