Clinical trial NCT00890110: Autologous Vaccination of Stage 4 Renal Cell Carcinoma Combined With Sunitinib
Official title: Phase1/2 Study of Vaccination With DNP Modified Autologous Renal Cell Carcinoma in Combination With Sunitinib in Stage 4 RCC
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Renal Cell Cancer
Keywords: Renal cell cancer
sunitinib
autologous vaccine
metastatic RCC
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2009-04-29
Enrollment: 13
Sex: ALL
Minimum age (years): 15
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: immunological response to therapy
timeFrame: two years
Secondary outcomes:
measure: patients progression free survival
timeFrame: until end of 2011
measure: dermatologic and allergic reactions to vaccine injections
timeFrame: during active treatments period
Other outcomes:
Locations:
Study officials:
affiliation: Hadassah Medical Organization
name: Hovav Nechushtan, MD PHD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lotem M, Shiloni E, Pappo I, Drize O, Hamburger T, Weitzen R, Isacson R, Kaduri L, Merims S, Frankenburg S, Peretz T. Interleukin-2 improves tumour response to DNP-modified autologous vaccine for the treatment of metastatic malignant melanoma. Br J Cancer. 2004 Feb 23;90(4):773-80. doi: 10.1038/sj.bjc.6601563.
citation: Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, Dreicer R, Bukowski R, Finke JH. Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res. 2009 Mar 15;15(6):2148-57. doi: 10.1158/1078-0432.CCR-08-1332. Epub 2009 Mar 10.
citation: Hutson TE, Figlin RA, Kuhn JG, Motzer RJ. Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies. Oncologist. 2008 Oct;13(10):1084-96. doi: 10.1634/theoncologist.2008-0120. Epub 2008 Oct 6.