Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer
- Determine the maximum tolerated dose (MTD) of neoadjuvant radiotherapy and docetaxel in
patients who are undergoing prostatectomy for high-risk localized prostate cancer.
- Determine the pathologic response rate in patients treated at the phase II dose.
- Determine the prostate-specific antigen (PSA) short-term response rate in patients
treated with this regimen.
- Determine the long-term safety of this regimen prior to radical prostatectomy in these
- Determine the clinical response to this regimen by urologic examination of these
- Determine the surgical margin status at the time of prostatectomy in patients treated
with this regimen.
- Determine the effect of this regimen, in terms of Health-Related Quality of Life by
Expanded Prostate Cancer Index Composite (EPIC) and urinary symptom scores by the
American Urological Association's measures, in these patients.
- Determine the clinical progression-free rate in patients treated with this regimen.
- Identify pretreatment predictors of response in these patients by examining tissue
biomarkers in preserved pretreatment biopsy specimens.
- Determine the biologic impact of this regimen on these patients by examining the
- Collect frozen serum for future analysis of correlative biomarkers.
- Compare the RNA content (gene expression profile) of pre- and post-treatment tumor
specimens in order to describe the molecular impact of this regimen on prostate cancer.
OUTLINE: This is a phase I, dose-escalation study of docetaxel followed by a phase II study.
All patients undergo a biopsy of the prostate to gather research-only specimens prior to the
beginning of treatment.
- Phase I: Patients undergo radiotherapy once daily, 5 days a week, for 5 weeks. Patients
also receive docetaxel IV on days 1, 8, 15, 22, and 29. Treatment continues in the
absence of disease progression or unacceptable toxicity. Approximately 4-6 weeks after
completion of chemoradiotherapy, patients undergo a radical prostatectomy.
Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience a dose-limiting toxicity. At least 6 patients are treated at the
- Phase II: Patients undergo radiotherapy as in phase I. Patients also receive docetaxel
at the MTD determined in phase I and then undergo prostatectomy as in phase I.
PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose
Between treatment groups
Mark Garzotto, MD
OHSU Knight Cancer Institute
United States: Food and Drug Administration
|Veterans Affairs Medical Center - Portland||Portland, Oregon 97207|
|OHSU Knight Cancer Institute||Portland, Oregon 97239|