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: April 2, 2024
• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Information provided by (Responsible Party): Taiho Pharmaceutical Co., Ltd.

Tracking Information

• First Submitted Date: January 17, 2022
• First Posted Date: February 18, 2022
• Last Update Posted Date: April 2, 2024
• Actual Study Start Date: December 1, 2021
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 17, 2022)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 17, 2022)

• Overall survival (OS) [ Time Frame: approximately 2 years ]
• Overall response rate (ORR) [ Time Frame: approximately 2 years ]
• Disease control rate (DCR) [ Time Frame: approximately 2 years ]
• Duration of response (DoR) [ Time Frame: approximately 2 years ]
• Adverse event (AE) [ Time Frame: approximately 2 years ]
• Adverse drug reaction (ADR) [ Time Frame: approximately 2 years ]
• Maximum plasma concentration (Cmax) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
• 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) ]
• 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) ]
• 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) ]
• λz [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
• Half-life (T1/2) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
• Oral clearance (CL/F) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
• 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) ]
• Mean residence time (MRT) [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
• Accumulation ratio [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]
• Metabolite ratio [ Time Frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Pimitespib in Combination With Imatinib in Patients With GIST (CHAPTER-GIST-101)
• Official Title: A Phase 1 Study of TAS-116 (Pimitespib) in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumor
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Gastrointestinal Stromal Tumors

Intervention

• 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.
• 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.

Study Arms

• Experimental: Dose Escalation Part
  Pimitespib in combination with imatinib
  Interventions:

  • Drug: Pimitespib
  • Drug: Imatinib
• Experimental: Expansion Part-A
  Pimitespib in combination with imatinib
  Interventions:

  • Drug: Pimitespib
  • Drug: Imatinib
• Experimental: Expansion Part-B
  Pimitespib followed by imatinib
  Interventions:

  • Drug: Pimitespib
  • Drug: Imatinib
• Experimental: Expansion Part-C
  Sunitinib
  Intervention: Drug: Sunitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 17, 2022): 78
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Provided written informed consent
• Histologically confirmed GIST
• Has radiographic progression based on RECIST 1.1 during or within 6 months of the last imatinib administration at enrollment. If surgery/radiotherapy has been performed, radiographic progression based on RECIST 1.1 with imatinib must have been observed after the last surgery /radiotherapy
• Has at least one measurable lesion based on the RECIST version 1.1, except lymph nodes (not dependent on size), which should be chosen as nontarget lesions;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria:

• Corrected visual acuity < 0.5 (using the International Visual Acuity Measurement Standard) for both eyes
• Received treatment with any other line of therapy besides imatinib for advanced GIST
• History of total gastrectomy and/or whole resection of the small intestine
• 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. However, any previous cancer curatively treated > 5 years before the enrollment can be eligible
• Pregnancy or lactation (including lactation interruption)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Australia, China, Japan, Singapore, Taiwan

Administrative Information

• NCT Number: NCT05245968
• Other Study ID Numbers: 10058060
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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
• Supporting Materials: 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/

• Current Responsible Party: Taiho Pharmaceutical Co., Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taiho Pharmaceutical Co., Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Taiho Pharmaceutical Co., Ltd.
• Verification Date: April 2024