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

NCT ID: NCT05245968

Last Updated: 2026-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

78 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2026-12-31

Brief Summary

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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

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Conditions

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Gastrointestinal Stromal Tumors

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Escalation Part

Pimitespib in combination with imatinib

Group Type EXPERIMENTAL

Pimitespib

Intervention Type DRUG

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

Intervention Type DRUG

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.

Expansion Part-A

Pimitespib in combination with imatinib

Group Type EXPERIMENTAL

Pimitespib

Intervention Type DRUG

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

Intervention Type DRUG

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.

Expansion Part-B

Pimitespib followed by imatinib

Group Type EXPERIMENTAL

Pimitespib

Intervention Type DRUG

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

Intervention Type DRUG

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.

Expansion Part-C

Sunitinib

Group Type EXPERIMENTAL

Sunitinib

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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TAS-116

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Taiho Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Taiho Pharmaceutical Co., Ltd.

Role: STUDY_DIRECTOR

Taiho Pharmaceutical Co., Ltd.

Locations

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Flinders Medical Center

Adelaide, , Australia

Site Status

Alfred Health

Melbourne, , Australia

Site Status

Beijing Cancer Hospital

Beijing, , China

Site Status

Fudan University, Shanghai Cancer Center

Shanghai, , China

Site Status

National Cancer Center Hospital East

Chiba, , Japan

Site Status

Hokkaido University Hospital

Hokkaido, , Japan

Site Status

Kumamoto University Hospital

Kumamoto, , Japan

Site Status

Osaka University Hospital

Osaka, , Japan

Site Status

National Cancer Center Hospital

Tokyo, , Japan

Site Status

The Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status

National University Cancer Institute

Singapore, , Singapore

Site Status

Kaohsiung Medical University Hospital

Kaohsiung City, , Taiwan

Site Status

Linkou Chang Gung Memorial Hospital

Linkou District, , Taiwan

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Countries

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Australia China Japan Singapore Taiwan

Other Identifiers

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10058060

Identifier Type: -

Identifier Source: org_study_id

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