NIH Clinical Research Studies

Protocol Number: 04-C-0259

Active Accrual, Protocols Recruiting New Patients

Title:
Immunization of Patients with Renal Cancer Using HLA-A2 and HLA-A3-Binding Peptides from Fibroblast Growth Factors 5 (FGF-5)
Number:
04-C-0259
Summary:
Patients with advanced clear cell renal cancer expressing FGF-5, will be given an HLA-appropriate peptide vaccination (117:126:FGF-5 for HLA-A2+ patients or FGF-5:172-176/217-220 for HLA-A3+) emulsified in Montanide ISA 51 in three cohorts. Cohort A will consist of patients with measurable metastatic disease who do not have an indication for immediate IL-2 therapy. They will receive vaccination every 3 weeks with clinical response to vaccination as primary endpoints, and immunological response as an important secondary endpoint. If tumor progression is documented, patients eligible to receive high-dose IL-2 will receive it along with continued peptide vaccine. Cohort B will admit patients with measurable metastatic disease who have indications for immediate IL-2 therapy. They will receive high-dose bolus IL-2 along with peptide in Montanide ISA 51 vaccine with clinical response to vaccination as primary endpoint and immunological response as an important secondary endpoint. Cohort C will consist of patients who have had high-risk primary tumors removed. They will receive the same HLA-appropriate peptide vaccination described above for up to one year or until tumor relapse is documented. Immunological response will be the primary endpoint for this cohort.
Sponsoring Institute:
National Cancer Institute (NCI)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
INCLUSION CRITERIA

Patients with clear cell renal carcinoma must fall into one of the two following groups:

For cohort A and B, patients must have measurable metastatic renal cancer and FGF-5 tumor expression. For cohort C, patients are required to have had a Stage III primary tumor (i.e. T3/T4 or N1/N2) excised within the last 6 months.

Patients must be age older than 16.

Expected survival must be greater than three months

Patients in cohorts A and B must have tumor sites safely accessible for biopsy or indications for resection of a site of tumor (e.g. an indicated nephrectomy or symptomatic metastasis) and have FGF-5 expression determined by RT-PCR and will only be eligible if it is detectable.

Must be HLA-A2+ or HLA-A3+.

Serum creatinine of 2.0 mg/dl or less.

Bilirubin 1.6 mg/dl or less, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl.

WBC 3000/mm or greater.

Platelet count 90, 000mm or greater.

Serum AST/ALT less then three times normal.

ECOG performance status of 0 or 1.

Patients of both genders must be willing to practice effective birth control during this trial and for three months after active treatment on this trial.

Patients who have received previous low dose IL-2 (less than 600,000 IU/kg FDA approved dosing regimen) will be eligible.

For cohort A for each HLA type, if there are no clinical responses to vaccine alone in the first 12 patients enrolled, subsequent patients must be eligible to receive high-dose IL-2.

Patients must be able to understand and sign the informed consent document.

Eligibility for administration of IL-2.

Patients must meet the following criteria to be eligible to receive IL-2:

Patients may not have active major medical illnesses such as cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

Patients with recent prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have a normal pulmonary function test as evidenced by a FEV1 greater than 60% predicted.

Patients with EKG abnormalities, symptoms of cardiac ischemia or arrhythmias or age greater than 50 years will have a normal stress cardiac test (stress thallium, stress MUGA, dobutamine echocardiogram or other stress test).

Patients must be willing to sign a durable power of attorney (DPA).

Serum creatinine of 2.0 mg/dl or less.

Total bilirubin 2.0 mg/dl or less, except in patients with Gilbert's syndrome who must have a total bilirubin less than 3.0 mg/dl.

WBC 3000/mm or greater.

Platelet count 90,000 mm or greater.

EXCLUSION CRITERIA:

Patients will be excluded:

Who are not willing or able to be biopsied.

Who are undergoing or have undergone in the past 3 weeks any other form of therapy for their cancer, or have undergone nitrosurea therapy within the past 6 weeks. All patients toxicities must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or local radiotherapy within the past 3 weeks as long as all toxicities have recovered to a grade 1 or less.

Have active systemic infections, coagulation disorder, or other major medical illnesses of the cardiovascular or respiratory symptoms or any known immunodeficiency disease (Immune competence will be defined as lymphocyte count greater than 500 (grade 3 toxicity in CTC 3); WBC 1000; and absence of opportunistic infections).

Who require systemic steroid therapy.

Who are pregnant (because of possible side effects on the fetus) or who are breastfeeding, or who are unwilling/unable to practice effective birth control.

Who are known to be positive for hepatitis BsAG, or HIV antibody, or hepatitis C antibody (unless antigen negative), (because of possible immune effects of these conditions).

Who have had a known allergic reaction to Incomplete Freund's Adjuvant (MONTANIDE ISA-51) or hypersensitivity to any agent used on this protocol.

Who have a fresh tumor specimen with no evidence of FGF-5 expression on a technically adequate RT-PCR assessment.

Special Instructions: Currently Not Provided
Keywords:
Clinical Response
Toxicity
Immunologic Response
Adjuvant
IL-2
Recruitment Keywords:
Renal Cancer
Conditions:
Investigational Drug(s):
117-126:FGF-5
FGF-5:172-176/217-220
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Rosenberg SA, et al. Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg. 1998 Sep;228(3):307-19.

Fisher RI, et al. High-dose aldesleukin in renal cell carcinoma: long-term survival update. Cancer J Sci Am. 1997 Dec;3 Suppl 1:S70-2.

van der Bruggen P, et al. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643-7.

Active Accrual, Protocols Recruiting New Patients

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