Clinical trial NCT03486314: A Study to Evaluate the Effects of Rifampin on Pharmacokinetics (PK) of Pevonedistat in Participants With Advanced Solid Tumors
Official title: A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Neoplasm
Keywords: Drug therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-04-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Eligibility 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.

Primary outcomes:
measure: Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
timeFrame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: 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)
timeFrame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: 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)
timeFrame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Secondary outcomes:
measure: Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
timeFrame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
timeFrame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
timeFrame: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
measure: Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
timeFrame: Up to Cycle 17 (end of treatment) (Cycle length =21 days)
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center of Northwestern University
state: Illinois
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Greenville
country: United States
facility: Greenville Health System - Institute for Translational Oncology Research
state: South Carolina
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Zhou X, Vaishampayan U, Mahalingam D, Harvey RD, Chung KY, Sedarati F, Dong C, Faller DV, Venkatakrishnan K, Gupta N. Phase 1 study to evaluate the effects of rifampin on pharmacokinetics of pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors. Invest New Drugs. 2022 Oct;40(5):1042-1050. doi: 10.1007/s10637-022-01286-8. Epub 2022 Aug 6.