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

Taiho Pharma

Status and phase: Active, not recruiting; Phase 1

Conditions: Gastrointestinal Stromal Tumors

Treatments: Drug: Sunitinib; Drug: Pimitespib; Drug: Imatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05245968

10058060

Details and patient eligibility

About

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.

Enrollment: 78 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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78 participants in 4 patient groups

Dose Escalation Part

Experimental group

Description:

Pimitespib in combination with imatinib

Treatment:

Drug: Imatinib

Drug: Pimitespib

Expansion Part-A

Experimental group

Description:

Pimitespib in combination with imatinib

Treatment:

Drug: Imatinib

Drug: Pimitespib

Expansion Part-B

Experimental group

Description:

Pimitespib followed by imatinib

Treatment:

Drug: Imatinib

Drug: Pimitespib

Expansion Part-C

Experimental group

Description:

Sunitinib

Treatment:

Drug: Sunitinib