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

NCT04929223
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
542
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Lead sponsor
Hoffmann-La Roche
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Start date
2021-10-22
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Number of sites
84
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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.
clinicaltrials.gov
Short title
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
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Official title
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)
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2030-08-31
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First posted
2021-06-18
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Registry last updated
2026-08-17
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Primary completion date
2030-08-31
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Start date
2021-10-22
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Participants
542
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Participant count basis
Estimated
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Planned participants
542
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Protocol amendments
9
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Number of sites
84
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Hoffmann-La Roche
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Source registry
ClinicalTrials.gov
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Registry ID
NCT04929223
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ClinicalTrials.gov ID
NCT04929223
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Objective Response Rate

    Timeframe: Approximately 84 months

    Defined as the proportion of participants with a complete response or partial response, as determined by the investigator according to RECIST v1.1

  1. Duration of Response

    Timeframe: Approximately 84 months

    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

  2. Disease Control Rate

    Timeframe: Approximately 84 months

    Defined as the proportion of participants with stable disease, or a complete or partial response, as determined by the investigator according to RECIST v1.1

  3. Percentage of Participants with Adverse Events (AEs)

    Timeframe: Approximately 84 months

    Percentage of participants with adverse events.

  4. Plasma Concentrations of Divarasib

    Timeframe: At pre-defined intervals from first administration of study drug up to approximately 84 months

    Plasma concentration of divarasib for divarasib + cetuximab + FOLFOX, divarasib + cetuximab, and divarasib + cetuximab+ FOLFIRI, Divarasib + Bevacizumab + FOLFOX, Divarasib + Bevacizumab + FOLFIRI treatment arms.

  5. Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFOX

    Timeframe: Approximately 84 months

    Recommended dose of divarasib in combination with bevacizumab and FOLFOX based on the totality of safety, efficacy and PK data.

  6. Recommended Dose of Divarasib in Combination with Bevacizumab and FOLFIRI

    Timeframe: Approximately 84 months

    Recommended dose of divarasib in combination with bevacizumab and FOLFIRI based on the totality of safety, efficacy and PK data.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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
Sources for eligibility
clinicaltrials.gov

  • UAB Comprehensive Cancer CenterBirmingham, United StatesWithdrawn
  • Mayo Clinic ArizonaPhoenix, United StatesRecruiting
  • City of Hope Comprehensive Cancer CenterDuarte, United StatesRecruiting
  • cCareEncinitas, United StatesWithdrawn
  • USC Norris Cancer CenterLos Angeles, United StatesCompleted
  • Cedars-Sinai Medical CenterLos Angeles, United StatesRecruiting
  • UCLALos Angeles, United StatesRecruiting
  • Hoag Memorial Hospital PresbyterianNewport Beach, United StatesWithdrawn
  • Stanford Cancer CenterStanford, United StatesCompleted
  • University of Colorado Cancer CenterAurora, United StatesRecruiting
  • Rocky Mountain Cancer Centers, LLPLone Tree, United StatesRecruiting
  • Yale Cancer CenterNew Haven, United StatesRecruiting
  • Eastern Ct Hema/Onco AssocNorwich, United StatesWithdrawn
  • Mayo Clinic in FloridaJacksonville, United StatesRecruiting
  • Moffitt Cancer CenterTampa, United StatesRecruiting
  • Illinois Cancer SpecialistsArlington Heights, United StatesRecruiting
  • Mary Bird Perkins Cancer CtrBaton Rouge, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesCompleted
  • Karmanos Cancer InstituteDetroit, United StatesWithdrawn
  • Mayo Clinic RochesterRochester, United StatesRecruiting
  • New York Cancer & Blood Specialists - New Hyde ParkNew Hyde Park, United StatesRecruiting
  • New York Cancer and Blood Specialists-Central Park Hematology & OncologyNew York, United StatesRecruiting
  • New York Cancer & Blood SpecialistsPort Jefferson Station, United StatesRecruiting
  • New York Cancer & Blood Specialists - BronxThe Bronx, United StatesRecruiting
  • Duke University Medical CenterDurham, United StatesCompleted

And 59 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-505163-37-00
  • 2021-001207-33
Sources for references
clinicaltrials.gov

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