Surgery With or Without Docetaxel and Leuprolide or Goserelin in Treating Patients With High-Risk Localized Prostate Cancer

Tracking Information
First Submitted Date ICMJE	January 30, 2007
First Posted Date ICMJE	February 1, 2007
Last Update Posted Date	June 27, 2017
Study Start Date ICMJE	December 2006
Estimated Primary Completion Date	June 2018 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 13, 2015)	3-year biochemical progression-free survival (bPFS) rate [ Time Frame: 3 years ]
Original Primary Outcome Measures ICMJE; (submitted: January 30, 2007)	3-year biochemical progression-free survival rate (bPFS)
Change History	Complete list of historical versions of study NCT00430183 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 13, 2015)	5-year bPFS rate and bPFS [ Time Frame: 5 years ]; Time to clinical local recurrence (The time from randomization to the first biopsy-proven recurrence in the prostatic bed or new mass.) [ Time Frame: 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.) [ Time Frame: Up to 15 years post-randomization ]; Unacceptable toxicity (grade 3 or higher toxicity) [ Time Frame: Up to 15 years post-randomization ]; Prostate cancer-specific-free survival (The time from randomization to the time of death due to prostate cancer.) [ Time Frame: Up to 15 years post-randomization ]; Disease progression [ Time Frame: Up to 15 years post-randomization ]; Overall survival (The date of randomization to the time of death due to prostate cancer.) [ Time Frame: Up to 15 years post-randomization ]
Original Secondary Outcome Measures ICMJE; (submitted: January 30, 2007)	5-year bPFS rate and bPFS; Time to clinical local recurrence; Time to metastatic disease progression; Unacceptable toxicity; Prostate cancer-specific-free survival; Disease progression; Overall survival; Death
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Surgery With or Without Docetaxel and Leuprolide or Goserelin in Treating Patients With High-Risk Localized Prostate Cancer
Official Title ICMJE	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
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.
Study Type ICMJE	Interventional
Study Phase	Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Prostate Cancer
Intervention ICMJE	Drug: docetaxel 75 mg/m^2 will be administered intravenously over one hour on Day 1 of each cycle, every 21 days; Drug: LHRH agonist Given intramuscularly Other Names: leuprolide acetate OR goserelin acetate; Procedure: surgery Patients undergo radical prostatectomy with staging pelvic lymphadenectomy.
Study Arms	Experimental: Arm A: docetaxel + LHRH agonist + surgical intervention 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. Interventions: Drug: docetaxel Drug: LHRH agonist Procedure: surgery; Arm B: surgical intervention 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. Intervention: Procedure: surgery
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: April 13, 2016)	788
Original Enrollment ICMJE; (submitted: January 30, 2007)	750
Study Completion Date	Not Provided
Estimated Primary Completion Date	June 2018 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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%. 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: 0-2; 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 ≤ 1.5XULN (2.5XULN in patients with Gilbert's disease) AST/ALT ≤1.5XULN
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada, United States
Removed Location Countries	Peru
Administrative Information
NCT Number ICMJE	NCT00430183
Other Study ID Numbers ICMJE	CALGB 90203; U10CA031946 ( U.S. NIH Grant/Contract ); CDR0000526353 ( Other Identifier: Physician Data Query )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Alliance for Clinical Trials in Oncology
Study Sponsor ICMJE	Alliance for Clinical Trials in Oncology
Collaborators ICMJE	National Cancer Institute (NCI); Eastern Cooperative Oncology Group; NCIC Clinical Trials Group; Southwest Oncology Group
Investigators ICMJE	Study Chair: James Eastham, MD Memorial Sloan Kettering Cancer Center
PRS Account	Alliance for Clinical Trials in Oncology
Verification Date	June 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP