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

Millennium Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Neoplasm

Treatments: Drug: Pevonedistat; Drug: Paclitaxel; Drug: Rifampin; Drug: Docetaxel; Drug: Carboplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03486314

U1111-1202-2144 (Other Identifier)

Pevonedistat-1015

Details and patient eligibility

About

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.

Full 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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg

Experimental group

Description:

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.

Treatment:

Drug: Rifampin

Drug: Pevonedistat

Part B: Pevonedistat

Experimental group

Description:

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.

Treatment:

Drug: Carboplatin

Drug: Docetaxel

Drug: Pevonedistat

Drug: Paclitaxel