Expired Study
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New York, New York 10029


Purpose:

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


Study summary:

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.


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


Study is Available At:


Original ID:

NCI-2013-00038


NCT ID:

NCT00002796


Secondary ID:

96-322 ME*


Study Acronym:


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


Overall Status:

Terminated


Study Phase:

Phase 1/Phase 2


Genders:

Both


Minimum Age:

N/A


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

National Cancer Institute (NCI)


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:

Administratively complete.


Study Type:

Interventional


Study Design:

Endpoint Classification: Safety/Efficacy Study, I


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

46


Enrollment Type:

Actual


Overall Contact Information

Official Name:Max Sung
Principal Investigator
Mount Sinai School of Medicine

Study Dates

Start Date:May 1997
Primary Completion Date:December 2004
Primary Completion Type:Actual
Verification Date:January 2013
Last Changed Date:January 31, 2013
First Received Date:November 1, 1999

Study Outcomes

Outcome Type:Primary Outcome
Measure: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
Safety Issues:True
Outcome Type:Primary Outcome
Measure:Efficacy of FU in combination with PB, indomethacin and rhIFNg in patients with advanced colorectal cancer (Phase II)
Time Frame:Up to 7 years
Safety Issues:False

Study Interventions

Intervention Type:Drug
Name:fluorouracil
Description:Given IV
Arm Name:Treatment (fluorouracil, phenylbutyrate, indometha
Other Name:5-fluorouracil
Intervention Type:Drug
Name:sodium phenylbutyrate
Description:Given IV
Arm Name:Treatment (fluorouracil, phenylbutyrate, indometha
Other Name:Buphenyl
Intervention Type:Drug
Name:indomethacin
Description:Given orally
Arm Name:Treatment (fluorouracil, phenylbutyrate, indometha
Other Name:INDO
Intervention Type:Biological
Name:recombinant interferon gamma
Description:Given subcutaneously
Arm Name:Treatment (fluorouracil, phenylbutyrate, indometha
Other Name:Actimmune

Study Arms

Study Arm Type:Experimental
Arm Name:Treatment (fluorouracil, phenylbutyrate, indomethacin, IFN-G
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

Study Agencies

Agency Class:NIH
Agency Type:Lead Sponsor
Agency Name:National Cancer Institute (NCI)

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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