Details
Title A randomized phase III study of neo-adjuvant docetaxel and androgen deprivation prior to radical prostatectomy versus immediate radical prostatectomy in patients with high-risk, clinically localized prostate cancer.
IRB CALGB90203
CC FLA9033
Hospital Florida Weston
Stage Stage 1, Stage 1A, Stage 1B, Stage 2, Stage 2A, Stage 2B, Stage 3, Stage 3A
Phase Phase 3
Disease Prostate
Drug Docetaxel
Description
Primary Objective
To determine whether treatment with neoadjuvant docetaxel and androgen deprivation therapy prior to radical prostatectomy will increase the rate of 3-year biochemical progression-free survival (bPFS) compared to treatment with immediate radical prostatectomy alone for high-risk prostate cancer patients.
Secondary Objectives
- To compare the 5-year bPFS rate, bPFS, disease progression, disease-free survival, and overall survival of patients randomized to the two arms of this trial.
- To determine the safety and tolerability of neoadjuvant docetaxel and androgen deprivation therapy prior to surgery for high-risk patients undergoing radical prostatectomy.
- To compare the impact of neoadjuvant docetaxel and androgen deprivation therapy on time to clinically apparent local disease recurrence and metastatic disease in high-risk patients undergoing radical prostatectomy for clinically localized prostate cancer.
- To compare the impact of neoadjuvant docetaxel and androgen deprivation therapy relative to RP on pathologic tumor stage, frequency of lymph node metastases and positive margin rates for high-risk patients undergoing radical prostatectomy for clinically localized prostate cancer.
- To determine if changes in serum testosterone levels will predict bPFS.
- To determine prospectively whether PSA doubling time (PSADT) is a surrogate endpoint for time to clinical metastases and overall survival.
Inclusion Criteria
ELIGIBILITY REQUIREMENTS
Histologic documentation
Histologic documentation of prostatic adenocarcinoma. Patients with small cell, neuroendocrine, or transitional cell carcinomas are not eligible.
All eligible patients must have a known Gleason sum based on biopsy or TURP at the time of registration.
- Clinically localized disease
Patients must have clinical stage T1-T3a and no radiographic evidence of metastatic disease as demonstrated by:
EITHER CT or MRI of the abdomen and pelvis, OR endorectal MRI of the pelvis that demonstrate no nodes > 1.5 cm.
If one or more pelvic lymph node(s) measures > 1.5 cm, a negative biopsy is required. If more than one lymph node is > 1.5 cm, the largest or most accessible node should be biopsied;
AND
Negative bone scan (with plain films and/or MRI and/or CT scan confirmation, if necessary).
Positive PET and Prostascint scans are not considered proof of metastatic disease.
Determination of high-risk status
Patients must have either:
A Kattan nomogram predicted probability of being free from biochemical progression at 5 years after surgery of < 60%. [6] See Appendix III for instructions for calculating this probability. Please note that for the purposes of the nomogram calculation, the pre-biopsy PSA value must be used.
OR
- Prostate biopsy Gleason sum ≥ 8
(NOTE: The Kattan nomogram probability must be calculated for all patients, including those eligible based on Gleason sum ≥ 8 only.)
Prior treatment
No prior treatment for prostate cancer including prior surgery (excluding TURP), pelvic lymph node dissection, radiation therapy, or chemotherapy. Patients may have received up to 4 months of androgen deprivation therapy (LHRH agonists, antiandrogens, or both) prior to being enrolled on the study.
Appropriate surgical candidates
Patients must be appropriate candidates for radical prostatectomy with an estimated life expectancy > 10 years as determined by a urologist. Evidence of underlying cardiac disease should be evaluated prior to enrollment to ensure that patients are not at high risk of cardiac complications.
Clotting history
Patients with a history of deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident or currently requiring systemic anticoagulation are eligible provided they are determined to be candidates for radical prostatectomy.
ECOG performance status: 0-2c.
Age: ≥ 18 years of age.
Required Initial Laboratory Values:
- ANC ≥ 1500/μL
- Platelet count ≥ 150,000/μL
- Creatinine ≤ 2.0 mg/dL
- Pre-registration serum PSA level ≤ 100 ng/mL
- Bilirubin ≤ Upper limit of institutional normal (ULN)*
- AST/ALT ≤ 1.5 X ULN
*For patients with Gilbert's Disease, ≤ 2.5 X ULN is allowed.
