Vaccine Treatment for Hormone Refractory Prostate Cancer
This 2-phase study will determine the safety of treating patients with prostate cancer with the genetically engineered HyperAcute-Prostate cancer vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed prostate cancer cells containing a mouse gene that causes the production of a foreign pattern of protein-sugars on the cell surface. It is hoped that the immune response to the foreign substance will stimulate the immune system to attack the patient's own cancer cells that have similar proteins without this sugar pattern, causing the tumor to remain stable or shrink.
Patients 19 years of age or older with hormone refractory prostate cancer that has recurred or no longer responds to standard treatment may be eligible for this study. Candidates will be screened with medical history and physical examination, blood tests, urinalysis, chest x-rays and CT scans. MRI, PET, and ultrasound scans may be obtained if needed.
Participants will receive twelve vaccinations two weeks apart from each other. The vaccines will be injected under the skin, similar to the way a tuberculosis skin test is given. Phase I of the study will treat successive groups of patients with increasing numbers of the vaccine cells to evaluate side effects of the treatment and determine the optimum dose. Phase II will look for any beneficial effects of the vaccine given at the highest dose found to be safe in Phase I. Monthly blood samples will be drawn during the 6 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 2 months for the remaining first year (6 months) after vaccination and then every 3 months for the next 2 years for the following tests and procedures to evaluate treatment response and side effects:
- Medical history and physical examination
- Blood tests
- X-rays and various scans (nuclear medicine/CT/MRI)
- FACT-P Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, monthly during treatment, and during follow-up visits after completing the treatment. It includes questions on the severity of prostate cancer symptoms and the ability to perform normal activities of daily life.
Biological: HyperAcute-Prostate Cancer Vaccine
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of an Antitumor Vaccination Using Alpha (1,3) Galactosyltransferase Expressing Allogeneic Tumor Cells in Patients With Hormone Refractory Prostate Cancer|
- Safety and efficacy of administration of HyperAcute-Prostate (HAP) cancer cells by injection into men with hormone refractory prostate carcinoma [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
- Correlative scientific studies of patient samples to determine the mechanism of any observed anti-tumor effect [ Time Frame: 6 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2005|
|Study Completion Date:||September 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
|Experimental: vaccine group||
Biological: HyperAcute-Prostate Cancer Vaccine
Before enrollment in the Phase I and Phase II- Arm A studies, the patient must be determined to have measurable disease with biopsies on first recurrence or bone metastases. In the Phase II- Arm B study, patients will be men with non-measurable progressive disease as evidenced by elevated PSA only. Cells will be injected intradermally every two weeks for 12 cycles on a prime-boost regimen. Dosage will vary from 30 million to 500 million HAP cells.
Prostate cancer is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimated that there were about 230,900 new cases of prostate cancer in the United States in the year 2004. About 29,900 men will die of this disease. Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer. This protocol attempts to exploit an approach to prostate cancer immunotherapy using a naturally occurring barrier to xenotransplantation in humans in an attempt to vaccinate patients against their prostate cancer. The expression of the murine alpha (1,3) galactosyltransferase [alpha (1,3) GT] gene results in the cell surface expression of alpha (1,3) galactosyl-epitopes (alpha-gal) on membrane glycoproteins and glycolipids. These epitopes are the major target of the hyperacute rejection response that occurs when organs are transplanted from non-primate donor species into man. Human hosts often have pre-existing anti-alpha-gal antibodies that bind alpha-gal epitopes and lead to rapid activation of complement and cell lysis. The pre-existing anti-alpha-gal antibodies found in most individuals are thought to be due to exposure to alpha-gal epitopes that are naturally expressed on normal gut flora leading to chronic immunological stimulation. These antibodies may comprise up to 1% of serum IgG. In this Phase I/II trial, patients with hormone refractory prostate cancer will undergo a series of twelve intradermal injections with a vaccine composed of irradiated allogeneic prostate cancer cell lines (HAP-1 and HAP-2) that have been transduced with a recombinant Moloney murine leukemia virus (MoMLV)-based retroviral vector expressing the murine alpha (1,3) GT gene. Endpoints of the study include determination of dose-limiting toxicity (DLT), maximum tolerated dose (MTD), tumor and immunological responses.
|United States, Nebraska|
|University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198|
|Study Chair:||Charles J. Link, M.D.||NewLink Genetics Corporation|