A Study of Pimitespib in Combination With Imatinib in Patients With GIST (CHAPTER-GIST-101)

• ClinicalTrials.gov Identifier: NCT05245968
• Recruitment Status: Recruiting
• First Posted: February 18, 2022
• Last Update Posted: June 2, 2023
• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Taiho Pharmaceutical Co., Ltd.

Study Description

Brief Summary:

This study consists of Dose escalation part and Expansion part. In Dose Escalation Part, the maximum tolerated dose of combination of pimitespib and imatinib in patients with gastrointestinal stromal tumors (GIST) who are judged to be refractory to imatinib, estimate the recommended dose, evaluate safety and pharmacokinetics, and observe the antitumor effect. Expansion part consists of 3 arms. In Arm A, the efficacy and safety will be evaluated, which of the combination of pimitespib and imatinib in patients with GIST who have failed imatinib at doses below the MTD determined in Dose Escalation Part. In Arm B, the efficacy and safety of pimitespib monotherapy will be evaluated and the therapeutic effect of imatinib administration after pimitespib will be evaluated in an exploratory manner. In Arm C, the efficacy and safety of sunitinib monotherapy will be evaluated as reference data.

Condition or disease	Intervention/treatment	Phase
Gastrointestinal Stromal Tumors	Drug: Pimitespib; Drug: Imatinib; Drug: Sunitinib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 78 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study of TAS-116 (Pimitespib) in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumor
• Actual Study Start Date: December 1, 2021
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: December 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation Part; Pimitespib in combination with imatinib	Drug: Pimitespib; Pimitespib will be administered orally in 5 consecutive days followed by 2 days off treatment (QD 5) on an empty stomach at least 1 hour before or 2 hours after a meal. The doses in the Dose Escalation Part will be 80, 120 (starting dose), and 160 mg. The doses used in Arm A will be MTD or recommended dose (RD) based on the information, including the safety and the pharmacokinetics (PK) data in the Dose Escalation Part. In Expansion Part-B, pimitespib will be administered with the starting dose of 160 mg daily.; Other Name: TAS-116; Drug: Imatinib; Imatinib will be administered orally, after a meal and large glass of water QD. The doses in Dose Escalation Part will be 400 mg or 300 mg (De-escalation). The doses used in Expansion Part-A will be MTD or RD based on information, including the safety and PK data in the Dose Escalation Part. In Expansion Part-B, imatinib will be administered post after pimitespib discontinuation with the starting dose of 400 mg daily.
Experimental: Expansion Part-A; Pimitespib in combination with imatinib	Drug: Pimitespib; Pimitespib will be administered orally in 5 consecutive days followed by 2 days off treatment (QD 5) on an empty stomach at least 1 hour before or 2 hours after a meal. The doses in the Dose Escalation Part will be 80, 120 (starting dose), and 160 mg. The doses used in Arm A will be MTD or recommended dose (RD) based on the information, including the safety and the pharmacokinetics (PK) data in the Dose Escalation Part. In Expansion Part-B, pimitespib will be administered with the starting dose of 160 mg daily.; Other Name: TAS-116; Drug: Imatinib; Imatinib will be administered orally, after a meal and large glass of water QD. The doses in Dose Escalation Part will be 400 mg or 300 mg (De-escalation). The doses used in Expansion Part-A will be MTD or RD based on information, including the safety and PK data in the Dose Escalation Part. In Expansion Part-B, imatinib will be administered post after pimitespib discontinuation with the starting dose of 400 mg daily.
Experimental: Expansion Part-B; Pimitespib followed by imatinib	Drug: Pimitespib; Pimitespib will be administered orally in 5 consecutive days followed by 2 days off treatment (QD 5) on an empty stomach at least 1 hour before or 2 hours after a meal. The doses in the Dose Escalation Part will be 80, 120 (starting dose), and 160 mg. The doses used in Arm A will be MTD or recommended dose (RD) based on the information, including the safety and the pharmacokinetics (PK) data in the Dose Escalation Part. In Expansion Part-B, pimitespib will be administered with the starting dose of 160 mg daily.; Other Name: TAS-116; Drug: Imatinib; Imatinib will be administered orally, after a meal and large glass of water QD. The doses in Dose Escalation Part will be 400 mg or 300 mg (De-escalation). The doses used in Expansion Part-A will be MTD or RD based on information, including the safety and PK data in the Dose Escalation Part. In Expansion Part-B, imatinib will be administered post after pimitespib discontinuation with the starting dose of 400 mg daily.
Experimental: Expansion Part-C; Sunitinib	Drug: Sunitinib; Sunitinib will be administered orally QD with a starting dose of 50 mg, on a schedule of 4 weeks on treatment followed by 2 weeks off, and will be taken with or without a meal in Expansion Part-C.

