Protocol Summary

Protocol No.: OCR17028

Sponsor Protocol No.: NRG-GI004; S1610

Protocol Title: Combination Chemotherapy, Bevacizumab, and/or Atezolizumab in Treating Patients With Deficient DNA Mismatch Repair Metastatic Colorectal Cancer

Principal Investigator: George, Thomas

Objective: This randomized phase III trial studies how well combination chemotherapy, bevacizumab, and/or atezolizumab work in treating patients with deficient DNA mismatch repair colorectal cancer that has spread to other places in the body. Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab and atezolizumab, may interfere with the ability of tumor cells to grow and spread. Giving combination chemotherapy, bevacizumab, and atezolizumab may work better in treating patients with colorectal cancer.

Description: Patients are randomized to 1 of 3 arms. ARM I: Patients receive bevacizumab intravenously (IV) over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 of courses 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on days 1 and 2. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 2 weeks for up to 48 courses in the absence of disease progression or unacceptable toxicity. ARM III: Patients receive atezolizumab IV over 30-60 minutes on day 1. Courses with repeat every 2 weeks for up to 48 courses in the absence of disease progression or unacceptable toxicity. Patients also received bevacizumab IV over 30-90 minutes on day 1, oxaliplatin IV over 2 hours on day 1 courses 1-10, leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV over 46-48 hours on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 8 weeks for 18 months, and then every 12 weeks for up to 5 years.

Phase: Phase III

Age Group: Adult

Age: 18 Years - N/A

Gender: All

Scope: National

Treatment:
Arm I (bevacizumab, mFOLFOX6)
Patients receive bevacizumab on day 1, oxaliplatin on day 1 of courses 1-10, leucovorin calcium on day 1, and fluorouracil on days 1 and 2. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
Arm II (atezolizumab)
Patients receive atezolizumab on day 1. Treatment repeats every 2 weeks for up to 48 courses in the absence of disease progression or unacceptable toxicity.
Arm III (atezolizumab, bevacizumab, mFOLFOX6)
Patients receive atezolizumab on day 1. Courses with repeat every 2 weeks for up to 48 courses in the absence of disease progression or unacceptable toxicity. Patients also received bevacizumab on day 1, oxaliplatin on day 1 courses 1-10, leucovorin calcium on day 1, and fluorouracil on day 1. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.

Detailed Eligibility:
INCLUSION CRITERIA:
1. Ages 18 years old and older
2. The patient must have signed and dated an Institutional Review Board (IRB)-approved consent form that conforms to federal and institutional guidelines
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
4. Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer
5. Tumor determined to be mismatch-repair deficient (dMMR) by Clinical Laboratory Improvement Act (CLIA)-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6; Note: microsatellite instability high (MSI-H) diagnosed by microsatellite instability (MSI) testing (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) is not eligible unless dMMR is confirmed by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers including MLH1, MSH2, PMS2 and MSH6
6. An adequate amount of archived tumor tissue, either from primary colorectal cancer site or metastatic lesions, for central confirmation of dMMR status:
- Either whole or part of the formalin-fixed paraffin-embedded (FFPE) block containing tumor tissue; or
- At least 8 unstained slides containing tumor sections
7. Documentation by positron emission tomography(PET)/computed tomography (CT) scan, CT scan, or magnetic resonance imaging (MRI) that the patient has untreated measurable metastatic disease per RECIST 1.1
8. No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass
9. Obtained within 28 days prior randomization: absolute neutrophil count (ANC) must be >= 1500/mm^3
10. Obtained within 28 days prior randomization: platelet count must be >= 100,000/mm^3
11. Obtained within 28 days prior randomization: hemoglobin must be >= 8 g/dL
12. Obtained within 28 days prior randomization: total bilirubin must be = 1.5 x ULN to 3 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
13. Obtained within 28 days prior randomization: alkaline phosphatase must be =14. Obtained within 28 days prior randomization: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be =15. Obtained within 28 days prior randomization: serum creatinine == 30 mL/min
16. A urine sample tested for proteinuria by the dipstick method must indicate 0 -1+ protein; if dipstick reading is >= 2+, a 24-hour urine specimen must demonstrate 17. International normalized ratio of prothrombin time (INR) and prothrombin time (PT) must be =
** Contact study team for complete eligibility details.

Applicable Conditions:

  • Colon Cancer
  • Participation Institution:

  • UF Gainesville : Twanda Robinson
  • Contact:
    Twanda Robinson, RN
    Phone: +1 352-273-9489
    Email: twanda.robinson@medicine.ufl.edu

    More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT02997228