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

Official Title: “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”

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.

OBJECTIVES:

Primary - Compare the rate of 3-year biochemical progression-free survival (bPFS) in patients with high-risk, clinically localized prostate cancer treated with radical prostatectomy with vs without neoadjuvant chemohormonal therapy comprising docetaxel and androgen-deprivation therapy with leuprolide acetate or goserelin.

Secondary - Compare the 5-year bPFS rate, bPFS, disease progression, disease-free survival, and overall survival of patients treated with these regimens. - Determine the safety and tolerability of neoadjuvant docetaxel and androgen-deprivation therapy in these patients. - Compare the time to clinically apparent local disease recurrence and metastatic disease in patients treated with these regimens. - Compare pathologic tumor stage, frequency of lymph node metastases, and positive margin rates in patients treated with these regimens. - Determine if changes in serum testosterone levels will predict bPFS in these patients. - Determine, prospectively, whether prostate-specific antigen doubling time is a surrogate endpoint for time to clinical metastases and overall survival in these 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 in the past 3 months (no vs yes).

Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive goserelin subcutaneously or leuprolide acetate intramuscularly once every 4 or 12 weeks for 18-24 weeks (measured from the date of starting docetaxel). They also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 3 weeks for up to 6 courses. Within 60 days after completion of chemohormonal therapy, patients undergo radical prostatectomy with staging pelvic lymphadenectomy. - Arm II: Within 60 days after randomization, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.

After completion of study therapy, patients are followed at 1 and 3 months and then periodically for up to 15 years.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Drug: docetaxel
  • Given IV over 1 hour
• Drug: goserelin acetate
  • Given subcutaneously
• Drug: leuprolide acetate
  • Given intramuscularly
• Procedure: conventional surgery
  • Patients undergo radical prostatectomy with staging pelvic lymphadenectomy

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Arm I
  • Patients receive goserelin subcutaneously or leuprolide acetate intramuscularly once every 4 or 12 weeks for 18-24 weeks (measured from the date of starting docetaxel). They also receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 3 weeks for up to 6 courses. Within 60 days after completion of chemohormonal therapy, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.
• Active Comparator: Arm II
  • Within 60 days after randomization, patients undergo radical prostatectomy with staging pelvic lymphadenectomy.

Primary Measures

• 3-year biochemical progression-free survival (bPFS) rate
  • Safety Issue?: No

Secondary Measures

• 5-year bPFS rate and bPFS
  • Safety Issue?: No
• Time to clinical local recurrence
  • Safety Issue?: No
• Time to metastatic disease progression
  • Safety Issue?: No
• Unacceptable toxicity
  • Safety Issue?: Yes
• Prostate cancer-specific-free survival
  • Safety Issue?: No
• Disease progression
  • Safety Issue?: No
• Overall survival
  • Safety Issue?: No
• Death
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the prostate
• No small cell, neuroendocrine, or transitional cell carcinoma
• Clinically localized, stage T1-3a disease
• No radiographic evidence of metastatic disease*, as demonstrated by all of the following:
• No pelvic lymph nodes > 1.5 cm by CT scan or MRI of the abdomen and pelvis or endorectal MRI of the pelvis
• A negative biopsy required for lymph node(s) that measure > 1.5 cm
• If > 1 lymph node is > 1.5 cm, the largest or most accessible node is biopsied
• Negative bone scan with plain films and/or MRI/CT scan confirmation, if necessary NOTE: *Positive positron emission tomography scan and Prostascint scans are not considered proof of metastatic disease
• Serum prostate-specific antigen level ≤ 100 ng/mL within the past 6 weeks
• Patients must have a known Gleason sum based on biopsy or TURP at study entry
• High-risk disease, meeting 1 of the following criteria:
• Probability of biochemical progression-free survival at 5 years after surgery <
• 60% by Kattan nomogram prediction
• Biopsy Gleason score 8 to 10
• Deemed an appropriate candidate for radical prostatectomy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 10 years
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 150,000/mm^3
• Creatinine ≤ 2.0 mg/dL
• Bilirubin normal (≤ 2.5 times upper limit of normal [ULN] for patients with Gilbert's disease)
• AST and ALT ≤ 1.5 times ULN
• Fertile patients must use effective contraception during and for ≥ 2 months after completion of study treatment
• Not at high risk for cardiac complications
• Prior deep venous thrombosis, pulmonary embolism, and/or cerebrovascular accident allowed

PRIOR CONCURRENT THERAPY:

• No prior treatment for prostate cancer, including surgery, pelvic lymph node dissection, radiotherapy, or chemotherapy
• Prior transurethral resection of prostate allowed
• Prior androgen-deprivation therapy (e.g., luteinizing hormone-releasing hormone agonists, antiandrogens, or both) lasting ≤ 4 months allowed
• Concurrent systemic anticoagulation allowed
• No other concurrent systemic therapy, including androgen-deprivation therapy for the treatment of the prostate cancer
• No concurrent oral antiandrogens
• No concurrent aprepitant
• No other concurrent chemotherapeutic agents except for any of the following:
• Steroids given for adrenal failure
• Hormones administered for nondisease-related conditions (e.g., insulin for diabetes)
• Intermittent use of dexamethasone as an antiemetic or as pretreatment for patients receiving docetaxel

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Cancer and Leukemia Group B Other

Overall Clinical Trial Officials and Contacts

James A. Eastham, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00430183

Study ID Number: CDR0000526353

ClinicalTrials.gov Identifier: NCT00430183

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database

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