Vaccine Therapy Before Surgery in Treating Patients With Localized Kidney Cancer

Study Overview
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Brief Summary
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This pilot clinical trial studies vaccine therapy before surgery in treating patients with kidney cancer that has not spread to nearby lymph nodes or to other parts of the body. Vaccines made from a person's tumor cells and white blood cells may help the body build an effective immune response to kill tumor cells when they are infused back into the body.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the immune-modulatory systemic and intratumoral effects of AGS-003 (renal cell carcinoma/cluster of differentiation [CD]40L ribonucleic acid [RNA]-transfected autologous dendritic cell vaccine AGS-003) as neoadjuvant treatment in patients with localized renal cell carcinoma. SECONDARY OBJECTIVES: I. To assess the feasibility that total tumor RNA processing-related activities meet specifications for AGS-003 manufacturing utilizing a core needle biopsy procedure for tumor harvesting prior to nephrectomy. OUTLINE: Patients receive 3 injections of renal cell carcinoma/cluster of CD40L RNA-transfected autologous dendritic cell vaccine AGS-003 intradermally (ID) once every 7 days during weeks 6-8 in the absence of disease progression or unacceptable toxicity. Patients then undergo partial or radical nephrectomy on week 10. After completion of study treatment, patients are followed up at 1 month.

Official Title
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Neoadjuvant AGS-003 Immunotherapy in Patients With Localized Kidney Cancer &lt;pT2

Conditions
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Recurrent Renal Cell Carcinoma, Stage I Renal Cell Cancer, Stage II Renal Cell Cancer

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Procedure: Nephrectomy
* Biological: Renal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have localized non-metastatic renal cell carcinoma (RCC) (< pT2, NO, MO), as per the American Joint Committee on Cancer (AJCC) seventh (7th) edition criteria Must be surgical candidates as deemed fit by surgeon Patients of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately Willingness to undergo leukapheresis and biopsy procedures for the autologous components (peripheral blood mononuclear cells, plasma and fresh tumor specimen) required for manufacture of AGS-003 Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (e.g., shortness of breath, fatigue, orthopnea, paroxysmal nocturnal dyspnea), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Radiation to primary tumor prior to enrollment in this study Pregnant or nursing female patients Unwilling or unable to follow protocol requirements Active autoimmune disease or condition requiring chronic immunosuppressive therapy (e.g., rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, organ transplant recipient, etc.) NOTE: abnormal laboratory values for autoimmunity markers in the absence of other signs/symptoms of autoimmune disease are not exclusionary Known clinically significant infections, including human immunodeficiency virus (HIV) and active hepatitis B or C Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive treatment (i.e., any significant medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk by participating in this study) Chronic use of systemic corticosteroids (i.e., >= 10 mg/day prednisone or equivalent) Received an investigational agent within 30 days prior to enrollment

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (AGS-003 immunotherapy, nephrectomy)<br>Patients receive 3 injections of renal cell carcinoma/cluster of CD40L RNA-transfected autologous dendritic cell vaccine AGS-003 ID once every 7 days during weeks 6-8 in the absence of disease progression or unacceptable toxicity. Patients then undergo partial or radical nephrectomy on week 10. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Nephrectomy<br>* Undergo partial or radical nephrectomy<br>Biological: Renal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003<br>* Given ID<br>* Other names: AGS-003;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Immune Marker Expression Levels | The time component will be modeled as a three-level classification factor. The full model for the effects of time will be fit using linear mixed model methods. The model will include a random patient effect and 5 fixed effects for time and the interactions. The presence of any time effect will be assessed with full-reduced model type 3 test. If the omnibus test is statistically significant at the p < 0.05 level, then three pairwise time-point comparisons will be conducted. Expression measurements may be transformed to satisfy modeling assumptions. | Baseline to up to 30 days post-nephrectomy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0 | Summarized in all patients who received AGS-003. These rates will be described as the proportion of patients with the event, by grade, and supported with exact 95% confidence intervals. | Up to 30 days |