Study of Gamma Interfereon in Metastatic Colorectal Carcinoma

Phase II Study of Gamma Interferon (IFN-γ) Added to Bolus + Infusional 5-Fluorouracil (5-FU) and Leucovorin (LV) +/- Bevacizumab (BV) in Metastatic Colorectal Carcinoma

The purpose of this study is to evalute the response and toxicity of metastatic colorectal cancer patients to the regimen of gamma interferon added to bolus and infusional 5-fluorouracil and leucovorin (GFL) with or without bevacizumab.

Inclusion Criteria:

• Metastatic colorectal cancer, histologically or cytologically confirmed
• Age 18 or greater
• Adequate hematologic function (ANC > 1500, hemoglobin > 10 g/dl, platelet count > 100,000)
• Adequate hepatic parameters (bilirubin < 2.0, Alk. Phos < 5 times normal, ALT < 5 times normal)
• Adequate renal function (creatinine < 2.0)
• Performance status ECOG 0-2
• 0-2 prior lines of chemotherapy for metastatic colorectal cancer are allowed. Prior 5-FU/LV or capecitabine allowed either in the adjuvant setting, or in the metastatic setting or both.
• Absence of other serious concurrent medical illnesses
• Evaluable or measurable disease for phase I; measurable disease only for phase II

Exclusion Criteria:

• Histologies other than adenocarcinoma
• Previous grade 4 toxicity to 5-FU +/- LV or capecitabine
• Uncontrolled brain metastases
• Chronic diarrhea (greater than five bowel movements per day)
• Previous chemotherapy or radiation therapy less than 4 weeks prior to study day 1 (less than 6 weeks for chemotherapy with Mitomycin or nitrosoureas)
• Major surgery within 2 weeks before study entry
• Known allergic sensitivity to leucovorin
• Prior exposure to IFN-γ
• Previous hematopoietic growth factor (e.g. epoetin alfa or darbepoietin less than 2 weeks prior to study day 1)
• Pregnancy or breast feeding. Women of child-bearing potential must have a negative pregnancy test before the first dose.
• Other co-existing malignancies or malignancies diagnosed within the last 5 years, with the exception of basal cell carcinoma or cervical cancer in situ
• Inability to provide written and informed consent
• Uncontrolled hypertension
• History of deep venous thrombosis or CVA
• Prior exposure to bevacizumab
• Proteinuria > 500 mg/24 hr