Research & Trial Information

SCHEMA NRG GI004

Protocol#: NRG – GI004/SWOG-S1610

Cancer Type: Colorectal Metastatic

Patient Eligibility:

1. Age 18 years.
2. ECOG Performance Status of 0, 1 or 2.
3. Diagnosis of metastatic adenocarcinoma of colon or rectum without previous chemotherapy or any other systemic therapy for metastatic colorectal cancer.
4. 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. Note: MSI-H diagnosed by 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.
5. 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

    

6. • At least 9 unstained slides containing tumor sections
7. Documentation by PET/CT scan, CT scan, or MRI that the patient has untreated measurable metastatic disease.
8. No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass.
9. Patients with CNS metastases are excluded, with the following exceptions:
   • • Patients with asymptomatic untreated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following:
   •  Evaluable or measurable disease outside the CNS 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.

      No neurosurgical resection or brain biopsy within 28 days prior to randomization.

10. Patients with asymptomatic treated CNS metastases may be enrolled, provided all eligibility criteria are met, as well as the following: Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study

     No stereotactic radiation or whole-brain radiation within 28 days prior to randomization

     Screening CNS radiographic study within  28 days from completion of radiotherapy and within  14 days from discontinuation of corticosteroids.

11. 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.
12.  No prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization.
13. No 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.

14.    No patients who have had chemotherapy or radiotherapy within 4 weeks.
15.   No treatment with systemic immunostimulatory medications.
16.  No treatment with systemic immunosuppressive medications. 

Research & Trial Information

SCHEMA A021502

Protocol#: Alliance – A021502

Cancer Type: Colorectal

Patient Eligibility:

1. Histologically proven stage III colon adenocarcinoma (any T [Tx, T1, T2, T3, or T4], N1-2M0; includes N1C). Tumors must be deemed to originate in the colon including tumors that extend into/involve the small bowel (e.g. those at the ileocecal valve). DNA Mismatch Repair (MMR) Status: Presence of deficient (d) DNA mismatch repair (dMMR). MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR. Patients with testing that did not show dMMR (loss of MMR protein) are not eligible to participate. Patients whose tumors show MSI-H by PCR-based assay are not eligible to participate unless they also have MMR testing by IHC and are found to have dMMR (i.e. loss of one or more MMR proteins). Patients who are known to have Lynch Syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) are eligible to participate.
2. Tumors must have been completely resected. Entire tumor must be in the colon (rectal involvement is an exclusion). No evidence of residual involved lymph node disease or metastatic disease at the time of registration based on clinician assessment of imaging.
3. No prior medical therapy (chemotherapy, immunotherapy, biologic or targeted therapy) or radiation therapy for the current colon cancer except for one cycle of mFOLFOX6.
4. No active known autoimmune disease, including colitis, inflammatory bowel disease (i.e. ulcerative colitis or Crohn’s disease), rheumatoid arthritis, panhypopituitarism, adrenal insufficiency.
5. No other planned concurrent investigational agents or other tumor directed therapy (chemotherapy, radiation) while on study and no systemic daily treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications.