A clinical trial to look at how well different targeted therapies work to treat metastatic colorectal cancer (mCRC)

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

  • Colorectal Cancer (CRC)
Trial Status:

Recruiting

This trial runs in
Countries
  • Canada
  • Italy
  • South Korea
  • Spain
  • United Kingdom
  • United States
Trial Identifier:

NCT04929223 WO42758

      Show trial locations

      The source of the below information is the publicly available website ClinicalTrials.gov. It has been summarised and edited into simpler language.

      The below information is taken directly from the publicly available website ClinicalTrials.gov within a week of any updates, and has not been edited.

      Results Disclaimer

      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.

      Hoffmann-La Roche Sponsor
      Phase 1 Phase
      NCT04929223 , WO42758 Trial Identifier
      All Gender
      ≥18 Years Age
      No Healthy Volunteers

      How does the INTRINSIC clinical trial work?

      This clinical trial is recruiting people who have metastatic colorectal cancer (mCRC), which is colorectal cancer that has spread to other parts of the body outside of the colorectal region. This clinical trial will test new drugs that target specific changes or genetic alterations in an individual’s tumour.

      Depending on the genetic features of your mCRC, you will join one of four cohorts, and will receive one of five treatment combinations: 

      • Cohort 1: atezolizumab plus tiragolumab plus bevacizumab, OR atezolizumab plus tiragolumab;
      • Cohort 2: SY-5609 plus atezolizumab (participants in the United States only);
      • Cohort 3: inavolisib plus cetuximab;
      • Cohort 4: inavolisib plus bevacizumab.

      The purpose of the current version of the clinical trial is to test the safety of these different targeted therapies and to understand how your body responds to these treatments. As the trial progresses, the safety and effectiveness of other new treatment options may be tested in individuals with mCRC with different changes or genetic alterations. Your doctor will always speak to you before any changes to your treatment occur.

       

      How do I take part in the INTRINSIC clinical trial?

      To be able to take part in this clinical trial, you must have been diagnosed with mCRC that has certain genetic features, and be at least 18 years old.

      You must not have received anti-cancer treatment within two weeks of starting the clinical trial, or another study treatment within 28 days of starting the clinical trial. If you are pregnant or breastfeeding, or intending to become pregnant during the clinical trial, you will not be able to take part. If you have certain other medical conditions or are taking certain treatments, you may not be able to take part in this clinical trial. There are other specific criteria that you may need to meet for each treatment in this clinical trial. Your doctor will be able to explain these to you.

      If you think this clinical trial may be suitable for you and would like to take part, please talk to your doctor. If your doctor thinks that you might be able to take part in this clinical trial, they may refer you to the closest clinical trial doctor. They will give you all the information you need to make your decision about whether or not to take part in the clinical trial. You can also find the clinical trial locations on this page.

      You will have some further tests to make sure you will be able to take the treatments given in this clinical trial. Some of these tests or procedures may be part of your regular medical care. They may be done even if you do not take part in the clinical trial. If you have had some of the tests recently, they may not need to be done again.

      Before starting the clinical trial, you will be told about any risks and benefits of taking part in the trial. You will also be told what other treatments are available so that you may decide if you still want to take part. While taking part in the clinical trial, both men and women (if you are not currently pregnant but can become pregnant) will need to either not have heterosexual intercourse or use contraceptive methods for safety reasons. Your doctor will discuss the details with you.

       

      What treatment will I be given if I join the INTRINSIC clinical trial?

      Everyone who joins this clinical trial will enter one of four trial cohorts, based on the genetic features of their mCRC.

      • Cohort 1: If you have ‘microsatellite instability-high’ (MSI-H) mCRC, which means that a lot of instability has been detected in your mCRC (due to defects in the proteins responsible for repairing DNA), you 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 the vein) once every three weeks
        • OR atezolizumab plus tiragolumab, both given as an infusion once every three weeks
      • Cohort 2 (participants in the United States only): If your mCRC has specific genetic alterations in the BRAF gene, you will be given SY-5609 as a pill once every day for seven days, followed by seven days off, as well as atezolizumab as an infusion once every four weeks
      • Cohort 3: If your mCRC has genetic alterations in the PIK3CA gene, you will be given inavolisib as a pill once every day, as well as cetuximab as an infusion once every week
      • Cohort 4: If your mCRC has genetic alterations in the PIK3CA and RAS genes, you will be given inavolisib as a pill once every day, as well as bevacizumab as an infusion once every three weeks.

       

      How often will I be seen in follow-up appointments and for how long?

      You will be given the clinical trial treatment for as long as it can help you. You are free to stop the clinical trial treatment at any time. While being given treatment, you will still be seen regularly by the clinical trial doctor. The number of visits you will have will depend on the treatment group you are in. These hospital visits will include checks such as a tumour assessment scan to see how you are responding to the treatment and checks for any side effects that you may be having. The tumour assessment scans will occur every six weeks for the first 48 weeks of the study and then every 12 weeks after that. After you stop treatment, you will still have follow-up appointments with the clinical trial doctor for as long as you agree to this. 

      What happens if I am unable to take part in this clinical trial?

      If this clinical trial is not suitable for you, you will not be able to take part. Your doctor may suggest other clinical trials that you may be able to take part in or other treatments that you can be given. You will not lose access to any of your regular care.

      For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow this link to ClinicalTrials.gov: https://clinicaltrials.gov/ct2/show/NCT04929223

      Trial identifier: NCT04929223

      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.

      Hoffmann-La Roche Sponsor
      Phase 1 Phase
      NCT04929223 , WO42758 Trial Identifier
      Inavolisib, Bevacizumab, Cetuximab, Atezolizumab, Tiragolumab, SY-5609, GDC-6036, FOLFOX Treatments
      Metastatic Colorectal Cancer Condition
      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)

      Eligibility Criteria

      All Gender
      ≥18 Years Age
      No Healthy Volunteers
      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
      • 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
      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
      • 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

      Clinical Research Explained

      Information about what clinical trials and observational studies are. Understand why you might want to take part in clinical research and why diversity in clinical research is important.

      Find out now