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

Primary Purpose

Mucinous Adenocarcinoma of the Colon, Mucinous Adenocarcinoma of the Rectum, Recurrent Colon Cancer

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
fluorouracil
sodium phenylbutyrate
indomethacin
recombinant interferon gamma
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mucinous Adenocarcinoma of the Colon

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Arm Label

Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
November 1, 1999
Last Updated
January 31, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00002796
Brief Title
Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer
Official Title
Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate, Indomethacin and Recombinant Human Interferon-Gamma in Advanced Colorectal Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Terminated
Why Stopped
Administratively complete.
Study Start Date
May 1997 (undefined)
Primary Completion Date
December 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-fluorouracil, 5-Fluracil, 5-FU
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
sodium phenylbutyrate
Other Intervention Name(s)
Buphenyl, sodium 4-phenylbutyrate
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
indomethacin
Other Intervention Name(s)
INDO, Indocin, Indometacin
Intervention Description
Given orally
Intervention Type
Biological
Intervention Name(s)
recombinant interferon gamma
Other Intervention Name(s)
Actimmune, gamma interferon, IFN-G
Intervention Description
Given subcutaneously
Primary Outcome Measure Information:
Title
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)
Time Frame
1 week
Title
Efficacy of FU in combination with PB, indomethacin and rhIFNg in patients with advanced colorectal cancer (Phase II)
Time Frame
Up to 7 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Max Sung
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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