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

Primary Purpose

Prostate Adenocarcinoma, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Goserelin Acetate
Laboratory Biomarker Analysis
Leuprolide Acetate
Quality-of-Life Assessment
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Prostate Adenocarcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Arm A (antihormone therapy)

Arm B (no antihormone therapy)

Arm Description

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.

Patients undergo observation every 3 months for 9 months.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of Deaths
The number of deaths due to any cause are reported below.
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
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.
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.

Full Information

First Posted
July 9, 2009
Last Updated
December 9, 2019
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00937768
Brief Title
Leuprolide Acetate or Goserelin Acetate Compared With 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 Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Terminated
Study Start Date
July 2009 (undefined)
Primary Completion Date
June 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Adenocarcinoma, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer, Stage III Prostate Cancer, Stage IV Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (antihormone therapy)
Arm Type
Experimental
Arm Description
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.
Arm Title
Arm B (no antihormone therapy)
Arm Type
No Intervention
Arm Description
Patients undergo observation every 3 months for 9 months.
Intervention Type
Drug
Intervention Name(s)
Goserelin Acetate
Other Intervention Name(s)
ZDX, Zoladex
Intervention Description
Given SC
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Drug
Intervention Name(s)
Leuprolide Acetate
Other Intervention Name(s)
A-43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Procren, Procrin, Prostap, TAP-144, Trenantone, Uno-Enantone, Viadur
Intervention Description
Given IM
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Biochemical Progression-free Survival Rate
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Number of Deaths
Description
The number of deaths due to any cause are reported below.
Time Frame
2 years
Title
Percentage of Participants With Grade 3 or Higher Adverse Events Regardless of Attribution
Description
Percentage of Participants with Grade 3 or Higher Adverse Events regardless of attribution per NCI CTCAE Version 3
Time Frame
2 years
Title
Average Overall FACT-P Total Score at Baseline, Months 3 and 6
Description
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.
Time Frame
Baseline and months 3 and 6
Title
Average LASA Overall Quality of Life at Baseline, Months 3 and 6
Description
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.
Time Frame
Baseline to Months 3 and 6
Other Pre-specified Outcome Measures:
Title
Correlation of Circulating Tumor Cells or Circulating Endothelial Cells Following Study Treatments With Biochemical Progression-free Survival Rate
Time Frame
2 years
Title
Evaluation of Prognostic and Predictive Tissue Based Biomarkers (CTCs, CECs)
Time Frame
2 years
Title
Measurements of Serum and Urine Biomarkers, and Comparison Between the Two Arms
Time Frame
2 years

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Karnes
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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