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

Gastrointestinal Stromal Tumors Clinical Trial

Official title:

A Phase 1 Study of TAS-116 (Pimitespib) in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumor

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05245968
• Other study ID #: 10058060
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2021
• Est. completion date: December 2025

Study information

• Verified date: April 2024
• Source: Taiho Pharmaceutical Co., Ltd.
• Contact: Drug Information Center
• Phone: +81-3-3294-4527
• Email: n-arimura[@]taiho.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Australia	Flinders Medical Center	Adelaide
Australia	Alfred Health	Melbourne
China	Beijing Cancer Hospital	Beijing
Japan	National Cancer Center Hospital East	Chiba
Japan	Hokkaido University Hospital	Hokkaido
Japan	Kumamoto University Hospital	Kumamoto
Japan	Osaka University Hospital	Osaka
Japan	National Cancer Center Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Singapore	National University Cancer Institute	Singapore
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung
Taiwan	Linkou Chang Gung Memorial Hospital	Linkou
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Pharmaceutical Co., Ltd.

Countries where clinical trial is conducted

Australia,  China,  Japan,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib		At the end of Cycle 1 (each cycle is 28 days)
Primary	Maximum tolerable dose (MTD) of pimitespib in combination with imatinib		At the end of Cycle 1 (each cycle is 28 days)
Primary	Progression-free survival (PFS)		approximately 2 years
Secondary	Overall survival (OS)		approximately 2 years
Secondary	Overall response rate (ORR)		approximately 2 years
Secondary	Disease control rate (DCR)		approximately 2 years
Secondary	Duration of response (DoR)		approximately 2 years
Secondary	Adverse event (AE)		approximately 2 years
Secondary	Adverse drug reaction (ADR)		approximately 2 years
Secondary	Maximum plasma concentration (Cmax)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Time to reach maximum plasma concentration (Tmax)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Under the plasma concentration-time curve up to the last observable concentration (AUC0-last)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	?z		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Half-life (T1/2)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Oral clearance (CL/F)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Apparent volume of distribution (Vz/F)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Mean residence time (MRT)		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Accumulation ratio		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Secondary	Metabolite ratio		Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)