NCT00583492

Randomized Trial of Suicide Gene Therapy and Prostate Cancer

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 44 (actual)
• Sponsor: Henry Ford Health System · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

OBJECTIVES 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. Primary 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). Secondary 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. Exploratory To examine: * 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.

Conditions

• Prostate Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Ad5-yCD/mutTKSR39rep-ADP	Ad5-yCD/mutTKSR39rep-ADP (1 x 10\^12 vp) on day 1 Plus Radiation - 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 Plus 2 week course (weekdays only) of 5-FC and vGCV prodrug therapy
RADIATION	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

Timeline

• Start date: 2007-12-01
• Primary completion: 2013-09-01
• Completion: 2013-09-01
• First posted: 2007-12-31
• Last updated: 2016-03-17
• Results posted: 2016-03-17

Locations

2 sites across 1 country: United States