Vaccine Treatment for Advanced Breast Cancer
This 2-phase study will determine the safety of treating patients with breast cancer with the genetically engineered HyperAcute-Breast cancer vaccine. It will establish the proper vaccine dose and will examine side effects and potential benefits of the treatment. The vaccine contains killed breast 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 18 years of age or older with breast 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 four vaccinations a month 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. Weekly blood samples will be drawn during the 4 months of vaccine treatment. In addition, patient follow-up visits will be scheduled every 2 months for the first year 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-B Assessment questionnaire to measure the impact of treatment on the patient's general well-being. The questionnaire is administered before beginning treatment, before each vaccination, and during follow-up visits after completing the treatment. It includes questions on the severity of breast cancer symptoms and the ability to perform normal activities of daily life.
Biological: HyperAcute - Breast 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 Relapsed or Refractory Breast Cancer|
- To determine the safety and efficacy of administration of HyperAcute Breast (HAB) cancer cells by injection into women with recurrent or refractory breast carcinoma [ Time Frame: 4 months ] [ Designated as safety issue: Yes ]
- To conduct correlative scientific studies of patient samples to determine the mechanism of any observed anti-tumor effect. [ Time Frame: 4 months ] [ Designated as safety issue: No ]
|Study Start Date:||August 2004|
|Study Completion Date:||September 2007|
|Primary Completion Date:||September 2007 (Final data collection date for primary outcome measure)|
|Experimental: Vaccine group||
Biological: HyperAcute - Breast cancer vaccine
Cells will be injected intradermally for four weeks for four cycles. Dosage will vary from 10 million to 100 million HAB cells.
Other Name: HAB-1 and HAB-2 vaccine components
According to 2002 statistics of the American Cancer Society, an estimated 203,500 individuals will be diagnosed with breast cancer and 39,600 will die of the disease this year despite all current therapy. This protocol attempts to exploit an approach to breast cancer gene therapy using a naturally occurring barrier to xenotransplantation in humans in attempt to vaccinate patients against their breast 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 relapsed or refractory breast cancer will undergo a series of four intradermal injections with a vaccine composed of irradiated allogeneic breast cancer cell lines (HAB-1 and HAB-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, Iowa|
|Medical Oncology Hematology Associates|
|Des Moines, Iowa, United States, 50309|
|Study Chair:||Charles J. Link, Jr., M.D.||NewLink Genetics Corporation|