A Study of Pimitespib in Combination with Imatinib in Patients with GIST (CHAPTER-GIST-101)
- Conditions
- Gastrointestinal Stromal Tumors
- Interventions
- Registration Number
- NCT05245968
- Lead Sponsor
- Taiho Pharmaceutical Co., Ltd.
- 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 available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 78
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Expansion Part-A Pimitespib Pimitespib in combination with imatinib Expansion Part-B Pimitespib Pimitespib followed by imatinib Dose Escalation Part Imatinib Pimitespib in combination with imatinib Dose Escalation Part Pimitespib Pimitespib in combination with imatinib Expansion Part-A Imatinib Pimitespib in combination with imatinib Expansion Part-B Imatinib Pimitespib followed by imatinib Expansion Part-C Sunitinib Sunitinib
- Primary Outcome Measures
Name Time Method Maximum tolerable dose (MTD) of pimitespib in combination with imatinib At the end of Cycle 1 (each cycle is 28 days) Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib At the end of Cycle 1 (each cycle is 28 days) Progression-free survival (PFS) approximately 2 years
- Secondary Outcome Measures
Name Time Method Oral clearance (CL/F) 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) 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) 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) Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) λz Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) Half-life (T1/2) Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) Adverse drug reaction (ADR) approximately 2 years Maximum plasma concentration (Cmax) Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) Overall response rate (ORR) approximately 2 years Duration of response (DoR) approximately 2 years Adverse event (AE) approximately 2 years Overall survival (OS) approximately 2 years Disease control rate (DCR) approximately 2 years Apparent volume of distribution (Vz/F) Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) Mean residence time (MRT) Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) Accumulation ratio Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days) Metabolite ratio Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Trial Locations
- Locations (14)
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, Taiwan
Linkou Chang Gung Memorial Hospital
🇨🇳Linkou, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan