Vaccine Treatment of Kidney Cancer

NCT00089778 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 04025904-C-0259
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Kidney Cancer

Keywords

Clinical Response; Toxicity; Immunologic Response; Adjuvant; IL-2; Renal Cancer

Outcome Measures

Primary Outcomes (3)

• Response

  Overall response is defined as the best response (e.g. complete response...) recorded from the start of treatment until disease progression/recurrence. Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive disease is at least a 20% increase in the sum of LD of target lesions since the treatment started or the appearance of new lesion. Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease.

  3 years and 9 months

• Count of Participants With Adverse Events

  Here is the number of participants with adverse events. For the detailed list of adverse events, see the adverse event module.

  47 months

• Immunologic Response to Peptide Vaccination Pre and Post Vaccination

  FGF-5 specific CTL (cytotoxic T lymphocytes) may be tested by cytokine release assay or ELISPOT (enzyme linked immunosorbent spot) assay using tumor, FGF-5 transfected or peptide-loaded target cells and compared to pre-treatment peripheral blood mononuclear cells (PBMC) to determine immune response to vaccination. In the assays, differences of 2-3 fold are indicative of true biologic difference.Due to text data entry field limitations, Pre vaccination and post vaccination will be shown in the results as Pre V and Post V, respectively. Patients entered in Group A did not complete sufficient vaccinations to permit immunological evaluation and in Group B, the co-administration of IL-2 is known to corrupt immunological evaluation (so only clinical responses are valid). Expanding information on cancer vaccines in general as wells as preliminary information from this trial on FGF-5 as a vaccine target both served to render the enrollment of additional patients to this trial obsolete.

  24 hours

Study Arms (3)

Grp A-Measurable metastatic disease (no immediate aldesleukin)

EXPERIMENTAL

Patients who do not need or are ineligible for treatment with interleukin-2 (IL-2) and patients who have previously had IL-2 therapy. A3 FGF-5 (Fibroblast growth factor 5): 172-176/217-220 peptide - two 1 ml injections in the anterior thigh deep subcutaneous tissue within 2c of each other.

Drug: Fibroblast growth factor 5 (FGF-5):172-176/217-220

Grp B - Measurable metastatic disease that require aldesleukin

EXPERIMENTAL

Patients who require immediate treatment with IL-2. A2 FGF-5: 117-126 peptide + HD (high dose) IL-2 (prior cycle 1)- 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).

Drug: 117-126:Fibroblast growth factor 5 (FGF-5); Other: IL-2

Grp C - High-risk loco-regional disease

EXPERIMENTAL

Patients whose cancer has been surgically removed but who are at risk for recurrence and local disease and who are seeking experimental adjuvant therapy. A2 FGF-5: 117-126 peptide (adjuvant); A3 FGF-5: 172-176/217-220 peptide (adjuvant)

Drug: 117-126:Fibroblast growth factor 5 (FGF-5)

Interventions

117-126:Fibroblast growth factor 5 (FGF-5) DRUG

Two 1 ml injection in the anterior thigh deep subcutaneous tissue within 2c of each other.

Also known as: MLSVLEIFAV

Grp B - Measurable metastatic disease that require aldesleukin; Grp C - High-risk loco-regional disease

Fibroblast growth factor 5 (FGF-5):172-176/217-220 DRUG

Two 1 ml injection in the anterior thigh deep subcutaneous tissue within 2c of each other.

Also known as: NTYASPRFK

Grp A-Measurable metastatic disease (no immediate aldesleukin)

IL-2 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).

Also known as: Interleukin-2, Aldesleukin

Grp B - Measurable metastatic disease that require aldesleukin

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• van der Bruggen P, Traversari C, Chomez P, Lurquin C, De Plaen E, Van den Eynde B, Knuth A, Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643-7. doi: 10.1126/science.1840703.

  PMID: 1840703 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page
• Common Toxicity Criteria version 3.0 (CTCv3)

MeSH Terms

Conditions

Kidney Neoplasms

Interventions

Fibroblast Growth Factor 5; Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Fibroblast Growth Factors; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interleukins; Cytokines; Lymphokines

Results Point of Contact

• Title: James Yang, M.D.
• Organization: National Cancer Institute (NCI), National Institutes of Health (NIH)

jamesyang@mail.nih.gov

301-496-1574

Study Officials

• James Yang, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 12, 2004
• First Posted: August 13, 2004
• Study Start: September 10, 2004
• Primary Completion: August 5, 2008
• Study Completion: August 5, 2008
• Last Updated: August 1, 2017
• Results First Posted: October 11, 2012

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)