Leuprolide Acetate or Goserelin Acetate Compared With Observation in Treating Patients With High-Risk Prostate Cancer Who Have Undergone Radical Prostatectomy

Condition(s) targeted: Prostate Cancer

Intervention: leuprolide acetate (Drug); goserelin (Drug); laboratory biomarker analysis (Other); quality-of-life assessment (Other); pharmacological study (Other)

Phase: Phase 2

Status: Recruiting

Sponsored by: Mayo Clinic

Official(s) and/or principal investigator(s):
Robert Karnes, M.D., Study Chair, Affiliation: Mayo Clinic

RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as goserelin acetate and leuprolide acetate, may lessen the amount of androgens made by the body and thus control prostate cancer growth. Many times, after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. However in some prostate cancers there is a chance that tumors can re-grow despite surgery based on certain high risk features.

PURPOSE: This phase II trial is studying the side effects and how well leuprolide acetate or goserelin acetate work compared to observation) in treating patients with high-risk prostate cancer who have undergone radical prostatectomy.

Official title: Phase II Trial of Temporary Androgen Deprivation Therapy in High Risk Prostate Cancer Following Radical Prostatectomy

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Biochemical progression-free survival rate

Secondary outcome:

Biochemical progression-free survival (BPFS), overall survival (OS), and prostate cancer specific survival (PCS)

Toxicity as per NCI CTCAE Version 3

Quality of life as assessed by the FACT-P and LASA tool within and between the two treatment arms

Measurements of serum and urine biomarkers, and comparison between the two arms

Correlation of circulating tumor cells or circulating endothelial cells following study treatments with biochemical progression-free survival rate

Evaluation of prognostic and predictive tissue based biomarkers (CTCs, CECs)

Detailed description: PRIMARY OBJECTIVES:

I. To compare the difference in the biochemical progression-free survival rate (bPFS) at 2-years between immediate ADT for nine months in high risk prostate cancer patients following radical prostatectomy and a similar high risk patient population followed without initiation of immediate ADT treatment.

SECONDARY OBJECTIVES:

I. To determine the three year difference in bPFS, prostate cancer specific survival, and overall survival between immediate ADT for nine months and observation for high risk prostate cancer patients following radical prostatectomy. II. To evaluate the toxicity profile and quality of life (QOL) measured by FACT-P and linear analogue self assessment (LASA) between two treatment arms.

TERTIARY OBJECTIVES:

I. To explore if serum and urine biomarker(s) levels at study entry, 9 months, or 24 months in the two treatment arms are correlated with biochemical progression-free survival rate.

II. To explore if > 5 circulating tumor cells (CTCs) or circulating endothelial cells (CECs) following study treatments are associated with biochemical progression-free survival rate.

III. To explore the prognostic and predictive value of tissue based biomarkers in high risk prostate cancer patients.

OUTLINE:

This is a randomized phase II study.

Patients are stratified according to pathological Gleason score (6-7 vs >=8) and baseline PSA at diagnosis (<10 ng/mL vs >=10 ng/mL). Patients are randomized to 1 of 2 arms.

Arm A: Patients receive leuprolide acetate intramuscularly on day 1 OR goserelin acetate subcutaneously on day 1. Treatment repeats every 3 months for a up to 3 courses in the absence of disease progression or unacceptable toxicity.

Arm B: Patients undergo observation every 3 months for 9 months. After completion of study treatment, patients are followed every three months for 2 years. PROJECTED ACCRUAL: A total of 128 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

Inclusion:

Prostate cancer patients with high-risk features may be screened for participation either prior to (pre-registration) or after (registration) radical prostatectomy

Pre-registration: Informed consent explained and signed prior to any study related procedures

Pre-registration: Patients with any one of the following "high risk" criteria: clinical or pathological Gleason score 8-10; PSA > 20 ng/mL at initial presentation prior to radical prostatectomy

