(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

Официальное название

A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors

Обзор

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 482 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for Gastrointestinal Stromal Tumors (GIST) and 2) evaluating the potential for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner. This study also contains two substudies: 1) a drug-drug interactions (DDI) substudy will investigate the potential for CGT9486 to be a Cytochrome P450 (CYP)3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST and 2) a substudy intended to test the efficacy of bezuclastinib and sunitinib as first-line (1L) treatment of GIST in approximately 40 participants with KIT exon 9 mutations and no prior systemic therapy (with the exception of up to 10 subjects with ongoing imatinib therapy of ≤4 weeks).

Вмешательства

• Препарат CGT9486
  Participants will receive CGT9486 orally until study stopping rules are met.
• Препарат CGT9486
  Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
• Препарат Sunitinib
  Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
• Препарат Sunitinib
  Participants will receive sunitinib orally until study stopping rules are met.
• Препарат Midazolam
  Participants will receive a single-dose of midazolam on Day 1 and Day 16
• Препарат CGT9486
  Participants will receive CGT9486 orally starting on Day 2 until study stopping rules are met.
• Препарат Sunitinib
  Participants will receive CGT9486 until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
• Препарат CGT9486
  Participants will receive sunitinib until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
• Препарат Sunitinib
  Participants will receive sunitinib orally starting on Day 16 until study stopping rules are met.

Первичные конечные точки

• Part 1a - pharmacokinetics - Cmax [Срок оценки: 16 days]
• Part 1a - pharmacokinetics - AUC [Срок оценки: 16 days]
• Part 1b - pharmacokinetics - Cmax [Срок оценки: 14 days]
• Part 1b - pharmacokinetics - AUC [Срок оценки: 14 days]
• Part 1b - pharmacokinetics - Tmax [Срок оценки: 14 days]
• Part 2 - Progression Free Survival (PFS) [Срок оценки: Approximately 48 months]
• DDI Substudy - pharmacokinetics - AUC [Срок оценки: 16 days]
• DDI Substudy - pharmacokinetics - Cmax [Срок оценки: 14 days]

Вторичные конечные точки (10)

• All Study Parts - observing the safety of each treatment regimen. [Срок оценки: Approximately 48 months]
• All Study Parts - observing the safety of each treatment regimen. [Срок оценки: Approximately 48 months]
• All Study Parts - observing the safety of each treatment regimen. [Срок оценки: Approximately 48 months]
• All Study Parts - observing the safety of each treatment regimen. [Срок оценки: Approximately 48 months]
• Part 1a, Part 1b, Part 2 - Overall Survival (OS) [Срок оценки: Approximately 48 months]
• Part 1a, Part 1b, Part 2 - Objective Response Rate (ORR) [Срок оценки: Approximately 48 months]
• Part 1a, Part 1b, Part 2 - Disease Control Rate (DCR) [Срок оценки: Approximately 48 months]
• Part 1a, Part 1b. Part 2 - Time to response (TTR) [Срок оценки: Approximately 48 months]
• Part 1a, Part 1b, Part 2 - Duration of Response (DOR) [Срок оценки: Approximately 48 months]
• Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30) [Срок оценки: Approximately 48 months]

Критерии участия

Критерии включения

• Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization. (GIST 1L Substudy: must have documented mutation in KIT Exon 9 with an available molecular pathology report; archival or fresh tumor tissue sample will be required)
• Documented disease progression on or intolerance to imatinib (Part 1a, Part 1b, Part 2, DDI Substudy)
• Subjects must have received the following treatment:

• DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST
• Part 1b: Treatment with ≥2 prior TKI for GISTs
• Part 2: Prior treatment with imatinib only
• GIST 1L Substudy: No prior systemic therapy for GIST including adjuvant therapy. Exception: up to 10 subjects with ongoing imatinib therapy of ≤4 weeks
• Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2, GIST 1L Substudy)
• Eastern Cooperative Oncology Group (ECOG) Status

• 0 to 2 (Part 1a, Part 1b, Part 2, DDI Substudy)
• 0 to 1 (GIST 1L Substudy)
• Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits

