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

NCT05245968 · tracked via the Priya Life Science Australia tracker

Sponsor

Taiho Pharmaceutical Co., Ltd

Phase

Phase 1

Started

2021-12-01

Last updated

2026-01-20

Condition(s) studied

Gastrointestinal Stromal Tumors

Investigational drug(s) / intervention(s)

Pimitespib →Imatinib →Sunitinib →

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.

Study 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.

Eligibility

Sex

ALL

Min age

18 Years

Max age

—

Healthy volunteers

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)

Primary outcome measure(s)

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

Trial sites (14)

Facility	City	Region
Flinders Medical Center	Adelaide	Australia
Alfred Health	Melbourne	Australia
Beijing Cancer Hospital	Beijing	China
Fudan University, Shanghai Cancer Center	Shanghai	China
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	Japan
National University Cancer Institute	Singapore	Singapore
Kaohsiung Medical University Hospital	Kaohsiung City	Taiwan
Linkou Chang Gung Memorial Hospital	Linkou District	Taiwan
Taipei Veterans General Hospital	Taipei	Taiwan

On this site

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT05245968 on ClinicalTrials.gov ↗ ← All trials in Australia