Vaccine Therapy in Treating Patients With Kidney Cancer

Study Overview
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Brief Summary
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RATIONALE: Vaccines made from DNA may make the body build an immune response to kill tumor cells. PURPOSE: This randomized phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with kidney cancer.

Detailed Description
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OBJECTIVES: Primary Determine the safety and feasibility of vaccination with human and mouse prostate-specific membrane antigen (PSMA) DNA in patients with renal cell carcinoma. Determine the maximum tolerated dose of this regimen in these patients. Determine antibody responses to human PSMA in patients treated with this regimen. Secondary Assess antitumor response in patients treated with this regimen. OUTLINE: This is a randomized, dose-escalation study. Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive human prostate-specific membrane antigen (PSMA) DNA vaccine intramuscularly (IM) once every 3 weeks for 3 doses (doses 1-3). Patients then receive mouse PSMA DNA vaccine IM once every 3 weeks for 3 doses (doses 4-6). Arm II: Patients receive mouse PSMA DNA vaccine IM once every 3 weeks for 3 doses (doses 1-3). Patients then receive human PSMA DNA vaccine IM once every 3 weeks for 3 doses (doses 4-6). In both arms, treatment continues in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may receive additional booster vaccinations with the second form of PSMA DNA vaccine received (for doses 4-6) every 8 weeks for up to 4 additional doses. Cohorts of 3-6 patients per arm receive escalating doses of human and mouse PSMA DNA vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Patients are followed every 3 months for 2 years.

Official Title
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Injection of Renal Cell Carcinoma Patients With Human and Mouse Prostate Specific Membrane Antigen (PSMA) DNA: A Phase I Trial to Assess Safety and Immune Response

Conditions
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Kidney Cancer

Intervention / Treatment
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* Biological: human prostate-specific membrane antigen plasmid DNA vaccine
* Biological: mouse prostate-specific membrane antigen plasmid DNA vaccine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed renal cell carcinoma Patients with minimal disease burden are eligible provided they meet one or more of the following criteria: Prior nephrectomy and completely resected metastases Favorable-risk group, as defined by all of the following criteria: Karnofsky 80-100% Hemoglobin ≥ 13 g/dL (male) or ≥ 12 g/dL (female) Corrected calcium ≤ 10 mg/dL Prior nephrectomy Serum lactate dehydrogenase ≤ 200 μ/L Prior nephrectomy with metastases confined to lung and/or small volume metastatic disease (< 3 cm) exclusive of bone and liver No spinal, epidural, or CNS lesions No bone, liver or brain disease PATIENT CHARACTERISTICS: Age 18 and over Performance status See Disease Characteristics Karnofsky 80-100% Life expectancy Not specified Hematopoietic See Disease Characteristics WBC ≥ 3,500/mm^3 Hemoglobin ≥ 12.0 g/dL Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin < 2.0 mg/dL SGOT < 3.0 times upper limit of normal Renal See Disease Characteristics Creatinine ≤ 2.0 mg/dL OR Creatinine clearance ≥ 40 mL/min Cardiovascular No clinically significant cardiac disease No New York Heart Association class III or IV heart disease Pulmonary No severe debilitating pulmonary disease Other Fertile patients must use effective contraception No other active secondary malignancy within the past 5 years except non-melanoma skin cancer No infection requiring antibiotic treatment No narcotic- or steroid-dependent pain PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy At least 4 weeks since prior chemotherapy Endocrine therapy At least 4 weeks since prior corticosteroid therapy Radiotherapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy to only measurable lesion Surgery See Disease Characteristics No concurrent surgery Other Recovered from all prior therapy No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: human PSMA<br>Patients will receive a total of 6 vaccinations via the intramuscular route. Sites of injection should have intact lymphatic drainage. Groups of six patients will be randomized at each dose level, 3 for each arm, to receive either three immunizations with mouse PSMA followed by three immunizations with human PSMA or three immunizations with human PSMA followed by three immunizations with mouse PSMA. | Biological: human prostate-specific membrane antigen plasmid DNA vaccine<br> <br> Biological: mouse prostate-specific membrane antigen plasmid DNA vaccine<br> <br> |
| Experimental: mouse PSMA<br>Patients will receive a total of 6 vaccinations via the intramuscular route. Sites of injection should have intact lymphatic drainage. Groups of six patients will be randomized at each dose level, 3 for each arm, to receive either three immunizations with mouse PSMA followed by three immunizations with human PSMA or three immunizations with human PSMA followed by three immunizations with mouse PSMA. | Biological: human prostate-specific membrane antigen plasmid DNA vaccine<br> <br> Biological: mouse prostate-specific membrane antigen plasmid DNA vaccine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety |  | 2 years | 
| feasibility |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| antibody responses |  | 2 years | 
| anti-tumor response |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent renal cell cancer, stage I renal cell cancer, stage II renal cell cancer, stage III renal cell cancer, stage IV renal cell cancer