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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03708211
Recruitment Status : Completed
First Posted : October 17, 2018
Last Update Posted : January 18, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

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.

Condition or disease Intervention/treatment Phase
Neoplasms, Advanced Solid Drug: TAK-931 PIC Drug: TAK-931 Tablet Drug: Esomeprazole Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Other
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 Participants With Advanced Solid Tumors
Actual Study Start Date : March 28, 2019
Actual Primary Completion Date : December 3, 2019
Actual Study Completion Date : December 3, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: TAK-931 PIC
TAK-931 PICs.

Drug: TAK-931 Tablet
TAK-931 Tablets.

Experimental: 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.
Drug: TAK-931 PIC
TAK-931 PICs.

Drug: TAK-931 Tablet
TAK-931 Tablets.

Experimental: 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.
Drug: TAK-931 Tablet
TAK-931 Tablets.

Drug: Esomeprazole
Esomeprazole Tablets.

Experimental: 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.
Drug: TAK-931 Tablet
TAK-931 Tablets.

Drug: Esomeprazole
Esomeprazole Tablets.




Primary Outcome Measures :
  1. Part 1: Cmax: Ratio of Geometric Mean of the Maximum Observed Plasma Concentration for TAK-931 Tablets in Reference to PIC [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  2. Part 1: AUClast: Ratio of Geometric Mean of the 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 [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  3. Part 1: AUCinfinity: Ratio of Geometric Mean of the Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-931 Tablets in Reference to PIC [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  4. Part 2: Cmax: Ratio of Geometric Mean of Maximum Observed Plasma Concentration for TAK-931 Tablets in the Presence and Absence of Esomeprazole [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  5. Part 2: AUClast: Ratio of Geometric Mean of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets Under Fed and Fasted Conditions [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  6. Part 2: AUCinfinity: Ratio of Geometric Mean of Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-931 Tablets Under Fed and Fasted Conditions [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  7. Part 2: Cmax: Ratio of Geometric Mean of Maximum Observed Plasma Concentration for TAK-931 Tablets in the Presence and Absence of Esomeprazole [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  8. Part 2: AUClast: Ratio of Geometric Mean of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 Tablets in the Presence and Absence of Esomeprazole [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  9. Part 2: AUCinfinity: Ratio of Geometric Mean of Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-931 Tablets in the Presence and Absence of Esomeprazole [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  10. Part 2: Cmax: Maximum Observed Plasma Concentration of TAK-931 [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  11. Part 2: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  12. Part 2: AUCinfinity: Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-931 [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]

Secondary Outcome Measures :
  1. Part 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 as PIC and Tablets [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  2. Part 1: CL/F: Oral Clearance for TAK-931 as PIC and Tablets [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  3. Part 1: T1/2z: Terminal Disposition Phase Half-Life for TAK-931 as PIC and Tablets [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  4. Part 1: Overall Response Rate (ORR) [ Time Frame: 1 Year ]
    ORR is defined as the sum of percentage of participants with complete response (CR) and partial response (PR). Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), CR is defined as disappearance of all lesions, PR is defined as at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of lesions, taking as reference the baseline sum LD.

  5. Part 1: Progression-free Survival (PFS) [ Time Frame: From the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurs first (1 year) ]
    PFS is defined as the time from the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurs first. Per RECIST V1.1, Progressive disease (PD) is defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  6. Part 1: Disease Control Rate (DCR) [ Time Frame: 1 Year ]
    DCR is defined as percentage of participants with CR, PR plus stable disease (SD) greater than or equal to (>=) 1 post baseline computed tomography (CT) scan evaluation from treatment initiation to qualify for DCR. Per RECIST v 1.1, CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD is defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  7. Part 1: Duration of Response (DOR) [ Time Frame: From the date of first documentation of a response to the date of first documentation of PD (1 year) ]
    DOR is defined as the time from the date of first documentation of a response to the date of first documentation of PD. Per RECIST v1.1, CR is defined as disappearance of all lesions, PR is defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD is defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  8. Part 1: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation or Dose Modification [ Time Frame: 1 Year ]
  9. Part 1: Percentage of Participants with Grade >= 3 TEAEs [ Time Frame: 1 Year ]
    TEAEs Grades will be evaluated as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life threatening; Grade 4 scaled as life-threatening consequences.

