A Study to Assess the Relative Bioavailability, Effect of Food, and Gastric Potential Hydrogen (pH) Modification on the Pharmacokinetics (PK) of TAK-931 in Participants With Advanced Solid Tumors

NCT ID: NCT03708211

Last Updated: 2020-12-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-28
• Study Completion Date: 2019-12-03

Brief Summary

The purpose of this study is to estimate the relative bioavailability of TAK-931 tablets in reference to powder-in capsule (PIC) and to assess the effect of food and esomeprazole on the pharmacokinetics (PK) of TAK-931 as a tablet.

Detailed Description

The drug being tested in this study is called TAK-931. TAK 931 is being tested to treat participants who have advanced solid tumors. This study will look at relative bioavailability, effect of food and gastric pH modification on the PK of TAK-931.

The study will enroll approximately 44 participants. The study will be conducted in 2 parts: Part 1 and Part 2. In Part 1 and Part 2, participants will be randomly assigned (by chance, like flipping a coin) in a crossover design. In Part 1, participants will be assigned to 1 of the 2 following treatment sequences:

• TAK-931 80 mg PIC + TAK-931 80 mg Tablet
• TAK-931 80 mg Tablet + TAK-931 80 mg PIC

Part 2 of the study will be initiated, once the preliminary PK data from Part 1 is available to determine the relative bioavailability of the tablet formulation in reference to PIC and to calculate the single dose of TAK-931 tablet to be used in Part 2.In Part 2, participants will be assigned to 1 of the 2 following treatment sequences:

• TAK-931 TBD Fed + TAK-931 TBD Fasted
• TAK-931 TBD Fasted + TAK-931 TBD Fed

This multi-center trial will be conducted in the Netherlands. The overall time to participate in this study is approximately 2 years. Participants will make multiple visits to the clinic and will be contacted for approximately 30 days after receiving their last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first for a follow up assessment.

Conditions

Neoplasms, Advanced Solid

Keywords

Drug Therapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Part1: TAK-931 80 mg PIC + TAK-931 80 mg Tablet

TAK-931 80 milligram (mg), PIC, orally, once on Day 1 Cycle 0 (16-day treatment cycle), followed by TAK-931 80 mg, tablet, orally, once on Day 3 Cycle 0, further followed by TAK-931 50 mg, PIC, orally, once daily from Day 5 to Day 16 Cycle 0. Participants will receive TAK-931 50 mg PIC, orally, once daily for up to 14 days in 21-day treatment cycles until progressive disease (PD), or unacceptable toxicity or any treatment discontinuation is determined.

Group Type: EXPERIMENTAL

TAK-931 PIC

Intervention Type: DRUG

TAK-931 PICs.

TAK-931 Tablet

Intervention Type: DRUG

TAK-931 Tablets.

Part1: TAK-931 80 mg Tablet + TAK-931 80 mg PIC

TAK-931 80 mg, tablet, orally, once on Day 1 of Cycle 0 (16-day treatment cycle), followed by TAK-931 80 mg, PIC, orally, once on Day 3 Cycle 0, further followed by TAK-931 50 mg, PIC, orally, once daily from Day 5 to Day 16 Cycle 0. Participants will receive TAK-931 50 mg PIC, orally, once daily for up to 14 days in 21-day treatment cycles until PD, or unacceptable toxicity or any treatment discontinuation is determined.

Group Type: EXPERIMENTAL

TAK-931 PIC

Intervention Type: DRUG

TAK-931 PICs.

TAK-931 Tablet

Intervention Type: DRUG

TAK-931 Tablets.

Part 2: TAK-931 Fed + TAK-931 Fasted + Esomeprazole 40 mg

TAK-931 tablet, orally, once under fed state on Day 1 Cycle 0 (22-day treatment cycle), followed by TAK-931 tablet, orally, once under fasted state on Day 3 Cycle 0, further followed by esomeprazole 40 mg, tablet, orally, once daily from Day 5 to Day 13 Cycle 0 and TAK-931 tablet, orally, once on Day 12, Day 14 to Day 22. Participants will receive TAK-931 tablets, orally, once daily for up to 14 days in 21-day treatment cycles until PD, unacceptable toxicity or any treatment discontinuation is determined. Dose of TAK-931 in Part 2 will be determined based on relative bioavailability data available from Part 1 of the study.

