Official Title: “Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer”

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.

Study Type: Interventional

Study Design: Treatment

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). - 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.

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.

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

Lead Sponsor: Mount Sinai School of Medicine

Mount Sinai Medical Center

New York New York 10029 United States

Overall Clinical Trial Officials and Contacts

Max W. Sung, MD Study Chair Mount Sinai School of Medicine  

Information obtained from ClinicalTrials.gov on July 18, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00002796

Study ID Number: CDR0000064879

ClinicalTrials.gov Identifier: NCT00002796

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database