Vaccine Treatment of Kidney Cancer
Condition: Kidney Cancer
MeSH terms: Kidney Neoplasms; Carcinoma, Renal Cell
Intervention: 117-126:Fibroblast growth factor 5 (FGF-5); Fibroblast growth factor 5 (FGF-5):172-176/217-220; IL-2
Intervention description: Two 1 ml injection in the anterior thigh deep subcutaneous tissue within 2c of each other.; Two 1 ml injection in the anterior thigh deep subcutaneous tissue within 2c of each other.; 720,000 IU/kg as an intravenous bolus over a 15 minute period every 8 hours beginning on the day after immunization and continuing for up to 4 days (a maximum of 12 doses).
Intervention MeSH terms: Aldesleukin; Interleukin-2; Mitogens
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No
Keywords: Clinical Response; Toxicity; Immunologic Response; Adjuvant; IL-2; Renal Cancer

Summary:

      This study will evaluate the safety and side effects of two experimental vaccines in patients
      with kidney cancer and determine whether the vaccines "turn on" an immune response to the
      cancer. Each vaccine contains one of two peptides (pieces of proteins) from the fibroblast
      growth factor 5 (FGF-5) antigen, a protein produced by some cancer cells, and an oil-based
      liquid called Incomplete Freud's Adjuvant (Montanide ISA-51) that enhances the immune
      response to the vaccine.

      Patients 16 years of age and older who have kidney cancer that has spread beyond the kidney
      or whose primary kidney tumor has been removed within 6 months before entering the study and
      are at high risk for disease recurrence may be eligible for this study. Patients must have
      tissue type human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2) or human
      leukocyte antigen serotype within HLA-A A serotype group (HLA-A3) (determined by a blood test
      for human leukocyte antigen (HLA) typing) and their tumors must produce the FGF-5 peptide.
      Candidates are screened with a physical examination, blood and urine tests, electrocardiogram
      (EKG), tumor biopsy (removal of a small sample of tumor for examination) in patients whose
      tumor is easily accessible, and scans (computed tomography (CT), bone scans) and x-rays if
      current scans are not available.

      Participants are divided into two groups according to their HLA type (HLA-A2 or HLA-A3) to
      receive the vaccine appropriate for their HLA type. They are then further divided into three
      groups: 1) Group 1 includes patients who do not need or are ineligible for treatment with
      interleukin-2 (IL-2), a protein made by certain infection-fighting white cells that helps
      fight tumors) and patients who have previously had IL-2 therapy; 2) Group 2 includes patients
      who require immediate treatment with IL-2; and 3) Group 3 includes patients whose cancer has
      been surgically removed but who are at risk for recurrence.

      Patients in Groups 1 and 3 receive two peptide injections four times a week every 3 weeks for
      up to a year, or until their tumor grows (or returns in patients in Group 3) or the side
      effects are too severe to continue. Tumors are evaluated with a physical examination and
      scans or x-rays every 12 weeks and blood tests are done every 3 weeks. Patients in Group 2
      receive two peptide injections every day for 4 days, along with doses of IL-2 starting the
      day after the first peptide injection. The vaccines are given as injections under the skin of
      the thigh. IL-2 is infused through a vein over 15 minutes every 8 hours for up to 12 doses,
      depending on tolerance. The vaccine and IL-2 are repeated every 10 to 14 days, with tumor
      evaluations every 2 months. Patients stay in the hospital about 1 week during each treatment
      cycle to receive the IL-2.

      All patients undergo leukapheresis, a procedure for collecting large numbers of white blood
      cells. Blood is collected through a needle in an arm vein and flows through a cell separator
      machine, where the white cells are extracted. The rest of the blood is returned to the
      patient through the same needle or a needle in the other arm. The white cells are examined to
      evaluate how the vaccines change the action of immune cells. Some patients may undergo an
      additional biopsy of normal skin and tumor or lymph node to look at the effects of the
      vaccine on the immune cells in the tumor.

      Patients in Group 1 whose cancer grows and patients in Group C whose cancer returns may be
      offered IL-2 treatments as given to Group 2 patients, along with the peptide vaccine. If the
      disease responds to IL-2, the treatment may be repeated after 2 months.
    

Eligibility criteria:

        -  INCLUSION CRITERIA

        Patients will be screened for inclusion on this study while participating in the Surgery
        Branch protocol 99-C-0128: Evaluation for the National Cancer Institute (NCI) Surgery
        Branch Clinical Research Protocols

        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 fibroblast
        growth factor 5 (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 greater than or equal to 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 (reverse transcription
        polymerase chain reaction) and will only be eligible if it is detectable.

        Must be human leukocyte antigen serotype within HLA-A A serotype group (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.

        White blood cell (WBC) 3000/mm or greater.

        Platelet count 90,000mm^3 or greater.

        Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times
        normal.

        Eastern Cooperative Oncology Group (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 interleukin-2 (IL-2) (less than 600,000 IU/kg
        Food and Drug Administration (FDA) approved dosing regimen) will be eligible.

        For cohort A for each human leukocyte antigen (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 forced expiratory
        volume in 1 second (FEV1) greater than 60% predicted.

        Patients with electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia or
        arrhythmias or age greater than 50 years will have a normal stress cardiac test (stress
        thallium, stress multi-gated acquisition scan (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.

        White blood cell (WBC) 3000/mm^3 or greater.

        Platelet count 90,000 mm^3 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 Common
        Toxicity Criteria (CTC) 3); white blood cell (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 human immunodeficiency virus (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.