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NCT Number: NCT05245968

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

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.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Gastrointestinal Stromal Tumors Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms, Connective Tissue Neoplasms, Connective and Soft Tissue

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Flinders Medical Center, Adelaide, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Pimitespib

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.

Other names: TAS-116

Imatinib

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.

Sunitinib

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.

Primary outcomes

  1. Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib

    Time frame: At the end of Cycle 1 (each cycle is 28 days)

  2. Maximum tolerable dose (MTD) of pimitespib in combination with imatinib

    Time frame: At the end of Cycle 1 (each cycle is 28 days)

  3. Progression-free survival (PFS)

    Time frame: approximately 2 years

Secondary outcomes

  1. Overall survival (OS)

    Time frame: approximately 2 years

  2. Overall response rate (ORR)

    Time frame: approximately 2 years

  3. Disease control rate (DCR)

    Time frame: approximately 2 years

  4. Duration of response (DoR)

    Time frame: approximately 2 years

  5. Adverse event (AE)

    Time frame: approximately 2 years

  6. Adverse drug reaction (ADR)

    Time frame: approximately 2 years

  7. Maximum plasma concentration (Cmax)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  8. Time to reach maximum plasma concentration (Tmax)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  9. Under the plasma concentration-time curve up to the last observable concentration (AUC0-last)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  10. Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  11. λz

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  12. Half-life (T1/2)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  13. Oral clearance (CL/F)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  14. Apparent volume of distribution (Vz/F)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  15. Mean residence time (MRT)

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  16. Accumulation ratio

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

  17. Metabolite ratio

    Time frame: Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

Sponsors and collaborators

Lead sponsor

Taiho Pharmaceutical Co., Ltd.

Industry

Registry information

Official study title

A Phase 1 Study of TAS-116 (Pimitespib) in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumor

Important dates

Study start
2021
Primary completion
2026
Study completion
2026
First posted
Feb 18, 2022
Registry last updated
Jan 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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