Summary

Eligibility
for males ages 18 years and up (full criteria)
Location
at UC Davis
Dates
study started
completion around

Description

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.

Official 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

Details

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.

Keywords

Prostate Cancer, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer, adenocarcinoma of the prostate, Prostatic Neoplasms, Docetaxel, Leuprolide, Goserelin, LHRH agonist, surgery

Eligibility

For males ages 18 years and up

  1. 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.

  2. 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.
  3. 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.)
  4. 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.

  5. 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.
  6. 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.
  7. ECOG performance status: 0-2
  8. Age: ≥ 18 years of age
  9. 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

Locations

  • University of California Davis Cancer Center
    Sacramento California 95817 United States
  • California Pacific Medical Center - Pacific Campus
    San Francisco California 94118 United States
  • Naval Medical Center - San Diego
    San Diego California 92134 United States
  • Alta Bates Summit Comprehensive Cancer Center
    Berkeley California 94704 United States
  • Peninsula Medical Center
    Burlingame California 94010 United States
  • USC/Norris Comprehensive Cancer Center and Hospital
    Los Angeles California 90089-9181 United States
  • Sutter Health - Western Division Cancer Research Group
    Novato California 94945 United States
  • Sutter Solano Medical Center
    Vallejo California 94589 United States

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Alliance for Clinical Trials in Oncology
Links
Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive
ID
NCT00430183
Phase
Phase 3 Prostate Cancer Research Study
Study Type
Interventional
Participants
About 788 people participating
Last Updated