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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 : Active, not recruiting
First Posted : April 3, 2018
Last Update Posted : May 22, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Tracking Information
First Submitted Date  ICMJE March 27, 2018
First Posted Date  ICMJE April 3, 2018
Last Update Posted Date May 22, 2019
Actual Study Start Date  ICMJE August 13, 2018
Actual Primary Completion Date May 10, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03486314 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 27, 2018)
  • 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 ]
  • 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 ]
  • 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 ]
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Evaluate the Effects of Rifampin on Pharmacokinetics (PK) of Pevonedistat in Participants With Advanced Solid Tumors
Official Title  ICMJE A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors
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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Advanced Solid Neoplasm
Intervention  ICMJE
  • Drug: Pevonedistat
    Pevonedistat intravenous infusion.
    Other Name: MLN4924, TAK-924
  • Drug: Rifampin
    Rifampin capsules.
  • Drug: Docetaxel
    Docetaxel intravenous infusion.
  • Drug: Carboplatin
    Carboplatin intravenous infusion.
  • Drug: Paclitaxel
    Paclitaxel intravenous infusion.
Study Arms  ICMJE
  • Experimental: Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg
    Pevonedistat 50 milligram per square meter (mg/m^2), infusion, intravenously, 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 will have opportunity to continue into optional Part B.
    Interventions:
    • Drug: Pevonedistat
    • Drug: Rifampin
  • Experimental: Part B: Pevonedistat
    Pevonedistat is given intravenously at 25 mg/m^2 in combination with docetaxel 75 mg/m^2 or at 20 mg/m^2 in combination with carboplatin AUC5+paclitaxel 175 mg/m^2; pevonedistat is given in combination on Day 1 and as a single agent on Days 3 and 5 of each 21-day cycle. Participants will be treated for up to 12 cycles or symptomatic deterioration or PD, treatment is discontinued for another reason, or until the study is stopped in Part B. The choice of combination partner (docetaxel or carboplatin + paclitaxel) will be 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.
    Interventions:
    • Drug: Pevonedistat
    • Drug: Docetaxel
    • Drug: Carboplatin
    • Drug: Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 27, 2018)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 9, 2019
Actual Primary Completion Date May 10, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03486314
Other Study ID Numbers  ICMJE Pevonedistat-1015
U1111-1202-2144 ( Other Identifier: WHO )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Responsible Party Takeda ( Millennium Pharmaceuticals, Inc. )
Study Sponsor  ICMJE Millennium Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Millennium Pharmaceuticals, Inc.
PRS Account Takeda
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP