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

Advanced Solid Neoplasm Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03486314
• Other study ID #: Pevonedistat-1015
• Secondary ID: U1111-1202-2144
• Status: Completed
• Phase: Phase 1
• Start date: August 13, 2018
• Est. completion date: February 28, 2021

Study information

• Verified date: February 2022
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 28, 2021
• Est. primary completion date: May 10, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Neoplasm

Intervention

Drug:
• Pevonedistat
Pevonedistat intravenous infusion.
• Rifampin
Rifampin capsules.
• Docetaxel
Docetaxel intravenous infusion.
• Carboplatin
Carboplatin intravenous infusion.
• Paclitaxel
Paclitaxel intravenous infusion.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	Robert H. Lurie Comprehensive Cancer Center of Northwestern University	Chicago	Illinois
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Greenville Health System - Institute for Translational Oncology Research	Greenville	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Millennium Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)	The Least square (LS) means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.	Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Primary	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)	The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.	Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Primary	Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC8) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)	The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model.	Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Secondary	Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)		Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Secondary	Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)		Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Secondary	Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)		Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose
Secondary	Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment	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.	Up to Cycle 17 (end of treatment) (Cycle length =21 days)