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NCT04929223PHASE1Recruiting

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

Hoffmann-La Roche

Start Date

10/22/2021

Completion Date

8/31/2030

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria * 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 Exclusion Criteria * 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

Interventions

DRUG

Inavolisib

DRUG

Bevacizumab

DRUG

Cetuximab

DRUG

Atezolizumab

DRUG

Tiragolumab

DRUG

SY-5609

DRUG

Divarasib

DRUG

FOLFOX

DRUG

FOLFIRI

DIAGNOSTIC_TEST

FoundationOne®Liquid CDx

Interested in This Trial?

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Conditions

Metastatic Colorectal Cancer

Locations

UAB Comprehensive Cancer Center

Birmingham, Alabama 35233

United States

Mayo Clinic Arizona

Phoenix, Arizona 85259

United States

City of Hope Comprehensive Cancer Center

Duarte, California 91010

United States

cCare

Encinitas, California 92024

United States

USC Norris Cancer Center

Los Angeles, California 90033

United States

Cedars-Sinai Medical Center

Los Angeles, California 90048

United States

UCLA

Los Angeles, California 90095

United States

Hoag Memorial Hospital Presbyterian

Newport Beach, California 92663

United States

Stanford Cancer Center

Stanford, California 94305-5820

United States

University of Colorado Cancer Center

Aurora, Colorado 80045

United States

Rocky Mountain Cancer Centers, LLP

Lone Tree, Colorado 80124

United States

Yale Cancer Center

New Haven, Connecticut 06520

United States

Eastern Ct Hema/Onco Assoc

Norwich, Connecticut 06360

United States

Mayo Clinic in Florida

Jacksonville, Florida 32224

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Illinois Cancer Specialists

Arlington Heights, Illinois 60005

United States

Mary Bird Perkins Cancer Ctr

Baton Rouge, Louisiana 70809

United States

Massachusetts General Hospital

Boston, Massachusetts 02114-2621

United States

Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Mayo Clinic Rochester

Rochester, Minnesota 55902

United States

New York Cancer & Blood Specialists - New Hyde Park

New Hyde Park, New York 11042-1116

United States

New York Cancer and Blood Specialists-Central Park Hematology & Oncology

New York, New York 10028

United States

New York Cancer & Blood Specialists

Port Jefferson Station, New York 11776

United States

New York Cancer & Blood Specialists - Bronx

The Bronx, New York 10469-5930

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Hematology Oncology Salem

Salem, Oregon 97301

United States

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee 37203

United States

SCRI Oncology Partners

Nashville, Tennessee 37203

United States

Vanderbilt University Medical Center

Nashville, Tennessee 37232

United States

Texas Oncology - Northeast Texas

Denton, Texas 76201

United States

Lumi Research

Kingwood, Texas 77339

United States

Texas Oncology - Gulf Coast

Webster, Texas 77598-4420

United States

Swedish Cancer Inst.

Seattle, Washington 98104

United States

Medical Oncology Associates

Spokane, Washington 99208

United States

Peter Maccallum Cancer Centre

Melbourne, Victoria 3000

Australia

Princess Margaret Cancer Center

Toronto, Ontario M5G 1X6

Canada

Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

McGill University Health Center

Montreal, Quebec H4A 3J1

Canada

Herlev Hospital, Afdeling for Kræftbehandling, Center for Kræftforskning, Klinisk Forskningsenhed

Herlev, 2730

Denmark

Rigshospitalet, Onkologisk Klinik

København Ø, 2100

Denmark

Charité Universitätsmedizin Berlin

Berlin, 13353

Germany

Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital

Bochum, 44791

Germany

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden

Dresden, 01307

Germany

Universitätsklinikum Düsseldorf

Düsseldorf, 40225

Germany

Asklepios Klinik Altona

Hamburg, 22763

Germany

SLK-Kliniken Heilbronn GmbH;Klinik für Innere Medizin III

Heilbronn, 74078

Germany

Klinikum der Universität München, Campus Großhadern

München, 81377

Germany

Universitätsklinikum Ulm

Ulm, 89081

Germany

Università degli Studi della Campania Luigi Vanvitelli

Naples, Campania 80131

Italy

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, Emilia-Romagna 47014

Italy

Policlinico Universitario Agostino Gemelli IRCCS

Rome, Lazio 00168

Italy

Irccs Istituto Nazionale Dei Tumori (Int)

Milan, Lombardy 20133

Italy

Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda)

Milan, Lombardy 20162

Italy

IRCCS Istituto Oncologico Veneto (IOV)

Padova, Veneto 35128

Italy

Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz

Gdansk, 80-952

Poland

Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii

Krakow, 30-688

Poland

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, 60-569

Poland

Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie

Warsaw, 02-781

Poland

National Cancer Center

Goyang-si, 10408

South Korea

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128

South Korea

Seoul National University Bundang Hospital

Seongnam-si, 13605

South Korea

Samsung Medical Center

Seoul, (0)6351

South Korea

Seoul National University Hospital

Seoul, 03080

South Korea

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Hospital Universitario de Donostia

Donostia / San Sebastian, Guipuzcoa 20080

Spain

Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, Madrid 28222

Spain

Vall d'Hebron Institute of Oncology (VHIO), Barcelona

Barcelona, 08035

Spain

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040

Spain

START Madrid. Centro Integral Oncologico Clara Campal

Madrid, 28050

Spain

Hospital Clínico Universitario de Valencia

Valencia, 46010

Spain

Hospital Clinico Universitario Lozano Blesa

Zaragoza, 50009

Spain

National Cheng Kung University Hospital

Tainan, 00704

Taiwan

Taipei Veterans General Hospital

Taipei, 112201

Taiwan

National Taiwan University Hospital

Zhongzheng Dist., 10048

Taiwan

Addenbrookes Hospital

Cambridge, CB2 0QQ

United Kingdom

Velindre Cancer Centre

Cardiff, CF14 2TL

United Kingdom

Royal Free Hospital

London, NW3 2QG

United Kingdom

Royal Marsden Hospital;Dept of Med-Onc

London, SW3 6JJ

United Kingdom

Sarah Cannon Research Institute

London, W1G 6AD

United Kingdom

Imperial College Healthcare NHS Trust

London, W2 1NY

United Kingdom

The Christie NHS Foundation Trust

Manchester, M20 4BX

United Kingdom

Royal Marsden Hospital

Sutton, SM2 5PT

United Kingdom