Clinical Trial Information

Protocol – NRG – GI004

SCHEMA NRG GI004

Please Note: Below is a brief description of eligibility, please contact GHCI to discuss full eligibility requirements.

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. 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.
5. Documentation by PET/CT scan, CT scan, or MRI that the patient has measurable metastatic disease per RECIST 1.1.
6. No immediate need for surgical intervention for the primary tumor or palliative diversion/bypass.

Ineligibility Criteria:

1. Patients with CNS metastases are excluded.
2. Patients with asymptomatic treated CNS metastases.
3. 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.
4. 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.
5. 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.
6. Prior treatment with oxaliplatin chemotherapy within 6 months prior to randomization.
7. 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.
8. Treatment with systemic immunostimulatory medications (including, but not limited to interferon [IFN]-α or interleukin [IL]-2 within 42 days prior to randomization.
9. 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.
10. Patients taking bisphosphonate therapy for symptomatic hypercalcemia. Use of bisphosphonate therapy for other reasons (e.g., bone metastasis or osteoporosis) is allowed.

Clinical Trial Information

Protocol: SWOG – S1922

SCHEMA S1922

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss eligibility requirements.

Eligibility:

1. Patients must have histologically or cytologically confirmed small bowel adenocarcinoma. Ampullary adenocarcinomas are not eligible. Patients must have metastatic disease or locally advanced unresectable disease.
2. Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to registration. Patients must be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to registration.
3. Patients must have measurable or non-measurable disease. All scans needed for assessment of measurable disease must be performed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration.
4. Patients must have progressed on prior therapy with a fluoropyrimidine and/or oxaliplatin, given either for metastatic / locally advanced disease or as adjuvant therapy completed within the previous 12 months.
5. Patients must not have received prior treatment with irinotecan, taxane, or ramucirumab for small bowel adenocarcinoma.
6. Patients must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to registration and all toxicity must be resolved to Grade 1 (with the exception of Grade 2 neuropathy) prior to registration. In CTCAE version 5.0 Grade 2 sensory neuropathy is defined as “moderate symptoms; limiting instrumental activities of daily living (ADLs)”
7. Patients must not have had major surgery within 28 days prior to registration, or minor surgery within 7 days prior to registration, and must not be planned for elective major surgery to be performed during protocol treatment.
8. Patients must not be currently enrolled in or have discontinued within the last 28 days a clinical trial involving an investigational product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients participating in surveys or observational studies are eligible to participate in this study.
9. Patients must not be receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents.
10. Patients must be ≥ 18 years of age.
11. Patients must have a complete medical history and physical exam within 28 days prior to registration.
12. Patients must have a Zubrod Performance Status of 0 or 1.
13. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
14. Patient tumors must not have known deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H).

Clinical Trial Information

PROTOCOL: SWOG-S1613

SCHEMA S1613

Please note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is metastatic or locally advanced and unresectable.
2. All patients must have molecular testing performed in a CLIA certified lab which includes KRAS and NRAS gene and exon 15 of BRAF gene (BRAF V600E mutation). Patients with any known activating mutation in exon 2 [codons 12 and 13], exon 3 [codons 59 and 61] and exon 4 [codons 117 and 146]) of KRAS/NRAS genes and in exon 15 (BRAFV600E mutation) of BRAF gene are not eligible.
3. Patients must not have been treated with any of the following prior to Step 1 Initial Registration:
   1. • Cetuximab, or any other monoclonal antibody against EGFR or inhibitor of
      EGFR.
      • HER-2 targeting for treatment of colorectal cancer. Patients who have received
      prior trastuzumab or pertuzumab for other indications such as prior history of
      adjuvant or neoadjuvant breast cancer treatment prior to the development of
      advanced colorectal cancer are eligible.
4. Patients must not have had history of severe toxicity and intolerance to or hypersensitivity to irinotecan or any other study drug. Patients must not have had a severe infusion-related reaction during any prior therapy with pertuzumab or trastuzumab.
5. Patients must have HER-2 amplification as determined by central testing (3+ or 2+by immunohistochemistry and HER-2 gene amplification by in situ hybridization with a ratio of HER-2 gene signals to centromere 17 signals ≥ 2.0).
6. Patients must have measurable disease that is metastatic or locally advanced and unresectable.
7. Patients must have had at least one prior regimen of systemic chemotherapy for metastatic or locally advanced, unresectable disease. Patients must have progressed following the most recent therapy. Prior treatment with irinotecan is allowed. For patients that received adjuvant chemotherapy: Prior treatment for metastatic disease is not required for patient who experienced disease recurrence
   during or within 6 months of completion of adjuvant chemotherapy. If the patient received one line of adjuvant treatment and had disease recurrence after 6 months of completing chemotherapy, patients will only be eligible after failing one additional line of chemotherapy used to treat the metastatic or locally advanced, unresectable disease. Patients who have received ≥3 lines of systemic
   chemotherapy for metastatic or locally advanced, unresectable disease are not eligible.
8. Patients must have a Zubrod Performance Status of 0 or 1.
9. Patients must be ≥ 18 years of age.

Clinical Trial Information

PROTOCOL: Alliance-A021703

SCHEMA A021703

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Histologically confirmed locally advanced/metastatic colorectal adenocarcinoma with no planned metastasectomy.
2. No dMMR or MSI-H disease.
3. – Measurable disease.
4. No prior systemic treatment for metastatic disease.
5. Prior neoadjuvant or adjuvant chemotherapy/radiation allowed if completed > 12 months prior to colorectal cancer recurrence.
6. Prior rectal chemoradiation permitted if radiotherapy was to ≤ 25% of bone marrow and completed ≥ 4 weeks prior to registration.
7. No continuous daily vitamin D ≥ 2,000 IU/day for the 12 months prior to registration.
8. Major surgery/open biopsy completed ≥ 4 weeks and/or minor surgery/core biopsy completed ≥ 1 weeks prior to registration.
9. Age ≥ 18 years; ECOG PS: 0-1.
10. No resectable metastatic disease for which potentially curative metastasectomy is planned.
11. No “currently active” second malignancy other than non-melanoma skin cancers or cervical carcinoma in situ.
12. Concurrent use of calcium, vitamin D, thiazide diuretics, oral corticosteroids, or other anti-cancer therapy not permitted

Clinical Trial Information

PROTOCOL: Alliance-A021502

SCHEMA A021502

Please Note: Below is a brief description of eligibility, please contact GHCI Research Department to discuss full eligibility requirements.

ELIGIBILITY:

1. Histologically proven stage III colon adenocarcinoma.
2. Presence of deficient MMR (dMMR) via IHC.
3. Completely resected tumors.
4. Entire tumor in colon.
5. No evidence of residual involved lymph node disease or metastatic disease.
6. Patients known to have Lynch Syndrome are eligible.
7. No other planned concurrent investigational agents or other tumor directed therapy.
8. Age ≥ 18 years.
9. ECOG PS≤ 2.