Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed over 18 MSKCC-88119 NCI-V89-0008

Objectives

I.  Determine the toxicity of interleukin-1-beta (IL-1B) given as a 30-minute 
infusion, once a day for two consecutive days, in patients with advanced 
colorectal cancer.
II.  Determine the maximum tolerated dose of IL-1B on this regimen.
III.  Determine the effect on circulating leukocytes and platelets of 
intravenous IL-1B by itself and following chemotherapy with 5-fluorouracil.
IV.  Determine the effect of intravenous IL-1B on bone marrow cellularity and 
function.
V.  Determine the pharmacokinetics of IL-1B during and following a 30-minute 
intravenous infusion.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients over 18 years of age with 
histologically proven Dukes Stage D colon or colorectal carcinoma who are 
scheduled to receive chemotherapy with 5-fluorouracil (administered over 3 
consecutive days q 4 weeks) and who are judged physically able to tolerate the 
treatment; histology will be confirmed at Memorial Sloan-Kettering Cancer 
Center.  No prior radiotherapy, chemotherapy (including 5-fluorouracil), or 
therapy with other recombinant biologic products (including interleukin-2, 
colony stimulating factors, interferons, and tumor necrosis factor) is 
allowed.  Patients who have received any bone marrow stimulants, including 
lithium or steroid hormones, are ineligible, as are those who have any bone 
marrow involvement with tumor.  A Karnofsky performance status of better than 
60% and a life expectancy of at least 3 months are required.  Adequate 
hematologic, hepatic, and renal function must be demonstrated by the following 
parameters:  WBC at least 3,000 but less than 11,000, absolute neutrophils at 
least 1,500 but less than 10,000, and platelets greater than 150,000; total 
bilirubin no more than 1.5 mg/dl and no metastasis involving greater than 60% 
of the liver (documented on CT scan); and serum creatinine less than 1.5 mg/dl 
and/or creatinine clearance at least 70 ml/minute/1.73 sqm.  The following 
conditions exclude:  clinical evidence of cardiovascular disease, including 
congestive heart failure, angina, history of hypertension (diastolic blood 
pressure greater than 90 mmHg or requirement for antihypertensives), history 
of myocardial infarction, history of stroke, arrhythmias, or other cardiac 
dysfunction; another malignancy; autoimmune disease; organ allograft; serious 
active infection not controlled by antibiotics; and known or suspected CNS 
disease, including CNS metastases, history of epilepsy, and other CNS disorder 
or psychiatric dysfunction.  Women of childbearing potential (premenopausal) 
or who are pregnant or lactating are excluded; men will be cautioned to use 
barrier contraception during and for 90 days following treatment.

Expected Enrollment

Approximately 30 patients will be entered.

Outline

Nonrandomized study.  All patients sequentially receive all regimens, toxicity 
permitting.
Regimen A:  Biological Response Modifier Therapy.  Interleukin-1-beta, IL-1B.
Regimen B:  Single-agent Chemotherapy.  5-Fluorouracil, 5-FU, NSC-19893.
Regimen C:  Single-agent Chemotherapy plus Biological Response Modifier 
Therapy/Hematologic Toxicity Attenuation.  5-FU; plus IL-1B.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Nancy Kemeny, MD, Protocol chair		Ph: 212-639-8068; 800-525-2225