Clinical Trial Information
Protocol – NRG – GI004
Please Note: Below is a brief description of eligibility, please contact GHCI to discuss full eligibility requirements.
- Age ≥ 18 years.
- ECOG Performance Status of 0, 1 or 2.
- Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer.
- Tumor determined to be mismatch-repair deficient (dMMR) by CLIA-certified immunohistochemical (IHC) assay with a panel of all four IHC markers, including MLH1, MSH2, PMS2, and MSH6. Alternatively, MSI-H diagnosed by polymerase chain reaction (PCR)-based assessment of microsatellite alterations (either Bethesda markers or Pentaplex panel) or by next-generation sequencing (NGS) are eligible.
- Documentation by PET/CT scan, CT scan, or MRI that the patient has measurable metastatic disease per RECIST 1.1.
- No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass.
- Patients with CNS metastases are excluded.
- Patients with asymptomatic treated CNS metastases.
- Any of the following cardiac conditions:
• Documented NYHA Class III or IV congestive heart failure
• Myocardial infarction within 6 months prior to randomization
• Unstable angina within 6 months prior to randomization
• Symptomatic arrhythmia.
- History of TIA, CVA, GI perforation or arterial thrombotic event within 6 months prior to randomization, symptomatic peripheral ischemia, or other medical condition in the opinion of the treating oncologist that makes the risk of cardiovascular or bleeding complications with bevacizumab use unacceptably high.
- Other malignancies are excluded unless the patient has completed therapy for the malignancy ≥ 12 months prior to randomization and is considered disease-free. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: in situ carcinomas or basal cell and squamous cell carcinoma of the skin.
- Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization.
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (other than alopecia) due to agents administered more than 4 weeks earlier are excluded; however, the following therapies are allowed:
− Hormone-replacement therapy or oral contraception
− Herbal therapy > 7 days prior to randomization (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to randomization)
− Palliative radiotherapy for bone metastases >14 days prior to randomization.
- Treatment with systemic immunostimulatory medications (including, but not limited to interferon [IFN]-α or interleukin [IL]-2 within 42 days prior to randomization.
- Treatment with systemic immunosuppressive medications (including, but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 14 days prior to randomization; however,
• Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea; or chronic daily treatment with corticosteroids with a dose of ≤ 10 mg/day methylprednisolone equivalent) may be enrolled.
• The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.
- Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.