Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Vaccine Therapy in Treating Patients With Metastatic Kidney Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 18 and over NCI NCI-98-C-0139 NCI-T97-0081, T97-0081, NCT00019526

Objectives

1. Determine whether endogenous cellular or humoral immunity to a tumor-specific mutated von Hippel-Lindau (VHL) protein is present in patients with renal cell carcinoma.
2. Determine whether vaccination with synthetic peptide corresponding to the tumor's VHL mutation can induce or boost a patient's cellular immunity to that particular mutation.
3. Determine the type and characteristics of the cellular immunity generated in these patients.
4. Determine tolerance by the patients to this regimen.
5. Determine the toxicity spectrum of these peptides in these patients.
6. Determine the feasibility of expanding specific T-cell clones (peptide-activated lymphocytes) under guanosine monophosphate conditions.

Entry Criteria

Disease Characteristics:

• Histologically confirmed metastatic renal cell carcinoma for which there are no further chemotherapy or radiotherapy options known to increase survival



• Must have tumor tissue available for determination of von Hippel-Lindau (VHL) mutation
  • Must be found to have VHL mutation in tumor to receive treatment



• No history of CNS metastases

Prior/Concurrent Therapy:

Biologic therapy:

• At least 4 weeks since prior immunotherapy and recovered

Chemotherapy:

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy and recovered

Endocrine therapy:

• At least 4 weeks since prior steroids and recovered

Radiotherapy:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy and recovered

Surgery:

• Surgical biopsy of tumor tissue allowed

Patient Characteristics:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• More than 3 months

Hematopoietic:

• WBC at least 2,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• SGOT or SGPT no greater than 4 times normal
• Hepatitis B and C negative

Renal:

• Creatinine no greater than 2.0 mg/dL

Cardiovascular:

• No active ischemic heart disease (New York Heart Association class III or IV cardiac disease)
• No history of myocardial infarction within the last 6 months
• No history of congestive heart failure
• No ventricular arrhythmias or other arrhythmias requiring therapy

Immunologic:

• No prior autoimmune neutropenia, thrombocytopenia, or hemolytic anemia
• No prior systemic lupus erythematosus
• No prior Sjögren's syndrome
• No prior scleroderma
• No prior myasthenia gravis
• No prior Goodpasture's syndrome
• No prior Addison's disease
• No prior Hashimoto's thyroiditis
• No prior rheumatoid arthritis
• No prior multiple sclerosis
• No active Graves' disease
• HIV negative

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

Expected Enrollment

A total of 60 patients will be accrued for this study within 2-3 years.

Outcomes

Presence of endogenous cellular or humoral immunity
Induction of cellular immunity
Type and characteristics of cellular immunity
Tolerability
Toxicity
Feasibility of expanding specific T-cell clones

Outline

This is a randomized, pilot study. Patients are randomized to one of four treatment arms.

• Arm I (closed to accrual 12/31/01): Patients receive vaccination with peptide-pulsed antigen-presenting cells.



• Arm II: Patients receive mutant von Hippel-Lindau (VHL) peptide vaccination emulsified with Montanide ISA-51 (ISA-51) subcutaneously (SC).



• Arm III: Patients receive mutant VHL peptide and interleukin-2 emulsified with ISA-51 SC.



• Arm IV: Patients receive VHL peptide and sargramostim (GM-CSF) emulsified with ISA-51 SC.

Vaccinations are repeated in each arm every 4 weeks for a total of 4 vaccinations. Patients with stable or responding disease receive 2 additional vaccinations and may repeat treatment every 4 weeks in the absence of disease progression or unacceptable toxicity. If there is disease progression with a specific immunologic response after 4 vaccinations, patients have the option of receiving 2 additional vaccinations.

Patients are followed at 2 months and then every 2 months until disease progression.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research-Medical Oncology

Barry Gause, MD, Protocol chair		Ph: 301-594-9829 Email: gauseb@mail.nih.gov

Registry Information
Official Title		Vaccine Therapy With Tumor Specific Mutated VHL Peptides in Adult Cancer Patients With Renal Cell Carcinoma
Trial Start Date		1999-08-25
Registered in ClinicalTrials.gov		NCT00019526
Date Submitted to PDQ		1998-08-13
Information Last Verified		2007-01-08