Surgery With or Without Docetaxel and Leuprolide or Goserelin in Treating Patients With High-Risk Localized Prostate Cancer
- Conditions
- Prostate Cancer
- Interventions
- Registration Number
- NCT00430183
- Lead Sponsor
- Alliance for Clinical Trials in Oncology
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as goserelin and leuprolide, may stop the adrenal glands from making androgens. Giving docetaxel and leuprolide or goserelin before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether giving docetaxel and leuprolide or goserelin before surgery is more effective than surgery alone in treating patients with prostate cancer.
PURPOSE: This randomized phase III trial is studying docetaxel and leuprolide or goserelin to see how well they work when given before surgery compared with surgery alone in treating patients with high-risk localized prostate cancer.
- Detailed Description
This randomized trial tests whether the addition of chemohormonal therapy improves PSA-progression free survival in patients with high risk, clinically-localized prostate cancer. The neoadjuvant approach is taken since there appears to be a higher acceptance rate in the prostate population for this type of therapy and several phase II trials have demonstrated its safety. Multiple chemotherapeutic therapies have shown efficacy in advanced prostate cancer and docetaxel has become the community standard. Many high risk patients are initiated on LHRH agonists at or near the time of diagnosis of their prostate cancer. In order to allow the inclusion of these patients in the protocol, enhanced enrollment and maintain compliance with therapy, up to 3 months of androgen deprivation therapy prior to enrollment will be permitted. This study will therefore be able to test the hypothesis that targeting both androgen-sensitive and chemotherapy- sensitive prostate cancer cells will improve outcomes in these high-risk patients.
OUTLINE: This is a multicenter, randomized study. Patients are stratified according to nomogram-predicted biochemical progression-free survival at 5 years (0-20.9% vs 21-39.9% vs 40-59.9% vs ≥ 60%) and androgen-deprivation therapy prior to randomization ≤ 4 months (no vs yes). Patients are randomized to 1 of 2 treatment arms. Please see the Arms sections for more details.
The primary and secondary objectives are described below.
Primary:
- 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:
* 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
Patients are followed up to 15 years post-randomization.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Male
- Target Recruitment
- 788
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: docetaxel + LHRH agonist + surgical intervention LHRH agonist Patients receive six cycles of docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines. Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery. Arm A: docetaxel + LHRH agonist + surgical intervention surgery Patients receive six cycles of docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines. Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery. Arm B: surgical intervention surgery All patients undergo standard surgical intervention. The surgical procedures will be performed within 60 days of randomization. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. Adjuvant radiation must be initiated within 6 months of the date of surgery. Arm A: docetaxel + LHRH agonist + surgical intervention docetaxel Patients receive six cycles of docetaxel administered every 3 weeks combined with 18-24 weeks of androgen deprivation therapy. During each cycle of chemotherapy, all patients should undergo premedication with dexamethasone 8 mg orally prior to docetaxel. Dexamethasone may also be given intravenously according to institutional guidelines. Patients will also receive androgen deprivation for 18-24 weeks of an LHRH agonist (eg, leuprolide acetate, goserelin acetate). Additional premedication and antiemetics may be given at the physician's discretion and as defined by the protocol. Patients will undergo standard surgical intervention. The surgical procedures will be performed within 60 days of the completion of neoadjuvant therapy. Patients are allowed to receive adjuvant external beam radiation at the discretion of the treating physician and as defined per the protocol. It must be initiated within 6 months of the date of surgery.
- Primary Outcome Measures
Name Time Method Proportion of Biochemical Progression-Free Survival (bPFS Proportion) at 3 Years Up to 3 years Proportion of participants surviving 3 years from randomization without biochemical progression or death. bPFS was defined as the time from randomization to the date of the first documented biochemical progression or death. Progression will be defined as having experienced either of the following: a serum PSA level \> 0.2 ng/mL that increases on 2 consecutive occasions each of which is at least 3 months apart or death occurs. The time of biochemical failure is measured from the date of randomization to the date of the first PSA level \> 0.2 ng/mL.
- Secondary Outcome Measures
Name Time Method Prostate Cancer-specific-free Survival (The Time From Randomization to the Time of Death Due to Prostate Cancer.) Up to 15 years post-randomization Disease Progression Up to 15 years post-randomization 5-year bPFS Rate 5 years Proportion of participants surviving 5 years from randomization without biochemical progression or death.
Unacceptable Toxicity (Grade 3 or Higher Toxicity) Up to 15 years post-randomization Overall Survival (The Date of Randomization to the Time of Death Due to Prostate Cancer.) Up to 15 years post-randomization Time to Clinical Local Recurrence (The Time From Randomization to the First Biopsy-proven Recurrence in the Prostatic Bed or New Mass.) Up to 15 years post-randomization Time to Metastatic Disease Progression (The Date of Randomization to Date of Evidence of Systemic Disease on Bone Scan or Cross Sectional Imaging.) Up to 15 years post-randomization
Trial Locations
- Locations (226)
Providence Cancer Center
🇺🇸Anchorage, Alaska, United States
Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
🇺🇸Fairbanks, Alaska, United States
Alta Bates Summit Comprehensive Cancer Center
🇺🇸Berkeley, California, United States
Peninsula Medical Center
🇺🇸Burlingame, California, United States
USC/Norris Comprehensive Cancer Center and Hospital
🇺🇸Los Angeles, California, United States
Sutter Health - Western Division Cancer Research Group
🇺🇸Novato, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
Naval Medical Center - San Diego
🇺🇸San Diego, California, United States
California Pacific Medical Center - Pacific Campus
🇺🇸San Francisco, California, United States
Sutter Pacific Medical Foundation
🇺🇸Santa Rosa, California, United States
Scroll for more (216 remaining)Providence Cancer Center🇺🇸Anchorage, Alaska, United States