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

NCT00002796 | Terminated Phase 1

• 3 other identifiers: NCI-2013-0003896-322 ME*CDR0000064879
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (2)

• 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 (Phase I)

  1 week

• Efficacy of FU in combination with PB, indomethacin and rhIFNg in patients with advanced colorectal cancer (Phase II)

  Up to 7 years

Study Arms (1)

Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G

EXPERIMENTAL

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.

Drug: fluorouracil; Drug: sodium phenylbutyrate; Drug: indomethacin; Biological: recombinant interferon gamma

Interventions

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G

sodium phenylbutyrate DRUG

Given IV

Also known as: Buphenyl, sodium 4-phenylbutyrate

Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G

indomethacin DRUG

Given orally

Also known as: INDO, Indocin, Indometacin

Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G

recombinant interferon gamma BIOLOGICAL

Given subcutaneously

Also known as: Actimmune, gamma interferon, IFN-G

Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms

Interventions

Fluorouracil; 4-phenylbutyric acid; Indomethacin; Interferon-gamma; interferon gamma-1b

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Macrophage-Activating Factors; Lymphokines; Proteins; Biological Factors

Study Officials

• Max Sung

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: May 1, 1997
• Primary Completion: December 1, 2004
• Last Updated: February 1, 2013

Record last verified: 2013-01

Locations

US (1)