Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer

NCT ID: NCT00002796

Last Updated: 2013-02-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1997-05-31

Brief Summary

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. 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

Detailed Description

PRIMARY OBJECTIVES:

I. To determine in a Phase I study the toxicity of flurouracil (FU) when given in escalating doses in combination with fixed doses of phenlylbutyrate (PB), indomethacin and recombinant human interferon-gamma (rhIFNg) to patients with advanced colorectal cancer.

II. To determine in a Phase II study the efficacy of FU in combination with PB, indomethacin and rhIFNg in patients with advanced colorectal cancer.

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.

Conditions

Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Recurrent Colon Cancer; Recurrent Rectal Cancer; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

fluorouracil

Intervention Type: DRUG

Given IV

sodium phenylbutyrate

Intervention Type: DRUG

Given IV

indomethacin

Intervention Type: DRUG

Given orally

recombinant interferon gamma

Intervention Type: BIOLOGICAL

Given subcutaneously

Interventions

fluorouracil

Given IV

Intervention Type: DRUG

sodium phenylbutyrate

Given IV

Intervention Type: DRUG

indomethacin

Given orally

Intervention Type: DRUG

recombinant interferon gamma

Given subcutaneously

Intervention Type: BIOLOGICAL

Other Intervention Names

5-fluorouracil; 5-Fluracil; 5-FU; Buphenyl; sodium 4-phenylbutyrate; INDO; Indocin; Indometacin; Actimmune; gamma interferon; IFN-G

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Max Sung

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

96-322 ME*

Identifier Type: -

Identifier Source: secondary_id

CDR0000064879

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2013-00038

Identifier Type: -

Identifier Source: org_study_id

NCT01925326

Identifier Type: -

Identifier Source: nct_alias