PSA-Based Vaccine and Radiotherapy to Treat Localized Prostate Cancer
This study will test the ability of an experimental vaccine to increase the number of tumor-fighting immune cells (lymphocytes) in patients with localized prostate cancer and prevent the disease from recurring following radiation therapy. The vaccine is intended to stimulate lymphocytes to target and attack cells containing a protein called prostate specific antigen, or PSA. It is composed of the following parts:
- rV-PSA: Vaccinia virus plus human DNA that produces PSA (prostate specific antigen)
- rV-B7.1: Vaccinia virus plus human DNA that produces B7.1 (a protein that helps guide immune cells to their targets)
- rF-PSA: Fowlpox virus plus human DNA that produces PSA
- GM-CSF: Drug that boosts the immune system.
- IL-2: Drug that boosts the immune system.
Patients 18 years of age and older with prostate cancer confined to the prostate who have received a smallpox vaccine sometime in the past and who do not have a history of allergy to eggs may be eligible for this study. Candidates are screened with a complete medical history and physical examination, blood tests, and skin tests (similar to those for allergies or tuberculosis) to assess immune function.
Participants are randomly assigned to receive one of the following three treatments: Group 1 - standard radiation therapy plus the experimental vaccine; Group 2 - standard radiation therapy without the vaccine; Group 3 - standard radiation therapy with the vaccine, but with a different dose of IL-2 from Group 1.
Patients in the vaccine groups receive injections in the arm or thigh in 28-day treatment cycles, as follows:
- GM-CSF: Days 1 through 4 of the first week
- IL-2 5: for Group 1, 5 days in the second week of each cycle; for Group 3, 14 days beginning in the second week of each cycle
- rV-PSA and rV-B7.1: Day 2 of the first cycle only
- rF-PSA (booster shots): Every 28 days, beginning day 2 of the second cycle (i.e., days 30, 58, 86, etc.)
Treatment continues for eight cycles unless serious side effects develop, PSA levels rise significantly, or the doctors feel there is no reason to continue therapy.
All patients undergo radiation therapy and possibly hormone therapy, if indicated. Blood samples are drawn once a week for the first month and then once every 4 weeks to monitor safety. After treatment ends, patients are followed with examinations and blood tests every 3 months for the first 2 years and then every 6 months until the doctors determine follow-up is no longer needed or the cancer returns.
All patients have HLA tissue typing at the beginning of the study. Those who are type HLA-A2 are asked to have additional procedures for studying the immune response that can be done only with this tissue type. This involves collecting blood samples before treatment begins, every 4 weeks during treatment, once after cycle 2, and once 4 months after the eighth vaccine. They also undergo four leukapheresis procedures for collecting white blood cells. For leukapheresis, blood is collected through a needle in an arm vein, similar to donating a unit of blood. The blood flows through a machine that separates it into its components. The white cells are removed, and the red cells, platelets and plasma are returned to the body, either through the same needle or through a needle in the other arm.
|Study Design:||Primary Purpose: Treatment|
|Official Title:||A Randomized Phase II Study of a PSA-Based Vaccine in Patients With Localized Prostate Cancer Receiving Standard Radiotherapy|
|Study Start Date:||June 2000|
|Study Completion Date:||December 2005|
This trial will evaluate the immunologic effects of a vaccination regimen in HLA-A2 positive prostate cancer patients. Eligible patients will have localized prostate cancer and be willing to undergo definitive local radiotherapy. 30 patients will be randomized in a 2:1 ratio into two cohorts (see schema below) with patients in the vaccine arm receiving vaccination before, during and after primary standard radiotherapy (external beam alone or in combination with brachytherapy). When enrollment to these two cohorts is complete, enrollment will begin with up to 19 (9-10 HLA-A2 positive) patients to a third, non-randomized vaccine cohort. This cohort C will differ from the first vaccine cohort only in the IL-2 dose and schedule. The vaccine regimen will be composed of (1) a recombinant vaccinia virus that expresses the Prostate Specific Antigen gene (rV-PSA), admixed with (2) a recombinant vaccinia virus that expresses B7.1 costimulatory molecule (rV-B7.1); followed by (3) sequential vaccinations with recombinant fowlpox virus containing the PSA gene (rF-PSA). All patients on the vaccine arms will, in addition, receive sargramostim and aldesleukin as part of their vaccination schedule.
The primary endpoint is to identify immunologic response as measured by in vitro analysis of the patients peripheral blood cells. The immune response of cohorts A and B will be analyzed at various times to determine whether a specific immune response can be affected by the vaccination as well as whether radiotherapy has an effect on that immune response. The serum PSA will be followed as a secondary endpoint.
All patients with PSA-expressing adenocarcinoma of the prostate will be evaluated for eligibility that includes a history of prior vaccinia (as vaccine against smallpox) and immunocompetence.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005916
|United States, Maryland|
|National Cancer Institute (NCI), 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|