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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose Escalation Part | Experimental | Pimitespib in combination with imatinib |
|
| Expansion Part-A | Experimental | Pimitespib in combination with imatinib |
|
| Expansion Part-B | Experimental | Pimitespib followed by imatinib |
|
| Expansion Part-C | Experimental | Sunitinib |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival (OS) | approximately 2 years | |
| Overall response rate (ORR) | approximately 2 years | |
| Disease control rate (DCR) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Taiho Pharmaceutical Co., Ltd. | Taiho Pharmaceutical Co., Ltd. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Flinders Medical Center | Adelaide | Australia | ||||
| Alfred Health |
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.
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.
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|
|
| 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. |
|
| 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) |
| Melbourne |
| Australia |
| Beijing Cancer Hospital | Beijing | China |
| Fudan University, Shanghai Cancer Center | Shanghai | China |
| National Cancer Center Hospital East | Chiba | Japan |
| Hokkaido University Hospital | Hokkaido | Japan |
| Kumamoto University Hospital | Kumamoto | Japan |
| Osaka University Hospital | Osaka | Japan |
| National Cancer Center Hospital | Tokyo | Japan |
| The Cancer Institute Hospital of JFCR | Tokyo | Japan |
| National University Cancer Institute | Singapore | Singapore |
| Kaohsiung Medical University Hospital | Kaohsiung City | Taiwan |
| Linkou Chang Gung Memorial Hospital | Linkou District | Taiwan |
| Taipei Veterans General Hospital | Taipei | Taiwan |
| ID | Term |
|---|---|
| D046152 | Gastrointestinal Stromal Tumors |
| ID | Term |
|---|---|
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
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| ID | Term |
|---|---|
| C000596495 | TAS-116 |
| D000068877 | Imatinib Mesylate |
| D000077210 | Sunitinib |
| ID | Term |
|---|---|
| D001549 | Benzamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D001565 | Benzoates |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011743 | Pyrimidines |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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