A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)

Официальное название

A Phase I/Ib Global, Multicenter, Open-label Umbrella Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)

Обзор

This open-label, exploratory study is designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or combinations, in participants with metastatic colorectal cancer (mCRC) whose tumors are biomarker positive as per treatment arm-specific definition. Eligible participants with mCRC will be enrolled into specific treatment arms based on their biomarker assay results.

Вмешательства

• Препарат Inavolisib
  Inavolisib will be administered orally as per schedule specified in the respective arms.
• Препарат Bevacizumab
  Bevacizumab IV will be administered as per schedule specified in the respective arm.
• Препарат Cetuximab
  Cetuximab IV will be administered as per schedule specified in the respective arm.
• Препарат Atezolizumab
  Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.
• Препарат Tiragolumab
  Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.
• Препарат SY-5609
  SY-5609 will be administered by mouth as per schedule specified in the respective arm.
• Препарат Divarasib
  Divarasib will be administered orally as per schedule specified in the respective arms.
• Препарат FOLFOX
  FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.
• Препарат FOLFIRI
  FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.
• Диагностический тест FoundationOne®Liquid CDx
  FoundationOne®Liquid CDx is used to identify presence of genomic alterations for participant cohort assignment.

Первичные конечные точки

• Objective Response Rate [Срок оценки: Approximately 84 months]

Вторичные конечные точки (6)

• Duration of Response [Срок оценки: Approximately 84 months]
• Disease Control Rate [Срок оценки: Approximately 84 months]
• Percentage of Participants with Adverse Events (AEs) [Срок оценки: Approximately 84 months]
• Plasma Concentrations of Divarasib [Срок оценки: At pre-defined intervals from first administration of study drug up to approximately 84 months]
• Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFOX [Срок оценки: Approximately 84 months]
• Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFIRI [Срок оценки: Approximately 84 months]

Критерии участия

Критерии включения

• Signed cohort-specific Informed Consent Form
• Age >= 18 years at time of signing Informed Consent Form
• Biomarker eligibility as determined by:

• A validated test approved by local health authorities for detection of the specified biomarkers/mutations.
• A validated test performed at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA) -certified or equivalently accredited diagnostic laboratory using a validated test for detection of the specified biomarkers.
• Prior test results completed before signing cohort-specific Informed Consent Form or local test results generated prior to or during screening, and availability of a full report of the testing results OR
• Blood-based FoundationOne Liquid CDx biomarker eligibility test result generated prior to or during screening or, in case of re-enrollment after treatment discontinuation, prior to starting a new anti-cancer therapy.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of <= 1
• Life expectancy >= 3 months, as determined by the investigator
• Histologically confirmed adenocarcinoma originating from the colon or rectum
• Metastatic disease
• Prior therapies for metastatic disease
• Ability to comply with the study protocol, in the investigators judgment
• Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Baseline tumor tissue samples will be collected from all participants for exploratory biomarker research
• Adequate hematologic and organ function within 14 days prior to initiation of study treatment
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Критерии исключения

• Current participation or enrollment in another interventional clinical trial. Participants who are participating in the follow-up period of an interventional clinical trial are eligible for the study.
• Any systemic anti-cancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of study treatment
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Pregnant or breastfeeding, or intending to become pregnant during the study
• History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
• Severe infection within 4 weeks prior to initiation of study treatment or any active infection that, in the opinion of the investigator, could impact patient safety
• Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of study treatment
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
• Uncontrolled tumor-related pain
• Uncontrolled or symptomatic hypercalcemia
• Clinically significant and active liver disease
• Negative HIV test at screening, with the following exception: Participants with a positive HIV test at screening are eligible provided they are stable on anti-retroviral therapy for at least 4 weeks, have a CD4 count greater than or equal to 200/uL, have an undetectable viral load, and have not had a history of opportunistic infection attributable to AIDS within the last 12 months.
• Symptomatic, untreated, or actively progressing CNS metastases
• History of leptomeningeal disease or carcinomatous meningitis
• History of malignancy other than CRC within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
• Any other disease, unresolved toxicity from prior therapy, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the participant at high risk from treatment complications
• Requirement for treatment with any medicinal product that contraindicates the use of any of the study treatments, may interfere with the planned treatment, affects participant compliance, or puts the patient at higher risk for treatment-related complications

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 · 35 центров

• UAB Comprehensive Cancer Center — Birmingham
• Mayo Clinic Arizona — Phoenix
• City of Hope Comprehensive Cancer Center — Duarte
• cCare — Encinitas
• USC Norris Cancer Center — Los Angeles
• Cedars-Sinai Medical Center — Los Angeles
• UCLA — Los Angeles
• Hoag Memorial Hospital Presbyterian — Newport Beach
• … и ещё 27 центров

Германия · 8 центров

• Charité Universitätsmedizin Berlin — Berlin
• Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital — Bochum
• Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden — Dresden
• Universitätsklinikum Düsseldorf — Düsseldorf
• Asklepios Klinik Altona — Hamburg
• SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III — Heilbronn
• Klinikum der Universität München, Campus Großhadern — München
• Universitätsklinikum Ulm — Ulm

Великобритания · 8 центров

• Addenbrookes Hospital — Cambridge
• Velindre Cancer Centre — Cardiff
• Royal Free Hospital — London
• Royal Marsden Hospital;Dept of Med-Onc — London
• … и ещё 4 центра

South Korea · 7 центров

• National Cancer Center — Goyang-si
• Chonnam National University Hwasun Hospital — Jeollanam-do
• Seoul National University Bundang Hospital — Seongnam-si
• Samsung Medical Center — Seoul
• Seoul National University Hospital — Seoul
• Severance Hospital, Yonsei University Health System — Seoul
• Asan Medical Center — Seoul

Испания · 7 центров

• Hospital Universitario de Donostia — Donostia / San Sebastian
• Hospital Universitario Puerta de Hierro - Majadahonda — Majadahonda
• Vall d'Hebron Institute of Oncology (VHIO), Barcelona — Barcelona
• START Madrid-FJD, Hospital Fundacion Jimenez Diaz — Madrid
• START Madrid. Centro Integral Oncologico Clara Campal — Madrid
• Hospital Clínico Universitario de Valencia — Valencia
• Hospital Clinico Universitario Lozano Blesa — Zaragoza

Италия · 6 центров

• Università degli Studi della Campania Luigi Vanvitelli — Naples
• Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS — Meldola
• Policlinico Universitario Agostino Gemelli IRCCS — Rome
• Irccs Istituto Nazionale Dei Tumori (Int) — Milan
• Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda) — Milan
• IRCCS Istituto Oncologico Veneto (IOV) — Padova

Польша · 4 центра

• Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz — Gdansk
• Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii — Krakow
• Uniwersytecki Szpital Kliniczny w Poznaniu — Poznan
• Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie — Warsaw

Канада · 3 центра

• Princess Margaret Cancer Center — Toronto
• Jewish General Hospital — Montreal
• McGill University Health Center — Montreal

Тайвань · 3 центра

• National Cheng Kung University Hospital — Tainan
• Taipei Veterans General Hospital — Taipei
• National Taiwan University Hospital — Zhongzheng Dist.

Дания · 2 центра

• Herlev Hospital, Afdeling for Kræftbehandling, Center for Kræftforskning, Klinisk Forsknin — Herlev
• Rigshospitalet, Onkologisk Klinik — København Ø

Австралия · 1 центр

• Peter Maccallum Cancer Centre — Melbourne

Идентификаторы

NCT: NCT04929223 · WO42758 · 2021-001207-33 · 2023-505163-37-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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