Outcome Measures

Primary Outcome Measures :

1. Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
2. Maximum tolerable dose (MTD) of pimitespib in combination with imatinib [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
3. Progression-free survival (PFS) [ Time Frame: approximately 2 years ]

Secondary Outcome Measures :

1. Overall survival (OS) [ Time Frame: approximately 2 years ]
2. Overall response rate (ORR) [ Time Frame: approximately 2 years ]
3. Disease control rate (DCR) [ Time Frame: approximately 2 years ]
4. Duration of response (DoR) [ Time Frame: approximately 2 years ]
5. Adverse event (AE) [ Time Frame: approximately 2 years ]
6. Adverse drug reaction (ADR) [ Time Frame: approximately 2 years ]
7. Maximum plasma concentration (Cmax) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
8. Time to reach maximum plasma concentration (Tmax) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
9. Under the plasma concentration-time curve up to the last observable concentration (AUC0-last) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
10. Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
11. λz [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
12. Half-life (T1/2) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
13. Oral clearance (CL/F) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
14. Apparent volume of distribution (Vz/F) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
15. Mean residence time (MRT) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
16. Accumulation ratio [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
17. Metabolite ratio [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Provided written informed consent
• Histologically confirmed GIST
• Progressed on the basis of imaging during or within 6 months of the last imatinib administration at enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Received treatment with any other line of therapy besides imatinib for advanced GIST; including local surgery and radiotherapy
• A serious illness or medical condition
• Previous or concurrent cancer that is distinct in primary disease or histology from cancer that is being evaluated in this study
• Pregnancy or lactation (including lactation interruption)

Contacts and Locations

Contacts

Contact: Drug Information Center; +81-3-3294-4527; n-arimura@taiho.co.jp

Locations

Australia

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Adelaide, Australia

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Melbourne, Australia

Japan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Chiba, Japan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Hokkaido, Japan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Kumamoto, Japan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Osaka, Japan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Tokyo, Japan

Singapore

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Singapore, Singapore

Taiwan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Kaohsiung, Taiwan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Linkou, Taiwan

A site selected by Taiho Pharmaceutical Co., Ltd.; Recruiting

Taipei, Taiwan

Sponsors and Collaborators

Taiho Pharmaceutical Co., Ltd.

Investigators

• Study Director: Taiho Pharmaceutical Co., Ltd.; Taiho Pharmaceutical Co., Ltd.

More Information

• Responsible Party: Taiho Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05245968
• Other Study ID Numbers: 10058060
• First Posted: February 18, 2022
• Last Update Posted: June 2, 2023
• Last Verified: June 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Taiho provides a platform for accepting researchers' requests for sharing anonymized, patient-level, analyzable datasets from articles published in peer-reviewed journals about the primary results from Taiho-sponsored interventional clinical trials in patients in which the medicine and the indication has received marketing approval from regulatory authorities in the United States, the European Union, and/or Japan on or after January 15, 2018.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html
• Access Criteria: Access to the clinical trial data is contingent upon approval of a proposed study protocol by an independent review panel and the execution of a data-sharing agreement with the researcher.
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Gastrointestinal Stromal Tumors; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Sunitinib; Imatinib Mesylate; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Physiological Effects of Drugs; Growth Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action