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

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

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 Overview

• Status: Recruiting
• Conditions: Gastrointestinal Stromal Tumors
• Intervention / Treatment: Drug: Pimitespib; Drug: Imatinib; Drug: Sunitinib

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Drug Information Center; Phone Number: +81-3-3294-4527; Email: n-arimura@taiho.co.jp

Study Locations

• Australia
  • Adelaide, Australia
    • Recruiting
    • Flinders Medical Center
    • Principal Investigator: Amitesh Roy
  • Melbourne, Australia
    • Recruiting
    • Alfred Health
    • Principal Investigator: John R Zalcberg
• China
  • Beijing, China
    • Recruiting
    • Beijing Cancer Hospital
    • Principal Investigator: Lin Shen
• Japan
  • Chiba, Japan
    • Recruiting
    • National Cancer Center Hospital East
    • Principal Investigator: Yoichi Naito
  • Hokkaido, Japan
    • Recruiting
    • Hokkaido University Hospital
    • Principal Investigator: Yoshito Komatsu
  • Kumamoto, Japan
    • Recruiting
    • Kumamoto University Hospital
    • Principal Investigator: Masaaki Iwatsuki
  • Osaka, Japan
    • Recruiting
    • Osaka University Hospital
    • Principal Investigator: Yukinori Kurokawa
  • Tokyo, Japan
    • Recruiting
    • National Cancer Center Hospital
    • Principal Investigator: Hidekazu Hirano
  • Tokyo, Japan
    • Recruiting
    • The Cancer Institute Hospital of Jfcr
    • Principal Investigator: Masato Ozaka
• Singapore
  • Singapore, Singapore
    • Recruiting
    • National University Cancer Institute
    • Principal Investigator: Raghav Sundar
• Taiwan
  • Kaohsiung, Taiwan
    • Recruiting
    • Kaohsiung Medical University Hospital
    • Principal Investigator: Li-Tzong Chen
  • Linkou, Taiwan
    • Recruiting
    • Linkou Chang Gung Memorial Hospital
    • Principal Investigator: Jen-Shi Chen
  • Taipei, Taiwan
    • Recruiting
    • Taipei Veterans General Hospital
    • Principal Investigator: Chueh-Chuan Yen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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 Names: 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 Names: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Dose-limiting toxicity (DLT) of pimitespib in combination with imatinib	At the end of Cycle 1 (each cycle is 28 days)
Maximum tolerable dose (MTD) of pimitespib in combination with imatinib	At the end of Cycle 1 (each cycle is 28 days)
Progression-free survival (PFS)	approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	approximately 2 years
Overall response rate (ORR)	approximately 2 years
Disease control rate (DCR)	approximately 2 years
Duration of response (DoR)	approximately 2 years
Adverse event (AE)	approximately 2 years
Adverse drug reaction (ADR)	approximately 2 years
Maximum plasma concentration (Cmax)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Time to reach maximum plasma concentration (Tmax)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Under the plasma concentration-time curve up to the last observable concentration (AUC0-last)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
λz	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Half-life (T1/2)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Oral clearance (CL/F)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Apparent volume of distribution (Vz/F)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Mean residence time (MRT)	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Accumulation ratio	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)
Metabolite ratio	Multiple time points on Day 1 and Day5 or Day12 of Cycle 1 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Taiho Pharmaceutical Co., Ltd.
• Investigators: Study Director: Taiho Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 17, 2022
• First Submitted That Met QC Criteria: February 17, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: April 1, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Neoplasms, Connective Tissue; Gastrointestinal Stromal Tumors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Sunitinib; Imatinib Mesylate
• Other Study ID Numbers: 10058060

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.
• IPD Sharing Time Frame: https://www.taiho.co.jp/en/science/policy/clinical_trial_information_disclosure_policy/index.html
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No