Research & Trial Information
Protocol#: NRG – GI004/SWOG – S1610
Cancer Type: Colorectal Metastatic
- 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).
- 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 FFPE block containing tumor tissue; or • At least 9 unstained slides containing tumor sections
- Documentation by PET/CT scan, CT scan, or MRI that the patient has untreated measurable metastatic disease.
- No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass.
- No patients with CNS metastases are excluded.
- No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm), no history of intracranial hemorrhage or spinal cord hemorrhage, no ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted and no neurosurgical resection or brain biopsy within 28 days prior to randomization.
- Uncontrolled high blood pressure, no Serious or non-healing wound, skin ulcer, or bone fracture and no history of TIA, CVA, GI perforation or arterial thrombotic event within 6 months prior to randomization or symptomatic peripheral ischemia.
- 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.
- No prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization.
- Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents. Patients who have received prior treatment with anti-CTLA-4 may be enrolled provided the following requirements are met:
Minimum of 12 weeks from the first dose of anti-CTLA-4 and > 6 weeks from the last dose to randomization
No history of severe immune-related adverse effects (CTCAE Grade 3 and 4) from anti-CTLA-4.
- 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.
- No treatment with systemic immunostimulatory medications.
- No treatment with systemic immunosuppressive medications.
- No patients taking bisphosphonate therapy for symptomatic hypercalcemia.
- No treatment with any other investigational agent within 4 weeks prior to randomization.
- No History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
- No Severe infections within 28 days prior to randomization, including but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia.
- Signs or symptoms of infection within 14 days prior to randomization.