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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04929223
Other study ID # WO42758
Secondary ID
Status Active, not recruiting
Phase Phase 1
First received
Last updated
Start date October 22, 2021
Est. completion date April 15, 2026

Study information

Verified date June 2024
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 422
Est. completion date April 15, 2026
Est. primary completion date September 15, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria - Signed cohort-specific Informed Consent Form - Age >= 18 years at time of signing Informed Consent Form - Biomarker eligibility as determined at a College of American Pathologists/clinical laboratory improvement amendments (CAP/CLIA)-certified or equivalently accredited diagnostic laboratory using a validated test - 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 patients 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. Patients 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: Patients 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 patient 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 patient compliance, or puts the patient at higher risk for treatment-related complications

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Inavolisib
Inavolisib will be administered orally as per schedule specified in the respective arms.
Bevacizumab
Bevacizumab IV will be administered as per schedule specified in the respective arm.
Cetuximab
Cetuximab IV will be administered as per schedule specified in the respective arm.
Atezolizumab
Atezolizumab IV infusion will be administered as per schedule specified in the respective arm.
Tiragolumab
Tiragolumab IV infusion will be administered as per schedule specified in the respective arm.
SY-5609
SY-5609 will be administered by mouth as per schedule specified in the respective arm.
Divarasib
Divarasib will be administered orally as per schedule specified in the respective arms.
FOLFOX
FOLFOX (5-fluorouracil, leucovorin, oxaliplatin) IV will be administered as per schedule specified in the respective arm.
FOLFIRI
FOLFIRI (leucovorin, 5-fluorouracil, irinotecan) IV will be administered as per schedule specified in the respective arm.

Locations

Country Name City State
Australia Peter Maccallum Cancer Centre Melbourne Victoria
Canada Princess Margaret Cancer Center Toronto Ontario
Denmark Rigshospitalet, Onkologisk Klinik; Klinisk Forskningsenhed København Ø
Germany Charité Universitätsmedizin Berlin; Hämatologie/Onkologie und Tumorimmunologie Berlin
Germany Katholisches Klinikum Bochum gGmbH - St. Josef-Hospital; Klinik für Hämatologie und Onkologie Bochum
Germany Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden; Klinik und Poliklinik Dresden
Germany Universitätsklinikum Düsseldorf; Klinik für Gastroenterologie Infektologie u. Hepatologie Düsseldorf
Germany Asklepios Klinik Altona; Hämatologie, Onkologie, Palliativmedizin und Rheumatologie Hamburg
Germany SLK-Kliniken Heilbronn GmbH; Klinik für Innere Medizin III; Schwerpunkt Häma./Onko./Palliativm. Heilbronn
Germany Klinikum der Universität München, Campus Großhadern; Medizinische Klinik und Poliklinik III München
Germany Universitätsklinikum Ulm; Zentrum für Innere Medizin Klinik für Innere Medizin I Ulm
Italy Azienda Socio Sanitaria Territoriale Niguarda (Ospedale Niguarda Ca' Granda); Oncologico -Onc.Falck Milano Lombardia
Italy Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1 Milano Lombardia
Italy Università degli Studi della Campania Luigi Vanvitelli Napoli Campania
Italy IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Prima Padova Veneto
Italy Policlinico Universitario Agostino Gemelli IRCCS; UOS Fase 1 Roma Lazio
Korea, Republic of National Cancer Center Goyang-si
Korea, Republic of Chonnam National University Hwasun Hospital Jeollanam-do
Korea, Republic of Seoul National University Bundang Hospital Seongnam-si
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Poland Szpital Uniwersytecki w Krakowie, Oddzia? Kliniczny Kliniki Onkologii Kraków
Poland Uniwersytecki Szpital Kliniczny w Poznaniu; Oddzia? Onkologii Klinicznej i Doswiadczalnej Poznan
Poland Narodowy Instytut Onkologii im. M. Sklodowskiej-Curie; Oddzial Badan Wczesnych Faz Warszawa
Spain Vall d?Hebron Institute of Oncology (VHIO), Barcelona Barcelona
Spain START Madrid-FJD, Hospital Fundacion Jimenez Diaz Madrid
Spain Hospital Clínico Universitario de Valencia; Servicio de Oncología Valencia
Taiwan National Cheng Kung University Hospital; Oncology Tainan
Taiwan Taipei Veterans General Hospital; Department of Oncology Taipei City
Taiwan National Taiwan University Hospital; Oncology Zhongzheng Dist.
United Kingdom Addenbrookes Hospital Cambridge
United Kingdom Velindre Cancer Centre Cardiff
United Kingdom Imperial College Healthcare NHS Trust London
United Kingdom Royal Free Hospital; Dept of Oncology London
United Kingdom Royal Marsden Hospital; Dept of Med-Onc; . London
United Kingdom Sarah Cannon Research Institute London
United Kingdom The Christie NHS Foundation Trust Manchester
United Kingdom Royal Marsden Hospital; Institute of Cancer Research Sutton
United States University of Colorado Cancer Center Aurora Colorado
United States Mary Bird Perkins Cancer Ctr Baton Rouge Louisiana
United States UAB Comprehensive Cancer Center; Clinical Studies Unit Birmingham Alabama
United States Massachusetts General Hospital Boston Massachusetts
United States New York Cancer & Blood Specialists Bronx New York
United States New York Cancer & Blood Specialists - Bronx Bronx New York
United States City of Hope Comprehensive Cancer Center Duarte California
United States Duke University Medical Center Durham North Carolina
United States cCare Encinitas California
United States Mayo Clinic in Florida; Department of Hematology Jacksonville Florida
United States Lumi Research Kingwood Texas
United States Cedars-Sinai Medical Center Los Angeles California
United States UCLA Los Angeles California
United States USC Norris Cancer Center Los Angeles California
United States Sarah Cannon Research Institute / Tennessee Oncology Nashville Tennessee
United States Vanderbilt University Medical Center Nashville Tennessee
United States Yale Cancer Center New Haven Connecticut
United States New York Cancer & Blood Specialists - New Hyde Park New Hyde Park New York
United States New York Cancer and Blood Specialists-Central Park Hematology & Oncology New York New York
United States Eastern Ct Hema/Onco Assoc; Dept of Oncology Norwich Connecticut
United States Stanford Cancer Center Palo Alto California
United States Mayo Clinic Arizona Phoenix Arizona
United States UPMC - Hillman Cancer Center Pittsburgh Pennsylvania
United States Mayo Clinic Rochester Rochester Minnesota
United States Hematology Oncology Salem Salem Oregon
United States Swedish Cancer Inst. Seattle Washington
United States Moffitt Cancer Center Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Denmark,  Germany,  Italy,  Korea, Republic of,  Poland,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Objective Response Rate Defined as the proportion of patients with a complete response or partial response, as determined by the investigator according to RECIST v1.1 Approximately 60 months
Secondary Duration of Response Defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 Approximately 60 months
Secondary Disease Control Rate Defined as the proportion of patients with stable disease, or a complete or partial response, as determined by the investigator according to RECIST v1.1 Approximately 60 months
Secondary Percentage of Participants with Adverse Events (AEs) Percentage of participants with adverse events. Approximately 60 months
Secondary Plasma Concentrations of Divarasib Plasma concentration of divarasib for divarasib + cetuximab + FOLFOX, divarasib + cetuximab, and divarasib + cetuximab+ FOLFIRI treatment arms. At pre-defined intervals from first administration of study drug up to approximately 60 months
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