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A Study to Evaluate TAK-931 in Participants With Advanced Nonhematologic 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. Identifier: NCT02699749
Recruitment Status : Completed
First Posted : March 4, 2016
Last Update Posted : January 18, 2020
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and maximum tolerated dose (MTD) of TAK-931 in participants with advanced nonhematologic tumors.

Condition or disease Intervention/treatment Phase
Nonhematologic Neoplasms, Advanced Drug: TAK-931 Phase 1

Detailed Description:

The drug being under investigation in this study is called TAK-931. The effect of TAK-931 is being evaluated in up to 100 participants who have nonhematologic (solid) neoplasms. This study will look at the safety, tolerability, and PK to determine the maximum tolerated dose (MTD) of TAK-931.

This multi-center trial will be conducted in Japan. The overall study duration is approximately 42 months for total of dose escalation cohorts and the safety expansion cohort. Participants will make multiple visits to the clinic with final visit approximately 30-40 days after last dose of study drug for a follow-up assessment.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: An Open-Label, Phase 1, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 (CDC7) Inhibitor, in Adult Patients With Advanced Nonhematologic Tumors
Actual Study Start Date : March 24, 2016
Actual Primary Completion Date : December 21, 2019
Actual Study Completion Date : December 21, 2019

Arm Intervention/treatment
Experimental: TAK-931

TAK-931 30 mg, capsules, orally, QD or BID on Days 1-14 of each 21-day treatment cycle in dosing schedule A followed by dosing schedule B, C, D, E and F. In dosing schedules B through F, starting doses and dosing escalations will vary depending on the dosing data obtained from dosing in the previous schedule.

Dose escalation of TAK-931 will be based on evaluation of clinical safety and tolerability and guided by accumulating PK data. 3-4 dose cohorts are expected for each dosing schedule.

If the PK from the early cohorts support BID dosing, then study drug administration in subsequent cohorts may transition to a BID dosing schedule.

Drug: TAK-931
TAK-931 oral capsules.

Primary Outcome Measures :
  1. Number and Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Toxicity will be assessed in the first cycle of dosing up to dosing on Cycle 2 Day 1 ]
    DLTs are any of the events specified in the protocol that are considered by the investigator to be at least possibly related to study drug. DLTs will be evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).

  2. Number and Percentage of Participants Reporting Adverse Events (AEs) [ Time Frame: Baseline up to 30-40 days after the last dose of study drug (with last dose at approximately 3 months) ]

Secondary Outcome Measures :
  1. Cmax: Maximum Observed Plasma Concentration for TAK-931 [ Time Frame: Concentrations will be assessed at multiple time points (up to 24 hours postdose ) on Cycle 1 (Days 1 and 7 or Days 1 and 8) ]
  2. Tmax: Time to Reach the Maximum Plasma Concentration for TAK-931 [ Time Frame: Cycle 1: Days 1 and 7 or Days 1 and 8: at multiple time points (up to 24 hours postdose) ]
  3. AUC(0-24): Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours Postdose for TAK-931 Once Daily (QD) Dosing [ Time Frame: Cycle 1: Days 1 and 7 or Days 1 and 8: at multiple time points (up to 24 hours post dose) ]
  4. AUC(0-12): Area Under the Plasma Concentration-Time Curve From Time 0 to 12 Hours Postdose for TAK-931 Twice Daily (BID) Dosing [ Time Frame: Cycle 1: Days 1 and 7 or Days 1 and 8: at multiple time points (up to 24 hours post dose) ]
  5. AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-931 [ Time Frame: Cycle 1: Days 1 and 7 or Days 1 and 8: at multiple time points (up to 24 hours postdose) ]
  6. Change from Baseline in Phosphorylated Minichromosome Maintenance Complex-2 (pMCM2) (Ser40) Levels in Skin [ Time Frame: Skin biopsies will be collected at screening or Cycle 1 Day 1 pre-dose and on any dosing day after 3 consecutive days post-dose ]
  7. Overall Response Rate (ORR) [ Time Frame: From the first dose until complete response [CR] or partial response [PR] as assessed at Cycle 4 Day 1, and then every 3 cycles thereafter through the study completion (approximately 3 months) ]
  8. Progression-free Survival (PFS) [ Time Frame: From the first dose until disease progression or death (approximately 3 months) ]
  9. Duration of Response (DOR) [ Time Frame: Time from participant's initial CR or PR to the time of disease progression (approximately 3 months) ]

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.

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Must have an advanced, nonhematologic solid tumor.
  2. Must have an eastern cooperative oncology group (ECOG) performance status of 0 or 1.
  3. Must have a life expectancy of greater than equal to (>=) 3 months.
  4. Must have the ability to swallow oral medications, willingness to undergo serial skin punch biopsies, and suitable venous access for the study-required PK and pharmacodynamic sampling.
  5. Must have adequate bone marrow, liver, kidney and cardiac functions

Exclusion Criteria:

  1. Must not have serious or uncontrolled medical disorders.
  2. Must not be on medications that may interfere with absorption or excretion of TAK-931
  3. Must not be on any medications that affect normal cardiac or blood pressure responses.
  4. Must not have uncontrolled or significant cardiovascular disease, hypertension or hypotension.

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 identifier (NCT number): NCT02699749

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Kashiwa, Chiba, Japan
Chuo-ku, Tokyo, Japan
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
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Study Director: Study Director Takeda
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Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT02699749    
Other Study ID Numbers: TAK-931-1002 Merge to Takeda
U1111-1181-0269 ( Registry Identifier: WHO )
JapicCTI-163200 ( Registry Identifier: JapicCTI )
First Posted: March 4, 2016    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 for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see 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