Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate in Advanced Colorectal Cancer
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT00002796 |
Recruitment Status :
Terminated
(Administratively complete.)
First Posted : January 27, 2003
Last Update Posted : February 1, 2013
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
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 | Drug: fluorouracil Drug: sodium phenylbutyrate Drug: indomethacin Biological: recombinant interferon gamma | Phase 1 Phase 2 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 46 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase I-II Study of Fluorouracil in Combination With Phenylbutyrate, Indomethacin and Recombinant Human Interferon-Gamma in Advanced Colorectal Cancer |
Study Start Date : | May 1997 |
Actual Primary Completion Date : | December 2004 |

Arm | Intervention/treatment |
---|---|
Experimental: 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. |
Drug: fluorouracil
Given IV
Other Names:
Drug: sodium phenylbutyrate Given IV
Other Names:
Drug: indomethacin Given orally
Other Names:
Biological: recombinant interferon gamma Given subcutaneously
Other Names:
|
- 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 ]
- Efficacy of FU in combination with PB, indomethacin and rhIFNg in patients with advanced colorectal cancer (Phase II) [ Time Frame: Up to 7 years ]

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | Child, Adult, Older Adult |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002796
United States, New York | |
Mount Sinai Medical Center | |
New York, New York, United States, 10029 |
Principal Investigator: | Max Sung | Icahn School of Medicine at Mount Sinai |
Responsible Party: | National Cancer Institute (NCI) |
ClinicalTrials.gov Identifier: | NCT00002796 |
Obsolete Identifiers: | NCT01925326 |
Other Study ID Numbers: |
NCI-2013-00038 96-322 ME* CDR0000064879 ( Registry Identifier: PDQ (Physician Data Query) ) |
First Posted: | January 27, 2003 Key Record Dates |
Last Update Posted: | February 1, 2013 |
Last Verified: | January 2013 |
Adenocarcinoma Rectal Neoplasms Colonic Neoplasms Adenocarcinoma, Mucinous Cystadenocarcinoma Recurrence Disease Attributes Pathologic Processes Colorectal Neoplasms Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Neoplasms Digestive System Diseases |
Gastrointestinal Diseases Colonic Diseases Intestinal Diseases Rectal Diseases Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms, Cystic, Mucinous, and Serous Interferons Interferon-gamma Indomethacin Fluorouracil 4-phenylbutyric acid Antimetabolites Molecular Mechanisms of Pharmacological Action |