Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer
Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Recurrent Colon Cancer
About this trial
This is an interventional treatment trial for Mucinous Adenocarcinoma of the Colon
Eligibility Criteria
Inclusion Criteria: Stage IV colorectal adenocarcinoma, excluding brain metastases Histological confirmation of colorectal adenocarcinoma Previously untreated patients Previously treated patients For the Phase I trial, no limitations For the Phase II trial, previous treated limited to adjuvant radiation and/or chemotherapy which is completed at least 12 months before documentation of metastatic disease; patients may not have received chemotherapy for metastatic disease For the Phase I trial, patients may have measurable disease or unmeasurable disease; for the Phase II trial, patients must have measurable disease in at least two dimensions on x-rays, CT scan or MRI Expected survival of at least 16 weeks Performance status of >= 70% (Karnofsky) WBC >= 3000 uL Platelet count >= 100,000/uL Bilirubin =< 2 x ULN Creatinine =< 2 x ULN Not pregnant and not lactating; women of child bearing age must have negative pregnancy test (beta-hcg) No allergies to interferon-gamma or E.coli derived products No serious medical intercurrent medical illnesses, including Class III or IV cardiovascular disease; patient may not be dependent on immunosuppressive drugs including corticosteroids, and may not receive these drugs for the entire duration of the study No diarrhea, and with adequate oral intake Patients of child-bearing age and potential must agree to use adequate birth control other than oral contraceptives for the entire duration of the study No previous or concurrent malignancy except inactive nonmelanoma skin cancer, in situ carcinoma of the cervix, grade 1 bladder cancer, or other cancers if the patient has been disease free for >= 5 years Patients must be oriented and rational, and aware of the investigational nature of the study
Sites / Locations
- Mount Sinai Medical Center
Arms of the Study
Arm 1
Experimental
Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G
Phase I: Patients receive 5-FU IV over 24 hours on day 1; phenylbutyrate IV over 120 hours and oral indomethacin daily on days 2-6; and interferon gamma subcutaneously on days 2, 4, and 6. Courses repeat weekly in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 5-FU until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which less than 2 of 6 patients experience dose-limiting toxicity (DLT). Phase II: Patients receive 5-FU, phenylbutyrate, indomethacin, and interferon gamma as in phase I at the MTD.