Vaccine Therapy Before Surgery in Treating Patients With Localized Kidney Cancer

Not Applicable

Terminated

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

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

Registration Number: NCT02170389

Lead Sponsor: Roswell Park Cancer Institute

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (AGS-003 immunotherapy, nephrectomy)	Renal Cell Carcinoma/CD40L RNA-Transfected Autologous Dendritic Cell Vaccine AGS-003	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.
Treatment (AGS-003 immunotherapy, nephrectomy)	Nephrectomy	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.
Treatment (AGS-003 immunotherapy, nephrectomy)	Laboratory Biomarker Analysis	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.

Primary Outcome Measures

Name	Time	Method
Change in Immune Marker Expression Levels	Baseline to up to 30 days post-nephrectomy	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.

Secondary Outcome Measures

Name	Time	Method
Adverse Event Rates as Graded by the Common Terminology Criteria for Adverse Events Version 4.0	Up to 30 days	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.