Immunotherapy Study for Metastatic Renal Cell Cancer
In this Phase 1 Trial investigators plan to establish the MTD of HyperAcute®-Renal (HAR) immunotherapy in subjects with clinically metastatic renal cell carcinoma.
Metastatic Renal Cell Carcinoma
Metastatic Clear-cell Renal Cancer
Recurrent Renal Cell Carcinoma
Refractory Renal Cell Carcinoma
Metastatic Kidney Cancer
Biological: HyperAcute®-Renal (HAR) Immunotherapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of HyperAcute-Renal (HAR) Immunotherapy In Patients With Metastatic Renal Cell Cancer|
- Toxicity [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]To determine the toxicity (side-effects, dose-limiting toxicity [DLT] and maximum tolerated dose [MDT]) of administration of HyperAcute®- Renal (HAR) immunotherapy cells administered by intradermal injection into patients with recurrent or refractory, metastatic clear-cell renal cancer.
- Immunological Correlative Studies [ Time Frame: 3 months ] [ Designated as safety issue: No ]To conduct correlative scientific studies of patient samples to determine the mechanism of any observed anti-tumor effect. In these studies human humoral and cellular immune responses to HAR cells will be evaluated in blood specimens pre and post immunotherapy for microenvironmental immune modulation.
- Progression-Free Survival [ Time Frame: 3 months ] [ Designated as safety issue: No ]To assess the tumor response rate (progression-free survival) of anti-tumor immunization with HyperAcute®-Renal.
|Study Start Date:||March 2014|
|Estimated Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
Experimental: HyperAcute®-Renal Immunotherapy
Cells will be injected intradermally every 1 week x 4 weeks and then every 2 weeks for 10 immunizations to total 14 immunizations. Dose Cohort 1 will receive 150 million cells per immunization; Dose Cohort 2 will receive 300 million cells per immunization. Once the first three months of immunizations are completed, patients may receive other systemic treatment (non-investigational) while continuing to receive the remaining 6 immunizations.
Biological: HyperAcute®-Renal (HAR) Immunotherapy
HyperAcute®-Renal Immunotherapy consisting of equal cell doses of each of two allogeneic renal cell cancer cell lines (HAR1 and HAR2) engineered to express the murine α(1,3)GT gene.
Cells will be injected intradermally every 1 week x 4 weeks and then every 2 weeks for 10 immunizations to total 14 immunizations. Dose Cohort 1 will receive 150 million cells per immunization; Dose Cohort 2 will receive 300 million cells per immunization.
Unfortunately, despite the best clinical efforts with surgical intervention and chemotherapy many patients with high grade and advanced stage renal cell carcinoma (RCC) progress and die of their disease. In United States approximately 13,000 individuals die from RCC each year. The primary cause of failure is microscopic spread of the tumor prior to complete surgical extirpation of detectable disease and the heterogenous nature of the metastatic cells. These cells are resistant to all forms of therapy including chemotherapy, radiation, and escape from immune surveillance by a variety of mechanism. This results in low 5-year survival rates (approximately 10%) in patients with metastasis. Novel immunotherapeutic strategies provide a hope in circumventing the drug resistant RCC and improve the survival of patients undergoing surgery. RCC, like melanoma is one of the most immunogenic tumors and partial successes have been achieved by a variety of immunotherapeutic strategies show partial successes. Although vaccines have been highlighted in clinical trials since the mid-1970s with subcutaneous autologous irradiated tumor cells most of these studies were in patients with advanced disease. These approaches resulted in rare if any clinically relevant benefits to patients. However, new vaccines in other cancers have shown responses equivalent to chemotherapy with minimal toxicity . The use of immune adjuvant strategies to increase the therapeutic immune responses to tumor vaccines enhanced the proportion of patients with therapeutic responses to vaccination to 10%-15% on average. Only during the last decade has it become clear that failure of immune system to respond to the tumor vaccine is the main obstacle that limits the efficacy of vaccine based immunotherapies. The precise reason for failure of the immune system in cancers is very complex particularly as it relates to (1) the escape of growing or metastasizing tumor from immune surveillance [2-4] and (2) low immunogenicity of autoantigens associated with malignant neoplasms. This human clinical trial will investigate the dose limiting toxicity of a polyvalent immune enhanced vaccine as a first step towards developing a multipronged approach to triggering the immune system to attack and destroy micrometastatic disease. Investigators hypothesize that the allogeneic RCC cell genetically modified to express α (1,3)galactosyltransferase (enzyme responsible for producing the strong xenoantigen on the cell surface of the cellular immunotherapy) will augment the efficacy of cellular immunotherapy and thereby improve patient outcomes. In this Phase 1 Trial investigators plan to establish the maximum tolerated dose (MTD) of Hyperacute®-Renal (HAR) immunotherapy in subjects with clinically metastatic renal cell carcinoma.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02035358
|Study Director:||Nicholas Vahanian, MD||NewLink Genetics Incorporation|