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

Phase 1Active Not RecruitingNCT05245968

Taiho Pharmaceutical Co., Ltd.78 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Gastrointestinal Stromal Tumors

Interventions

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.

ImatinibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

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

...and 4 more locations

Outcomes

Primary Outcomes

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

Secondary Outcomes

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)