Критерии исключения

• Known Platelet-Derived Growth Factor Receptor (PDGFR) driving mutations or known succinate dehydrogenase deficiency (Part 1a, Part 1b, Part 2, DDI Substudy)
• Clinically significant cardiac disease
• Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug (Part 1a, Part 1b, Part 2, DDI Substudy)
• Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption
• Any active bleeding excluding hemorrhoidal or gum bleeding
• Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody.
• Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
• Received strong CYP3A4 inhibitors or inducers (Part 1a, Part 1b, Part 2, DDI Substudy)
• Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 36 центров

• University of Alabama at Birmingham — Birmingham
• Mayo Clinic — Scottsdale
• University of Arizona- Cancer Center — Tucson
• City of Hope — Duarte
• University of California, Los Angeles (UCLA) — Los Angeles
• University of California, San Diego (UCSD) — San Diego
• University of California, San Francisco — San Francisco
• University of Colorado Denver — Denver
• … и ещё 28 центров

Италия · 12 центров

• Centro Riferimento Oncologico - Aviano — Aviano
• IRCCS Azienda Ospedaliero-Universitaria di Bologna - Policlinico di Sant'Orsola — Bologna
• ASST degli Spedali Civili di Brescia — Brescia
• IRCCS La Fondazione e l'Istituto di Candiolo — Candiolo
• Azienda Ospedaliero-Universitaria Careggi — Florence
• Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" — Meldola
• Fondazione IRCCS Istituto Nazionale dei Tumori — Milan
• Istituto Europeo di Oncologia — Milan
• … и ещё 4 центра

Испания · 11 центров

Список центров уточняется — проверьте первичный протокол.

Франция · 8 центров

• Institut Bergonie — Bordeaux
• Centre Oscar Lambret — Lille
• Centre Leon Berard — Lyon
• AP-HM - Hôpital de la Timone — Marseille
• Centre Eugene Marquis — Rennes
• ICO St-Herblain — Saint-Herblain
• CHU de Toulouse - Hospital Rangueil — Toulouse
• Gustave Roussy — Villejuif

Великобритания · 7 центров

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Германия · 6 центров

• Helios Klinikum Bad Saarow — Bad Saarow
• Helios Klinikum Berlin-Buch — Berlin
• Universitaetsklinikum Essen — Essen
• Universitaetsklinikum Hamburg-Eppendorf — Hamburg
• Medizinische Hochschule Hannover- Urology Oncology — Hanover
• Universitaetsmedizin Mannheim — Mannheim

South Korea · 5 центров

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Тайвань · 5 центров

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Канада · 4 центра

• Alberta Health Services Cross Cancer Institute — Edmonton
• Princess Margaret Hospital — Toronto
• Tom Baker Cancer Center — Calgary
• Universite de Montreal - Hopital Maisonneuve-Rosemont (HMR) — Montreal

Нидерланды · 4 центра

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Польша · 4 центра

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Бразилия · 3 центра

• Hospital das Clinicas da Universidade Estadual de Campinas (UNICAMP) — Campinas
• lnstituto Nacional de Cancer - INCA — Rio de Janeiro
• CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia — São Paulo

Чехия · 3 центра

• Masarykuv onkologicky ustav — Brno
• Fakultni nemocnice Hradec Kralove — Hradec Králové
• Fakultni nemocnice Olomouc - Oncology clinic — Olomouc

Гонконг · 3 центра

• Humanity & Health Clinical Trial Centre — Central
• Hong Kong United Oncology Centre — Jordon
• Prince of Wales Hospital — Shatin

Мексика · 3 центра

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Аргентина · 2 центра

• Instituto Alexander Fleming — Buenos Aires
• Instituto Oncologico de Cordoba (IONC) — Córdoba

Австралия · 2 центра

• Sir Charles Gairdner Hospital — Nedlands
• Bankstown-Lidcombe Hospital — Bankstown

Чили · 2 центра

• Instituto Oncologico FALP — Santiago
• Centro de Oncologia de Precision, Universidad Mayor — Santiago

Норвегия · 2 центра

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Швеция · 2 центра

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Дания · 1 центр

• Aarhus University Hospital — Aarhus

Венгрия · 1 центр

• Debreceni Egyetem, Klinikai Központ, Onkológiai Klinika — Debrecen

Идентификаторы

NCT: NCT05208047 · CGT9486-21-301

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