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)

Study Identifier:
WO42758
CT.gov Identifier:
NCT04929223
EudraCT Identifier:
2021-001207-33
EU Trial (CTIS) Number:
2023-505163-37-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

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.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bowel (Colorectal)
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: Inavolisib + Cetuximab
    • Read More
  • Drug: Cohort 1: If a participants’ mCRC has genetic alterations in the KRAS G12C gene, and they have not previously had chemotherapy that contained oxaliplatin, they will be given: GDC-6036 as a pill once every day, as well as cetuximab plus FOLFOX, each given as an infusion once every two weeks Cohort 2: If a participants’ mCRC has genetic alterations in the KRAS G12C gene and their cancer was not effectively controlled by, they did not tolerate, or they refused to be given oxaliplatin-containing chemotherapy, they will be given GDC-6036 as a pill once every day, as well as cetuximab as an infusion once every two weeks Cohort 3: If participants have ‘microsatellite instability-high’ (MSI-H) mCRC, which means that a lot of instability has been detected in their mCRC (due to defects in the proteins responsible for repairing DNA), they will be split into two groups randomly (like flipping a coin) and given either: Atezolizumab plus tiragolumab plus bevacizumab, each given as an infusion (into a vein) once every three weeks OR atezolizumab plus tiragolumab, both given as an infusion once every three weeks Cohort 4 (participants in the United States only): If a participants’ mCRC has specific genetic alterations in the BRAF gene, they will be given SY-5609 as a pill (to be swallowed) once every day for seven days, followed by seven days off, as well as atezolizumab as an infusion once every four weeks Cohort 5: If a participants’ mCRC has genetic alterations in the PIK3CA gene, they will be given inavolisib as a pill once every day, as well as cetuximab as an infusion once every week Cohort 6: If a participants’ mCRC has genetic alterations in the PIK3CA and RAS genes, they will be given inavolisib as a pill once every day, as well as bevacizumab as an infusion once every three weeks.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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
    • Inclusion criteria for biomarker suitability analysis
    • For biomarker suitability analysis, patients will need to meet all of the following criteria:
    • Signing of the informed consent form for the NGS biomarker suitability test.
    • Age ≥ 18 years at the time of signing the informed consent form.
    • Full report of previous test results (if available) not meeting the screening criteria.
    • Inclusion criteria for screening
    • To enter the study, patients will need to meet all of the following criteria:
    • For patients with positive biomarker status: signing of the NGS biomarker suitability test informed consent form and signing of the treatment arm specific informed consent form.
    • Biomarker suitability (as defined by specific treatment arms) determined by a validated test at a CAP/CLIA certified diagnostic laboratory or similar accreditation based on:
    • A result obtained in a previous test and the availability of a full report of the test results
    • OR
    • FoundationOne Liquid CDx blood-based biomarker suitability test result generated before or during screening or upon re-enrollment after treatment interruption prior to initiation of new cancer therapy.
    • Age ≥ 18 years at the time of signing the informed consent form.
    • Eastern Cooperative Oncology Group performance status of ≤ 1
    • Life expectancy ≥ 3 months as determined by the investigator.
    • Adenocarcinoma originating in the colon or rectum confirmed by histological examination.
    • Metastatic disease (American Joint Committee on Cancer system stage IV, version 7).
    • Prior therapies for metastatic disease: see relevant treatment arm specific appendix; the criteria regarding previous therapies may in fact vary from one treatment arm to another.
    • Ability to comply with the study protocol according to the opinion of the investigator.
    • Measurable disease (at least one target lesion) according to RECIST v1.1 criteria.
    • Previously irradiated lesions can only be considered measurable disease if disease progression at that site has been unequivocally documented since radiation therapy.
    • Availability of a preserved tissue sample for exploratory biomarker research.
    • In the absence of this sample, the patient may be deemed suitable after comparison with the Medical Monitor.
    • Adequate hematologic and organ function within 14 days prior to initiation of study treatment, as defined below:
    • Absolute neutrophil count ≥ 1500/μl without the support of granulocyte colony-stimulating factors.
    • White blood cell count (WBC) ≥ 2.5 x 10 9 /l (2500/ml).
    • Lymphocyte count ≥ 0.5 x 10 9 /l (500/ml).
    • Platelet count ≥ 100,000/μl.
    • Hemoglobin ≥ 9 g/dl.
    • To meet this criterion, patients must not have had any transfusions in the 2 weeks prior to screening.
    • Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) (≤ 3 times the ULN in Gilbert's disease).
    • Serum albumin ≥ 2.8 g/dl or 28 g/l.
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 times the ULN with the following exception:
    • Patients with documented liver metastases may have AST and/or ALT levels ≤ 5.0 times the ULN.
    • Alkaline phosphatase (ALP) ≤ 2.5 times the ULN with the following exception:
    • Patients with documented bone or liver metastases: ALP ≤ 5.0 times the ULN.
    • Creatinine clearance ³ 50 ml/min (calculated with the Cockcroft-Gault formula) or creatinine ≤ 1.5 times the ULN.
    • For patients not receiving anticoagulant treatment: international normalized ratio (INR) ≤ 1.5 times the ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 times the ULN.
    • In addition to the above inclusion criteria, patients must meet all arm-specific inclusion criteria to be enrolled in a study treatment arm. These criteria may be more stringent, as specified in the sections below relating to individual treatment arms.
    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
    • In addition to the above exclusion criteria, patients will not need to meet any of the arm-specific exclusion criteria to be enrolled in a study treatment arm. These criteria may be more stringent, as specified in the sections below relating to individual treatment arms.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruiting
    Condition(s) Treated at Site
    Bowel (Colorectal)