Clinical trial NCT05245968: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Gastrointestinal Stromal Tumors
Lead sponsor: Taiho Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-02-18
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Maximum tolerable dose (MTD) of pimitespib in combination with imatinib
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Progression-free survival (PFS)
timeFrame: approximately 2 years
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: approximately 2 years
measure: Overall response rate (ORR)
timeFrame: approximately 2 years
measure: Disease control rate (DCR)
timeFrame: approximately 2 years
measure: Duration of response (DoR)
timeFrame: approximately 2 years
measure: Adverse event (AE)
timeFrame: approximately 2 years
measure: Adverse drug reaction (ADR)
timeFrame: approximately 2 years
measure: Maximum plasma concentration (Cmax)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Time to reach maximum plasma concentration (Tmax)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Under the plasma concentration-time curve up to the last observable concentration (AUC0-last)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: λz
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Half-life (T1/2)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Oral clearance (CL/F)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Apparent volume of distribution (Vz/F)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Mean residence time (MRT)
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Accumulation ratio
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
measure: Metabolite ratio
timeFrame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: Flinders Medical Center
city: Melbourne
country: Australia
facility: Alfred Health
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Shanghai
country: China
facility: Fudan University, Shanghai Cancer Center
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Singapore
country: Singapore
facility: National University Cancer Institute
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
city: Linkou
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Taiho Pharmaceutical Co., Ltd.
name: Taiho Pharmaceutical Co., Ltd.
role: STUDY_DIRECTOR
References: