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
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
androgen-insensitive prostate cancer (AIPC).
- 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 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 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 AIPC 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 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) 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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
4-month progression-free survival.
No
James L Gulley, M.D.
Principal Investigator
National Cancer Institute (NCI)
United States: Federal Government
070106
NCT00450619
February 2007
November 2012
Name | Location |
---|---|
National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
Cancer Institute of New Jersey | New Brunswick, New Jersey 08901 |
University of Chicago | Chicago, Illinois 60637 |