RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interferon-gamma may interfere with the growth of tumor cells and slow the growth of the tumor. Combining more than one drug with interferon-gamma may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of giving fluorouracil together with phenylbutyrate, indomethacin, and interferon-gamma and to see how well it works in treating patients with stage IV colorectal cancer.

Condition	Treatment or Intervention	Phase
stage IV colon cancer Stage IV rectal cancer recurrent colon cancer recurrent rectal cancer adenocarcinoma of the colon adenocarcinoma of the rectum	Drug: fluorouracil  Drug: indomethacin  Drug: interferon gamma  Drug: phenylbutyrate  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: cytokine therapy  Procedure: drug modulation  Procedure: interferon therapy	Phase I Phase II

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of fluorouracil administered with phenylbutyrate, indomethacin, and interferon gamma in patients with advanced colorectal adenocarcinoma.
• Determine the toxic effects of this regimen in these patients.
• Determine the efficacy of this regimen in these patients.

OUTLINE: This is a dose-escalation study of fluorouracil (5-FU).

• 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. Patients are followed for survival.

PROJECTED ACCRUAL: A maximum of 24 patients will be accrued for the phase I portion of this study and approximately 46 patients will be accrued for the phase II portion of this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed stage IV colorectal adenocarcinoma
• Bidimensionally measurable disease on x-ray, CT scan, or MRI required for phase II patients
• No brain metastases

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 70-100%

Life expectancy:

• At least 16 weeks

Hematopoietic:

• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Bilirubin no greater than 2 times upper limit of normal (ULN)

Renal:

• Creatinine no greater than 2 times ULN

Cardiovascular:

• No New York Heart Association class III-IV heart disease

Nutritional:

• Adequate oral intake
• No diarrhea

Other:

• No other serious concurrent illness
• No dependence on immunosuppressive drugs, including corticosteroids
• No other malignancy within the past 5 years except:
• Inactive nonmelanoma skin cancer
• Carcinoma in situ of the cervix
• Grade I bladder cancer
• No allergy to interferon gamma or E. coli-derived products
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective barrier contraception

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy for metastatic disease
• At least 12 months since prior adjuvant chemotherapy

Endocrine therapy

• No concurrent corticosteroids

Radiotherapy

• At least 12 months since prior adjuvant radiotherapy

Surgery

• Not specified

Other

• No concurrent immunosuppressive drugs

New York
      Mount Sinai Medical Center, New York,  New York,  10029,  United States; Recruiting

Study chairs or principal investigators

Max W. Sung, MD,  Study Chair,  Mount Sinai Medical Center   

Study ID Numbers:  CDR0000064879; MTS-96322-ME; NCI-T96-0015O; NCT00002796
Record last reviewed:  December 2002
Last Updated:  February 24, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002796
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08