Pre-registration: Willingness to provide mandatory tissue for research purposes

Pre-registration: Willingness to provide mandatory blood for research purposes

Registration: ECOG performance status of 0, 1, or 2; or Karnofsky performance of > 60%

Registration: Patients with any one of the following "high risk" criteria: GPSM score >= 10 [GS + 1*(PSA 4-10)+2*(PSA 10. 1-20)+3*(PSA>20)+2*(Seminal Vesicular or nodal involvement) +2*(margin)] (determined post radical prostatectomy)

Registration: Patients with any one of the following "high risk" criteria (continued from previous criterion): post prostatectomy seminal vesicle invasion (pT3b) or pT4; two or less microscopic lymph nodal metastasis determined at the time of prostatectomy; or Gleason 4+3 at the time of prostatectomy with margin positivity

Registration: Please contact study investigator and/or consult protocol document for specific details on laboratory criteria

Registration:

High risk patients will do one of the following:

1. for patients identified as high-risk on the basis of pathological criteria after undergoing radical prostatectomy: interval time for study enrollment after radical prostatectomy will be <= 28 days of the prostatectomy;

2. for patients identified as high-risk prior to undergoing radical prostatectomy: patients presenting with a high Gleason score (8-10) and/or a PSA >20 ng/ml are deemed eligible for study participation and study registration as long as the eligibility criteria is re-confirmed post radical prostatectomy

Registration: These patient groups may choose to register prior to or after prostatectomy

Registration: Study randomization must occur =< 28 days of radical prostatectomy

Registration: All patients consented on the trial, whether consented in the pre-prostatectomy or postprostatectomy period, will be randomized to study treatments =< 28 days of prostatectomy

Registration: Ability to complete questionnaire(s) by themselves or with assistance

Exclusion

Pre-registration: Transitional cell, small cell, or squamous cell carcinoma of the prostate

Pre-registration: Patients consented for participation prior to prostatectomy, if detected to have above listed histo-pathologies after prostatectomy will be deemed ineligible and not proceed to study randomization

Pre-registration: History of primary prostate cancer treatment

Pre-registration: Evidence of clinical nodal disease (N1) or grossly evident metastasis at the time of enrollment

Pre-registration: Androgen deprivation therapy within the past 6 months (these agents include LHRH agonists, anti-androgens, 5 alpha-reductase inhibitors, estrogens, ketoconazole, or corticosteroids or peripheral anti-androgens)

Pre-registration: History of bilateral orchiectomy

Pre-registration: Unilateral orchiectomy with normal range serum testosterone levels will be allowed for enrollment

Pre-registration: Evidence of metastasis on radiographic metastatic workup within a preceding period of 4 months from the time of study entry, including whole body radionuclide bone scan, CT and/or MR scan of the pelvis and abdomen; otherwise will perform at the time of the baseline tests and result must be normal to continue on study

Pre-registration: Results of ProstaScint or other radionuclide scans, excluding radionuclide bone scans, will NOT be used to establish metastatic disease if all other studies are negative

Pre-registration: Receiving other experimental drugs =< 4 weeks prior to consenting Pre-registration: Uncontrolled infection

Pre-registration: History of other cancer, excluding squamous cell and basal cell skin cancers, within the preceding 2 years

Pre-registration: Documented history of HIV positivity or other acquired immunodeficiency disorder, congenital immunodeficiency disorder, or history of organ transplantation

Pre-registration: Unable to follow up every three months for the first year to Mayo Clinic, Rochester for receiving LHRH analogues or study monitoring

Registration: Uncontrolled infection Registration: Unable to follow up every three months for the first year to Mayo Clinic, Rochester for receiving LHRH analogues or study monitoring

Mayo Clinic, Rochester, Minnesota 55905, United States; Recruiting
Mayo Clinic Clinical Trials Office, Phone: 507-538-7623
Robert Karnes, M.D., Principal Investigator

Starting date: October 2009
Last updated: July 18, 2011