Randomized Trial of Suicide Gene Therapy and Prostate Cancer (ReCAP)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Controlled Trial of Replication-Competent Adenovirus-Mediated Suicide Gene Therapy in Combination With IMRT Versus IMRT Alone for the Treatment of Newly-Diagnosed Prostate Cancer With an Intermediate Risk Profile|
- Freedom from failure (FFF) (biochemical by PSA level or clinical by biopsy) [ Time Frame: 8 years ] [ Designated as safety issue: No ]
- Acute (<=90 days) and long term (>90 days) GI/GU toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
- Prostate biopsy status (12 cores) at 2 years [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Freedom from distant metastases [ Time Frame: 5 + years ] [ Designated as safety issue: No ]
- Disease-specific and overall survival [ Time Frame: 5 + years ] [ Designated as safety issue: No ]
- Quality of Life [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||December 2007|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Gene Therapy + IMRT
Gene Therapy + IMRT
Active Comparator: IMRT Alone
IMRT: 40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy
40 x 2 Gy for a total dose of 80 Gy or 44 x 1.8 Gy for a total dose of 79.2 Gy
This is a randomized, controlled trial that will test the hypothesis that replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IRMT)will improve freedom from failure (FFF) relative to 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile.
The trial contains two treatment arms:
Arm 1- Gene Therapy + IMRT Arm 2- IMRT
The study will be stratified by clinical site and pre-treatment risk factors (e.g., % positive biopsy cores, Gleason score.
- Gleason score 5/6 AND PSA <10 ng/mL; AND >=50% positive biopsy cores
- (Gleason score 5/6 and PSA 10-20 ng/mL) OR (Gleason score 7 and PSA 0 - 20 ng/mL); AND <50% positive biopsy cores
- Gleason score 5/6 and PSA 10-20 ng/mL) OR (Gleason score 7 and PSA 0-20 ng/mL) AND >=50% positive biopsy cores.
An interim safety analysis (Interim Analysis 1) will be conducted after the first 21 patients in the investigational therapy arm, and a total of 42 subjects in both arms, have completed the 90 day toxicity assessment following randomization (phase 2 component). If, at this point, there are no safety concerns as determined by the Data and Safety Monitoring Board (DSMB), the trial will continue as a phase 3 study with two additional interim analyses (Interim Analyses 2 & 3). The primary analysis for treatment efficacy will be based on all randomized subjects.
To assess the relative efficacy of replication-competent adenovirus-mediated suicide gene therapy in combination with 80 Gy intensity modulated radiotherapy (IMRT) versus 80 Gy IMRT alone in patients with newly-diagnosed prostate cancer with an intermediate-risk profile. The primary endpoint is freedom from failure (FFF) (biochemical or clinical).
To assess the difference between the two treatment arms for:
- Acute (<= 90 days) and long-term (> 90 days) toxicity.
- Prostate biopsy status (12 cores) at 2 years.
- Freedom from distant metastases.
- Disease-specific and overall survival.
- Quality of life.
- Possible effect of gene therapy on PSA doubling time (PSADT) after PSA failure.
- Possible association between the primary and secondary outcomes and Ad5-yCD/mutTKSR39rep-ADP adenovirus persistence (as measured by adenoviral DNA in blood).
- Possible association between the primary and secondary outcomes and specific immunological endpoints including levels of circulating CD4+ and CD8+ T lymphocytes, T-cell proliferation response, cytotoxic T lymphocyte (CTL) response, and development of antibodies to prostate-specific antigens.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00583492
|United States, Maryland|
|Johns Hopkins University School of Medicine|
|Baltimore, Maryland, United States, 21231|
|United States, Michigan|
|Henry Ford Health System|
|Detroit, Michigan, United States, 48202|
|Principal Investigator:||Benjamin Movsas, M.D.||Henry Ford Health System|