Autologous Vaccination of Stage 4 Renal Cell Carcinoma Combined With Sunitinib

Study Overview
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Brief Summary
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While different lines of evidence support the notion that renal cell cancer is amenable for immunologic vaccination, up to now the clinical benefit associated with vaccines has been limited. One reason being probably the whole immunological state of the patients with RCC in which the tumor releases various substances promoting tolerance of the immune system towards the carcinoma. Recent data demonstrates that sunitinib has effects on the immune system which might enhance effectivity of anti tumor vaccines. Since in kidney cancer it is quite common to resect primary tumor when there are few metastasis or or metastatic tumor resected (if there are few metastasis), the investigators plan to use these tumor source to grow autologous carcinoma cell lines and use a method used world wide for many years and in our institution for over a decade to modify these cells by dinitro phenol and use irradiated cell for patients vaccination in combination with sunitinib treatments. The investigators will monitor clinical and immunological parameters in these patients.

Detailed Description
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Background: Renal cell carcinoma (RCC) constitutes around 3% of all solid tumors and cure for metastatic sidease is reported for less than 5% of patients. Together with melanoma it is considered the most immune responsive tumor, moreover it is a common practice to resect primary tumor or large metastasis even in the metastatic settings. Antiangiogenesis treatments are currently the favored antitumor drugs, however their use has rarely resulted in complete response/ cure. Recently it has been demonstrated that these drugs can elicit a shift in the immune environment in RCC patients (improved T1 responses reduced Treg responses).Our department has experience in the treatment 200 melanoma patients with cellular vaccination and in the preparation of primary tumor cell lines from various tumors including RCC. Interestingly , immune modulators such as antiCTLA-4 Ab have demonstrated impressive activity in patients previously vaccinated with cellular vaccinations. Working hypothesis: Vaccination with autologous cellular vaccines of RCC patients will induce clinical and immunological responses and help in formulation of better combined vaccination strategies in this cancer. Our aims are: 1) Growth and characterization of primary RCC cell lines,2)vaccination with autologous cellular vaccines in combination with sunitinib. 3) Clinical and immunologic characterizations for derivation of prognostic and predictive factors. Methods: primary or metastatic tumor resected in one of several Israeli hospitals will be used to derive autologous cell lines used for vaccinations following DNP modifications in combination with the regular Sunitinib treatments. Immunological and clinical followup of the patients will be performed and primary cell lines will be grown for further in-vitro testing including possible future use for allogeneic vaccines. Expected result Good safety profile combined with significant clinical and immunological responses are expected. Importance: This research might result in clinical benefit to the treated patients and will be important in the formulation of effective immune strategies in kidney cancer. Probable implications to Medicine: RCC vaccine in combination with other therapies has the potential to lead to longer survival and even cure the proposed study will help in the formulation of such a vaccine.

Official Title
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Phase1/2 Study of Vaccination With DNP Modified Autologous Renal Cell Carcinoma in Combination With Sunitinib in Stage 4 RCC

Conditions
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Renal Cell Cancer

Intervention / Treatment
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* Biological: Autologous renal cell vaccine based on DNP modified cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic renal cell cancer Primary/metastatic tumor for which resection seems of potential clinical benefit and fresh tissue can be obtained Patients for whom treatment with Sunitinib is the preferred clinical therapy Ecog <2 Willingness to participate in the trial and contribute small amounts ( up to 100cc for all the trial) of blood for immunological monitoring No concurrent active cancers ( excluding cancers which are not life threatening such as localized treated low grade prostate cancer,skin cancer etc) Exclusion Criteria: Age under 70 Life expectancy less than 3 months Large tumor burden at multiple organs

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 70 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologus vaccination with suntinib<br>Combination of autologous dnp irradiated modified cells with sunitinib treatments | Biological: Autologous renal cell vaccine based on DNP modified cells<br>* Primary or metastatic tumor resected in an Israeli hospital will be used to derive autologous cell lines used for vaccinations following DNP modifications in combination with the regular Sunitinib treatments. Immunological and clinical followup of the patients will be performed<br>* Other names: autologous vaccine for rcc tumors with sunitinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunological response to therapy |  | two years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| patients progression free survival |  | until end of 2011 | 
| dermatologic and allergic reactions to vaccine injections |  | during active treatments period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Renal cell cancer, sunitinib, autologous vaccine, metastatic RCC