153Sm-EDTMP With or Without a PSA/TRICOM Vaccine To Treat Men With Androgen-Insensitive Prostate Cancer

Prostate Cancer Clinical Trial

Official title: A Randomized Phase 2.5 Study of (153)Sm-EDTMP (Quadramet) With or Without a PSA/TRICOM Vaccine in Men With Androgen-Insensitive Metastatic Prostate Cancer

Status Completed

Clinical Trial Summary

Background:

• No treatment is known to improve survival for prostate cancer patients who have not been helped by previous treatments with hormones and chemotherapy.

• An experimental vaccine called prostate specific antigen (PSA)/TRICOM contains genes for a protein produced by prostate cancer cells called prostate-specific antigen (PSA). The vaccine can trigger the immune system to make cells that may be able to recognize and attack the cancer cells that make PSA.

• Granulocyte macrophage colony stimulating factor (GM-CSF) is an approved drug that is usually given to increase a patient's white blood cell count or to stimulate the immune system.

• 1Samarium-153-ethylene diamine tetramethylene phosphonate (53Sm-EDTMP) is a radioactive drug that has been approved for many years to treat advanced prostate cancer. It is given through a vein and can be targeted directly to tumors in the bone where it can relieve pain caused by bone lesions. Radiation also increases the level of certain proteins inside the tumor, making it easier for the immune system to find and kill the tumor cells.

• When laboratory mice were given just vaccine, just radiation, or a combination of both, the combination was most effective in treating tumors.

Objectives:

-To determine if combined treatment with PSA/TRICOM vaccine and 153Sm-EDTMP radiation can delay progression of prostate cancer better than radiation alone.

Eligibility:

-Patients who have advanced prostate cancer that has worsened despite treatments with hormones, have two or more bone lesions related to their prostate cancer, and have had prior treatment with docetaxel chemotherapy.

Design:

• Patients are randomly assigned to receive radiation alone (Arm A) or radiation with vaccine and sargramostim (Arm B).

• Arm A receives 153Sm-EDTMP radiation starting on study day 8 and repeated every 12 weeks.

• Arm B receives a priming vaccine on study day 1 and radiation on day 8. Radiation therapy is repeated every 12 weeks. Boosting vaccines are given on days 15 and 29 and then monthly. GM-CSF is given with each vaccination (on the day of the vaccination and for the next 3 days) to enhance the immune response. Vaccinations and GM-CSF are given as injections under the skin, usually in the thigh. Radiation therapy is given through a vein.

• Patients are monitored regularly with physical examinations, blood and urine tests, and scans to evaluate safety and treatment response.

• Patients who are human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2)-positive undergo apheresis, a procedure similar to donating blood, for obtaining immune cells called lymphocytes to measure the immune response to the vaccine.

Clinical Trial Description

Background

• There are no standard therapy options shown to prolong survival for patients with progressive disease on first-line docetaxel-based regimens for men with metastatic castration resistant prostate cancer (CRPC).

• Ninety percent of men in this population have bone metastasis.

• PSA/TRICOM vaccines as single agents can induce generation of PSA-specific T cells in the majority of patients and objective responses and PSA declines in a minority of patients. Furthermore, the generation of at least a 6-fold increase in PSA-specific T cells was significantly correlated with evidence of clinical benefit.

• Radiation can alter the phenotype of tumor cells (increase Fas, increase major histocompatibility complex (MHC), increase tumor-associated molecules and increase ICAM), making them much more amenable to immune-mediated killing.

• (153)Sm EDTMP is a beta emitter (with some gamma emissions) that targets osteoblastic bone lesions (such as those found in prostate cancer).

• (153)Sm EDTMP, at Food And Drug Administration (FDA)-approved doses used clinically for palliation of prostate cancer, can cause phenotypic changes in tumor cells, leading to improved killing of those cells in a cytotoxic T-cell assay in vitro.

• The combination of vaccine and radiation greatly increases antitumor efficacy in a murine subcutaneous tumor model.

Objectives

• Primary-A comparison of progression-free survival at 4 months between Arm A (153)Sm EDTMP alone) and Arm B (153Sm EDTMP with vaccine).

• Secondary-Objective responses, PSA outcomes, immunologic responses, toxicity, palliation and overall survival.

Eligibility

• Patients with metastatic CRPC who have 2 or more bone lesions consistent with prostate cancer and who have been treated with a docetaxel-based regimen.

• Patients with symptomatic soft tissue disease or parenchymal disease will be excluded.

Design

• Randomized phase 2.5 study.

• Sixty-eight patients to be enrolled and randomized to:

• Arm A: (153)Sm-EDTMP: 1 mCi/kg intravenous (IV) over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery.

Arm B: PROSTAC-V/TRICOM (vaccinia) 2 x 10^8 plaque forming unit (pfu) subcutaneously on day 1.

• (153)Sm-EDTMP: 1 mCi/kg IV over one minute on day 8. (153)Sm-EDTMP will be repeated every 12 weeks if there is adequate hematologic recovery. PROSTVAC-F/TRICOM (fowlpox) 1 x 10^9 pfu subcutaneously on days 15, 29, and then every 4 weeks. ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

• NCT number: NCT00450619
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: February 2007
• Completion date: November 2012