Clinical trial NCT03708211: 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
Official title: A Phase 1, Open-Label Study to Assess the Relative Bioavailability, Effect of Food, and Gastric pH Modification on the Pharmacokinetics of TAK-931 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms, Advanced Solid
Keywords: Drug Therapy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-10-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Part 1, Cmax: Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC
timeFrame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length is equal to [=] 16 days)
measure: Part 1, AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in Reference to PIC
timeFrame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
measure: Part 1, AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-931 Tablets in Reference to PIC
timeFrame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
Secondary outcomes:
measure: Part 1, Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets
timeFrame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
measure: Part 1, CL/F: Oral Clearance for TAK-931
timeFrame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
measure: Part 1, T1/2z: Terminal Disposition Phase Half-life for TAK-931
timeFrame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose (Cycle 0 length = 16 days)
measure: Part 1: Overall Response Rate (ORR)
timeFrame: Baseline up to 8 months
measure: Part 1: Progression-free Survival (PFS)
timeFrame: From the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurred first (up to 8 months)
measure: Part 1: Disease Control Rate (DCR)
timeFrame: Baseline up to 8 months
measure: Part 1: Duration of Response (DOR)
timeFrame: From the date of first documentation of a response to the date of first documentation of PD ( up to 8 months)
measure: Part 1: Percentage of Participants With Serious Adverse Events (SAEs), Treatment-emergent Adverse Events (TEAEs), and TEAEs Leading to Discontinuation or Dose Modification
timeFrame: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)
measure: Part 1: Percentage of Participants With Grade 3 or Higher TEAEs
timeFrame: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)
measure: Part 1: Percentage of Participants With Shift From Baseline Values to Post-baseline Values in Laboratory Parameters
timeFrame: From the start of the study drug up to Day 30 after the last dose of study drug (up to 8 months)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center, Department of Medical Oncology
state: Gelderland
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology
state: Noord-holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center, Department of Clinical Oncology
state: Zuid-holland
city: Rotterdam
country: Netherlands
facility: Erasmus MC Cancer Institute, Department of Internal Oncology
state: Zuid-holland
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: