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

NCT04929223

Description:

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.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (Intrinsic)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: WO42758
  • NCT ID: NCT04929223

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
InavolisibInavolisib + Bevacizumab
BevacizumabInavolisib + Bevacizumab
CetuximabInavolisib + Cetuximab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Inavolisib + CetuximabExperimentalParticipants will receive 9 milligrams (mg) of inavolisib by mouth once daily (QD) on Days 8-28 of Cycle 1, then QD on Days 1-28 from Cycle 2 onwards (1 cycle=28 days). Participants will also receive cetuximab intravenous (IV) infusion 400 mg/m2 body surface area on Day 1 of Cycle 1. All subsequent weekly (QW) doses will be 250 mg/m2 each.
  • Inavolisib
  • Cetuximab
Inavolisib + BevacizumabExperimentalParticipants will receive 9 mg of inavolisib by mouth QD combined with bevacizumab 15 milligram/kilogram (mg/kg) IV once every three weeks (Q3W) on Day 1 of each cycle (1 cycle=21 days).
  • Inavolisib
  • Bevacizumab

Eligibility Criteria

        Inclusion Criteria

          -  Signed next-generation sequencing (NGS) Biomarker Eligibility 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)

          -  Availability of an archival tissue sample for exploratory biomarker research

          -  Adequate hematologic and organ function within 14 days prior to initiation of study
             treatment

        Exclusion Criteria

          -  Current participation or enrollment in another interventional clinical trial

          -  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

          -  For women of childbearing potential: Must have a negative serum pregnancy test result
             within 14 days prior to initiation of study treatment and agreement to remain
             abstinent or use contraceptive measures

          -  For men: agreement to remain abstinent or use contraceptive measures, and agreement to
             refrain from donating sperm

          -  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

          -  Known HIV infection

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:Approximately 24 months
Safety Issue:
Description:Defined as the proportion of patients with a complete response or partial response, as determined by the investigator according to RECIST v1.1

Secondary Outcome Measures

Measure:Duration of Response
Time Frame:Approximately 24 months
Safety Issue:
Description: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
Measure:Disease Control Rate
Time Frame:Approximately 24 months
Safety Issue:
Description: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
Measure:Percentage of Participants with Adverse Events (AEs)
Time Frame:Approximately 24 months
Safety Issue:
Description:Incidence, type, and severity of adverse events graded by the NCI CTCAE v5.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

August 6, 2021