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

Study Overview
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Brief Summary
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This randomized phase II trial studies the side effects and how well giving leuprolide acetate or goserelin acetate works compared to observation in treating patients with high-risk prostate cancer who have undergone radical prostatectomy. 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.

Detailed Description
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PRIMARY OBJECTIVES: I. To compare the difference in the biochemical progression-free survival rate (bPFS) at 2-years between immediate androgen deprivation therapy (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 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 Functional Assessment of Cancer Therapy-Prostate (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: Patients are randomized to 1 of 2 treatment arms. ARM A: Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1. Courses repeat every 3 months for 9 months 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 up every three months for 2 years.

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

Conditions
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Prostate Adenocarcinoma, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage IV Prostate Cancer

Intervention / Treatment
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* Drug: Goserelin Acetate
* Other: Laboratory Biomarker Analysis
* Drug: Leuprolide Acetate
* Other: Quality-of-Life Assessment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PRE-REGISTRATION: Informed consent explained and signed prior to any study related procedures Patients with any one of the following high risk criteria: Clinical or pathological Gleason score 8-10 Prostate-specific antigen (PSA) > 20 ng/ml at initial presentation prior to radical prostatectomy Willingness to provide mandatory tissue for research purposes Willingness to provide mandatory blood for research purposes Has no history of androgen deprivation therapy within the past 6 months or has been treated neoadjuvantly up to 6 months prior to radical prostatectomy with the following agents; luteinizing hormone-releasing hormone (LHRH) agonists, anti-androgens, 5 alpha-reductase inhibitors, and peripheral anti-androgens REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; or Karnofsky performance of > 60% Patients with any one of the following high risk criteria: Gleason, prostate specific antigen, seminal vesicle and margin status (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) 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 Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 2 x institutional upper limit of normal (ULN) Total bilirubin =< 2 x institutional ULN 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 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 reconfirmed post radical prostatectomy; these patient groups may choose to register prior to or after prostatectomy Study randomization must occur =< 28 days of radical prostatectomy; all patients consented on the trial, whether consented in the pre-prostatectomy or post-prostatectomy period, will be randomized to study treatments =< 28 days of prostatectomy Ability to complete questionnaire(s) by themselves or with assistance Exclusion Criteria: PRE-REGISTRATION Transitional cell, small cell, or squamous cell carcinoma of the prostate; NOTE: 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 History of primary prostate cancer treatment Evidence of clinical nodal disease (N1) or grossly evident metastasis at the time of enrollment History of bilateral orchiectomy; unilateral orchiectomy with normal range serum testosterone levels will be allowed for enrollment 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, computed tomography (CT) and/or magnetic resonance (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; 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 Receiving other experimental drugs =< 4 weeks prior to consenting Uncontrolled infection History of other cancer, excluding squamous cell and basal cell skin cancers, within the preceding 2 years Documented history of human immunodeficiency virus (HIV) positivity or other acquired immunodeficiency disorder, congenital immunodeficiency disorder, or history of organ transplantation 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 Unable to follow up every three months for the first year to Mayo Clinic, Rochester for receiving LHRH analogues or study monitoring

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (antihormone therapy)<br>Patients receive leuprolide acetate IM on day 1 OR goserelin acetate SC on day 1. Courses repeat every 3 months for 9 months in the absence of disease progression or unacceptable toxicity. | Drug: Goserelin Acetate<br>* Given SC<br>* Other names: Zoladex;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Leuprolide Acetate<br>* Given IM<br>* Other names: Viadur;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;|
| No Intervention: Arm B (no antihormone therapy)<br>Patients undergo observation every 3 months for 9 months. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Progression-free Survival Rate | Biochemical progression-free survival (BPFS) was defined as the time from randomization to the time of biochemical progression. If a patient dies without a documentation of biochemical progression, the patient will be considered to have had progressed at the time of death. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Deaths | The number of deaths due to any cause are reported below. | 2 years | 
| Percentage of Participants With Grade 3 or Higher Adverse Events Regardless of Attribution | Percentage of Participants with Grade 3 or Higher Adverse Events regardless of attribution per NCI CTCAE Version 3 | 2 years | 
| Average Overall FACT-P Total Score at Baseline, Months 3 and 6 | The overall FACT-P Total Score at Baseline and months 3 and 6 mean and standard deviations are reported below. The FACT-P is a multidimensional, self-reported quality of life instrument consisting of 27 core items that assess participant function in 4 domains: physical, social/family, emotional, functional well-being, and supplemented by 12 site-specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert-type scale, and then combined to produce subscale scores for each domain, as well as a global quality of life score which is the sum of all 5 domain scores and ranges from 0 to 156 where higher scores represent better quality of life. | Baseline and months 3 and 6 | 
| Average LASA Overall Quality of Life at Baseline, Months 3 and 6 | LASA Overall Quality of Life at Baseline, Months 3 and 6. Quality of Life (QOL) was measured using the single-item Linear Analogue Self Assessment (LASA) on a 0-10 scale, with 0=as bad as it can be and 10=as good as it can be. The average and standard deviation of the LASA overall quality of life score are reported below at baseline, months 3 and 6. | Baseline to Months 3 and 6 |