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

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ClinicalTrials.gov Identifier: NCT05245968
Recruitment Status : Recruiting
First Posted : February 18, 2022
Last Update Posted : April 2, 2024
Sponsor:
Information provided by (Responsible Party):
Taiho Pharmaceutical Co., Ltd.

Study Description
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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.

Condition or disease Intervention/treatment Phase
Gastrointestinal Stromal Tumors Drug: Pimitespib Drug: Imatinib Drug: Sunitinib Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 78 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of TAS-116 (Pimitespib) in Combination With Imatinib in Patients With Advanced Gastrointestinal Stromal Tumor
Actual Study Start Date : December 1, 2021
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Dose Escalation Part
Pimitespib in combination with imatinib
 Drug: 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.
Other Name: TAS-116

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.
Experimental: Expansion Part-A
Pimitespib in combination with imatinib
 Drug: 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.
Other Name: TAS-116

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.
Experimental: Expansion Part-B
Pimitespib followed by imatinib
 Drug: 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.
Other Name: TAS-116

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.
Experimental: Expansion Part-C
Sunitinib
 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.


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05245968


Contacts
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Contact: Drug Information Center +81-3-3294-4527 n-arimura@taiho.co.jp

Locations
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Australia
Flinders Medical Center Recruiting
Adelaide, Australia
Principal Investigator: Amitesh Roy         
Alfred Health Recruiting
Melbourne, Australia
Principal Investigator: John R Zalcberg         
China
Beijing Cancer Hospital Recruiting
Beijing, China
Principal Investigator: Lin Shen         
Japan
National Cancer Center Hospital East Recruiting
Chiba, Japan
Principal Investigator: Yoichi Naito         
Hokkaido University Hospital Recruiting
Hokkaido, Japan
Principal Investigator: Yoshito Komatsu         
Kumamoto University Hospital Recruiting
Kumamoto, Japan
Principal Investigator: Masaaki Iwatsuki         
Osaka University Hospital Recruiting
Osaka, Japan
Principal Investigator: Yukinori Kurokawa         
National Cancer Center Hospital Recruiting
Tokyo, Japan
Principal Investigator: Hidekazu Hirano         
The Cancer Institute Hospital of JFCR Recruiting
Tokyo, Japan
Principal Investigator: Masato Ozaka         
Singapore
National University Cancer Institute Recruiting
Singapore, Singapore
Principal Investigator: Raghav Sundar         
Taiwan
Kaohsiung Medical University Hospital Recruiting
Kaohsiung, Taiwan
Principal Investigator: Li-Tzong Chen         
Linkou Chang Gung Memorial Hospital Recruiting
Linkou, Taiwan
Principal Investigator: Jen-Shi Chen         
Taipei Veterans General Hospital Recruiting
Taipei, Taiwan
Principal Investigator: Chueh-Chuan Yen         
Sponsors and Collaborators
Taiho Pharmaceutical Co., Ltd.
Investigators
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Study Director: Taiho Pharmaceutical Co., Ltd. Taiho Pharmaceutical Co., Ltd.
More Information
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Responsible Party: Taiho Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT05245968    
Other Study ID Numbers: 10058060
First Posted: February 18, 2022    Key Record Dates
Last Update Posted: April 2, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Taiho provides a platform for accepting researchers' requests for sharing anonymized, patient-level, analyzable datasets from articles published in peer-reviewed journals about the primary results from Taiho-sponsored interventional clinical trials in patients in which the medicine and the indication has received marketing approval from regulatory authorities in the United States, the European Union, and/or Japan on or after January 15, 2018.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html
Access Criteria: Access to the clinical trial data is contingent upon approval of a proposed study protocol by an independent review panel and the execution of a data-sharing agreement with the researcher.
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gastrointestinal Stromal Tumors
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Sunitinib
Imatinib Mesylate
 Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Tyrosine Kinase Inhibitors