Group Type: EXPERIMENTAL

TAK-931 Tablet

Intervention Type: DRUG

TAK-931 Tablets.

Esomeprazole

Intervention Type: DRUG

Esomeprazole Tablets.

Part 2: TAK-931 Fasted + TAK-931 Fed + Esomeprazole 40 mg

TAK-931 tablet, orally, once under fasted state on Day 1 Cycle 0 (22-day treatment cycle), followed by TAK-931 tablet, orally, once under fed state on Day 3 Cycle 0, further followed by esomeprazole 40 mg, tablet, orally, once daily from Day 5 to Day 13 Cycle 0 and TAK-931 tablet, orally, once on Day 12, Day 14 to Day 22. Participants will receive TAK-931 tablets, orally, once daily for up to 14 days in 21-day treatment cycles until PD, unacceptable toxicity or any treatment discontinuation is determined. Dose of TAK-931 in Part 2 will be determined based on relative bioavailability data available from Part 1 of the study.

Group Type: EXPERIMENTAL

TAK-931 Tablet

Intervention Type: DRUG

TAK-931 Tablets.

Esomeprazole

Intervention Type: DRUG

Esomeprazole Tablets.

Interventions

TAK-931 PIC

TAK-931 PICs.

Intervention Type: DRUG

TAK-931 Tablet

TAK-931 Tablets.

Intervention Type: DRUG

Esomeprazole

Esomeprazole Tablets.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult participants with histologically or cytologically confirmed metastatic or locally advanced or metastatic solid tumors for whom there is no available standard treatment with proven survival benefit, this therapy is not indicated, or it is refused by the participant. Based on the nonclinical data, the following indications may have a higher probability of clinical benefit: high-grade serous ovarian cancer, uterine carcinosarcoma, squamous esophageal cancer, squamous non-small cell lung carcinoma (NSCLC), rectal adenocarcinoma, and in general tumors with known tumor protein 53 (TP53) gene mutations. For any of these preferred indications, participants should have exhausted standard therapeutic options with a proven survival benefit.

2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

3. Recovered to Grade 1 or baseline from all toxic effects of previous therapy (except alopecia or neuropathy).

4. Suitable venous access for the study-required blood sampling including PK and pharmacodynamic sampling.

5. Must have a radiographically or clinically evaluable tumor, but measurable disease as defined by RECIST v1.1 is not required for participation in this study.

Exclusion Criteria

1. Participants who require continuous use of proton pump inhibitors (PPIs) or histamine-2 (H2) receptor antagonists and participants who are taking PPIs within 5 days before the first dose of study drug.

2. Treatment with clinically significant enzyme inducers, such as phenytoin, carbamazepine, enzalutamide, mitotane, ritonavir, rifampin, or St John's wort within 14 days before the first dose of study drug.

3. With treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or CT) during the screening period.

4. Part 2 only: known hypersensitivity to PPIs (example, angioedema or anaphylaxis have occurred).

5. Part 2 only: not being able or willing to take one high fat breakfast as indicated in the protocol.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Radboud University Medical Center, Department of Medical Oncology

Nijmegen, Gelderland, Netherlands

Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology

Amsterdam, North Holland, Netherlands

Leiden University Medical Center, Department of Clinical Oncology

Leiden, South Holland, Netherlands

Erasmus MC Cancer Institute, Department of Internal Oncology

Rotterdam, South Holland, Netherlands

Countries

Netherlands

References

Steeghs N, Pruis M, van Herpen C, Lu V, Redman J, Zhou X. A phase 1 open-label study to assess the relative bioavailability of TAK-931 tablets in reference to powder-in-capsule in patients with advanced solid tumors. Invest New Drugs. 2023 Feb;41(1):53-59. doi: 10.1007/s10637-022-01318-3. Epub 2022 Nov 21.

Reference Type: DERIVED

PMID: 36409435 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-004629-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1214-4266

Identifier Type: REGISTRY

Identifier Source: secondary_id

NL66709.091.18

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-931-1003

Identifier Type: -

Identifier Source: org_study_id