A Study to Evaluate TAK-931 in Participants With Advanced Nonhematologic Tumors

NCT ID: NCT02699749

Last Updated: 2021-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-24
• Study Completion Date: 2019-12-21

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.

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.

Conditions

Nonhematologic Neoplasms, Advanced

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

TAK-931

Intervention Type: DRUG

TAK-931 oral capsules.

Interventions

TAK-931

TAK-931 oral capsules.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed diagnosis of an advanced, nonhematologic/solid tumor (with the exception of primary brain tumor).

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

3. For whom no effective standard therapy is available.

4. Life expectancy of greater than or equal to (>=3) months.

5. Female participants who:

• Are postmenopausal (natural amenorrhea and not due to other medical reasons) for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 30 days after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)

Male participants, even if surgically sterilized (example, status postvasectomy), who:

• Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR
• Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [example, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
• Agree not to donate sperm during this study and for 120 days after receiving their last dose of study drug.

6. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.

7. Ability to swallow oral medications, willingness to undergo serial skin punch biopsies, and suitable venous access for the study-required PK and pharmacodynamic sampling.

8. Clinical laboratory values as specified below within 28 days before the first dose of study drug:

• Bone marrow reserve consistent with absolute neutrophil count (ANC) >=1500 per millimeter cube (/mm˄3), platelet count >=100,000/mm˄3, and hemoglobin >=9 per gram deciliter (g/dL).
• Total bilirubin must be less than (<) 1.5 times the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be 3 <=ULN. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of hepatocellular carcinoma, biliary tract cancer, or metastatic disease in liver.
• Serum albumin >=3.0 g/dL.
• Serum creatinine <1.5 times the institutional ULN or creatinine clearance based on the Cockcroft-Gault estimate >=50 milliliter per minute (mL/minute) for participants with serum creatinine concentrations above institutional limits.

9. Left ventricular ejection fraction (LVEF) greater than (>) 50 percent (%) as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks before receiving the first dose of study drug.

10. Recovered (that is, <=Grade 1 toxicity) from the reversible effects of prior anticancer therapy. Participants with ongoing toxicities at baseline may be eligible; however, any Grade 2 baseline toxicity (except for alopecia) should be discussed with the medical monitor.

Exclusion Criteria

1. 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 within 14 days before the first dose of study drug.

3. Treatment with any investigational products within 30 days before the first dose of study drug.

4. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug.

5. Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

6. History of any of the following within the last 3 months before administration of the first dose of study drug:

• Ischemic myocardial event including angina requiring therapy and artery revascularization procedures, myocardial infarction, and unstable symptomatic ischemic heart disease.
• Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures.
• Thromboembolic events (example, deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events).
• Significant, uncontrolled cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
• Use of rate control drugs for arrhythmias (including beta blockers [such as metoprolol],acetylcholine, digoxin, and non-dihydropyridine calcium channel blockers diltiazem and verapamil).
• Placement of a pacemaker for control of cardiac rhythm.
• Requirement for inotropic support (including digoxin).
• New York Heart Association (NYHA) Class II to IV heart failure.
• Any other cardiac condition that in the opinion of the investigator could pose an additional risk for the participation in the study (example, pericardial effusion or restrictive cardiomyopathy).
• Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval >480 millisecond (msec), or history of congenital, long QT syndrome, or torsades de pointes).

7. With any of the following blood pressure conditions:

• History of orthostatic hypotension or syncope that required medical intervention. Orthostatic hypotension is defined as a 20 millimeter of mercury (mmHg) fall in systolic blood pressure and/or a 10 mmHg fall in diastolic blood pressure within 2 to 5 minutes of quiet standing immediately after a 5-minute period of supine rest.
• Postural orthostatic tachycardia syndrome (POTS) or postural tachycardia syndrome (defined as an increase in heart rate of >30 beats per minute over baseline after 10 minutes of quiet standing).
• Hypertension that is unstable or not controlled by medication.

8. Seizures requiring antiepileptic treatment.

9. History of uncontrolled brain metastasis unless:

• Previously treated with surgery, whole-brain radiation, or stereotactic radiosurgery.
• Stable disease for ≥60 days, without steroid use (or stable steroid dose established for ≥28 days before the first dose of TAK-931).

10. Symptomatic and/or progressive central nervous system (CNS) metastases.

11. Ongoing medical conditions, such as acute exacerbations of chronic illnesses, serious infections, or major surgery within 4 weeks before receiving the first dose of study drug.

12. Known history of human immunodeficiency virus (HIV) infection.

13. Known hepatitis B (HBV) surface antigen seropositive or detectable hepatitis C (HCV) infection viral load. Note: Participants who have positive hepatitis B core antibody or hepatitis B surface antibody can be enrolled but must have an undetectable hepatitis B viral load. Participants who have positive hepatitis C antibody must have an undetectable hepatitis C viral load.

14. Known gastrointestinal (GI) disease or GI procedure that could interfere with the GI absorption of study drug, such as total gastrectomy or GI conditions that could substantially modify gastric pH.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Kashiwa, Chiba, Japan

Chuo-ku, Tokyo, Japan

Countries

Japan

References

Kuboki Y, Shimizu T, Yonemori K, Kojima T, Kondo S, Koganemaru S, Iwasa S, Harano K, Koyama T, Lu V, Zhou X, Niu H, Yanai T, Garcia-Ribas I, Doi T, Yamamoto N. Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Inhibitor, in Patients with Advanced Solid Tumors: A Phase I First-in-Human Study. Cancer Res Commun. 2022 Nov 14;2(11):1426-1435. doi: 10.1158/2767-9764.CRC-22-0277. eCollection 2022 Nov.

Reference Type: DERIVED

PMID: 36970056 (View on PubMed)

Martin JC, Sims JR, Gupta A, Bakin AV, Ohm JE. WEE1 inhibition augments CDC7 (DDK) inhibitor-induced cell death in Ewing sarcoma by forcing premature mitotic entry and mitotic catastrophe. Cancer Res Commun. 2022 Jun;2(6):471-482. doi: 10.1158/2767-9764.crc-22-0130. Epub 2022 Jun 20.

Reference Type: DERIVED

PMID: 36338546 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

U1111-1181-0269

Identifier Type: REGISTRY

Identifier Source: secondary_id

JapicCTI-163200

Identifier Type: REGISTRY

Identifier Source: secondary_id

TAK-931-1002 Merge to Takeda

Identifier Type: -

Identifier Source: org_study_id