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
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
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
- 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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Freedom from failure (FFF) (biochemical by PSA level or clinical by biopsy)
Benjamin Movsas, M.D.
Henry Ford Health System
United States: Food and Drug Administration
|Johns Hopkins University School of Medicine||Baltimore, Maryland 21205|
|Henry Ford Health System||Detroit, Michigan 48202|