  10. Part 1: Percentage of Participants with Clinically Abnormal Laboratory Values [ Time Frame: 1 Year ]
  11. Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 Tablets Under Fasted and Fed Conditions [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  12. Part 2: (CL/F): Oral Clearance for TAK-931 Tablets Under Fasted and Fed Conditions [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  13. Part 2: T1/2z: Terminal Disposition Phase Half-Life for TAK-931 Tablets Under Fasted and Fed Conditions [ Time Frame: Cycle 0 Days 1 and 3 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  14. Part 2: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-931 Tablets in Absence and Presence of Esomeprazole [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  15. Part 2: CL/F: Oral Clearance for TAK-931 Tablets in Absence and Presence of Esomeprazole [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  16. Part 2: T1/2z: Terminal Disposition Phase Half-Life for TAK-931 Tablets in Absence and Presence of Esomeprazole [ Time Frame: Cycle 0 Days 1, 3 and 12 pre-dose and at multiple time points (up to 48 hours) post-dose ]
  17. Part 2: ORR [ Time Frame: 1 Year ]
    ORR is defined as the sum of percentage of participants with CR and PR. Per RECIST v1.1, CR is defined as disappearance of all lesions, PR is defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD.

  18. Part 2: PFS [ Time Frame: From the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurs first (1 year) ]
    PFS is defined as the time from the date of randomization to the date of first documentation of PD or death due to any cause, whichever occurs first. Per RECIST V1.1, PD is defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  19. Part 2: DCR [ Time Frame: 1 Year ]
    DCR is defined as percentage of participants with CR, PR plus SD >=1 post baseline CT scan evaluation from treatment initiation to qualify for DCR. Per RECIST v 1.1, CR is defined as disappearance of all lesions. PR is defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD is defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

  20. Part 2: DOR [ Time Frame: From the date of first documentation of a response to the date of first documentation of PD (1 year) ]
    DOR is defined as the time from the date of first documentation of a response to the date of first documentation of PD. Per RECIST v1.1, CR is defined as disappearance of all lesions, PR is defined as at least a 30% decrease in the sum of the LD of lesions, taking as reference the baseline sum LD. PD is defined as at least a 20% increase in the sum of the LD of lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  21. Part 2: Percentage of Participants With TEAEs, SAEs, and TEAEs Leading to Discontinuation or Dose Modification [ Time Frame: 1 Year ]
  22. Part 2: Percentage of Participants with Grade >= 3 TEAEs [ Time Frame: 1 Year ]
    TEAEs Grades will be evaluated as per NCI CTCAE, version 5.0. Grade 1 scaled as Mild; Grade 2 scaled as Moderate; Grade 3 scaled as severe or medically significant but not immediately life threatening; Grade 4 scaled as life-threatening consequences.

  23. Part 2: Percentage of Participants with Clinically Abnormal Laboratory Values [ Time Frame: 1 Year ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 pharmacokinetic (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03708211


Locations
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Netherlands
Radboud University Medical Center, Department of Medical Oncology
Nijmegen, Gelderland, Netherlands, 6525 GA
Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Medical Oncology
Amsterdam, Noord-holland, Netherlands, 1066 CX
Leiden University Medical Center, Department of Clinical Oncology
Leiden, Zuid-holland, Netherlands, 2333 ZA
Erasmus MC Cancer Institute, Department of Internal Oncology
Rotterdam, Zuid-holland, Netherlands, 3015 GD
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Millennium Pharmaceuticals, Inc.

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03708211    
Other Study ID Numbers: TAK-931-1003
2017-004629-34 ( EudraCT Number )
U1111-1214-4266 ( Registry Identifier: WHO )
NL66709.091.18 ( Registry Identifier: Netherlands (CCMO) )
First Posted: October 17, 2018    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug therapy
Additional relevant MeSH terms:
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Esomeprazole
Anti-Ulcer Agents
Gastrointestinal Agents
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action