Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer
18 Years
N/A
Male
Prostate Cancer
Trial Information
Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer
OBJECTIVES:
Primary
- 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.
Secondary
- 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
patients.
- Determine the clinical response to this regimen by urologic examination of these
patients.
- 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
prostatectomy specimens.
- 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
MTD.
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the prostate
- Localized disease, meeting 1 of the following staging criteria:
- Clinical stage T2b (palpable bilateral movement) disease
- Surgically resectable T3 disease
- Meets any of the following high-risk* features:
- PSA ≥ 15 ng/mL
- Gleason grade ≥ 4+3 (4+3, 4+4, or 5+any, but not 3+4) NOTE: *High risk defined
as > 50% chance of failure with local therapy
- Plans to undergo prostatectomy as primary therapy
- No evidence of lymph nodes ≥ 2 cm in diameter by pelvic CT scan
- Scan only required in patients with a PSA ≥ 40 ng/mL
- No evidence of bone metastases by bone scan
PATIENT CHARACTERISTICS:
- Life expectancy ≥ 10 years
- ECOG performance status 0-2
- WBC > 3,000/mm^3
- Neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
- Direct bilirubin normal
- ALT < 2.0 times upper limit of normal (ULN) (1.5 times ULN if alkaline phosphatase
[AP] > 2.5 times ULN)
- AP < 4.0 times ULN
- No other serious medical condition that would preclude study treatment
- No other malignancy within the past 5 years except nonmelanoma skin cancer
- No peripheral neuropathy ≥ grade 2
- No hypersensitivity to drugs formulated with polysorbate 80
- No significant contraindications to corticosteroids
- No history of scleroderma
- No active inflammatory bowel disease (IBD) or IBD that is being medically treated
- Inclusion of patients with a remote history of IBD is at the discretion of
radiotherapist
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior therapy for prostate cancer, including any of the following:
- Conventional hormonal therapy (e.g., orchiectomy, luteinizing hormone-releasing
hormone therapy, antiandrogen therapy, or estrogen therapy)
- External-beam radiotherapy or brachytherapy
- Cryotherapy
- Cytotoxic chemotherapy
- No prior pelvic radiotherapy
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose
Outcome Time Frame:
Between treatment groups
Safety Issue:
Yes
Principal Investigator
Mark Garzotto, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000467219
NCT ID:
NCT00321698
Start Date:
January 2006
Completion Date:
Related Keywords:
- Prostate Cancer
- adenocarcinoma of the prostate
- stage II prostate cancer
- stage III prostate cancer
- Prostatic Neoplasms
Name | Location |
|---|---|
| Veterans Affairs Medical Center - Portland | Portland, Oregon 97207 |
| OHSU Knight Cancer Institute | Portland, Oregon 97239 |
