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

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00937768
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Prostate Adenocarcinoma; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage IV Prostate Cancer	Drug: Goserelin Acetate; Other: Laboratory Biomarker Analysis; Drug: Leuprolide Acetate; Other: Quality-of-Life Assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. 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:

1. 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.

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

3. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Temporary Androgen Deprivation Therapy in High Risk Prostate Cancer Following Radical Prostatectomy
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jun 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A (antihormone therapy) 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; Given SC; Other Names: ZDX Zoladex ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Leuprolide Acetate; Given IM; Other Names: 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 ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment
No Intervention: Arm B (no antihormone therapy) Patients undergo observation every 3 months for 9 months.

Outcome Measures

Primary Outcome Measures

1. Biochemical Progression-free Survival Rate [2 years]

   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

1. Number of Deaths [2 years]

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

2. Percentage of Participants With Grade 3 or Higher Adverse Events Regardless of Attribution [2 years]

   Percentage of Participants with Grade 3 or Higher Adverse Events regardless of attribution per NCI CTCAE Version 3

3. Average Overall FACT-P Total Score at Baseline, Months 3 and 6 [Baseline and 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.

4. Average LASA Overall Quality of Life at Baseline, Months 3 and 6 [Baseline to 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.

Other Outcome Measures

1. Correlation of Circulating Tumor Cells or Circulating Endothelial Cells Following Study Treatments With Biochemical Progression-free Survival Rate [2 years]

2. Evaluation of Prognostic and Predictive Tissue Based Biomarkers (CTCs, CECs) [2 years]

3. Measurements of Serum and Urine Biomarkers, and Comparison Between the Two Arms [2 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Robert Karnes, Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00937768
• Other Study ID Numbers: MC0852; NCI-2009-01147; 08-001519; MC0852; P30CA015083
• First Posted: Jul 13, 2009
• Last Update Posted: Dec 27, 2019
• Last Verified: Dec 1, 2018

• Additional relevant MeSH terms: Prostatic Neoplasms; Leuprolide; Goserelin

Study Results

Participant Flow

Recruitment Details	Sixteen (16) participants were recruited at Mayo Clinic (Rochester) between July 2009 and June 2012.
Pre-assignment Detail	This trial was terminated early due to funding issues.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Period Title: Overall Study
STARTED	8	8
COMPLETED	0	0
NOT COMPLETED	8	8

Baseline Characteristics

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy	Total
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.	Total of all reporting groups
Overall Participants	8	8	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (8.6)	62.8 (7.4)	62.0 (7.8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	8 100%	8 100%	16 100%
Region of Enrollment (participants) [Number]
United States	8 100%	8 100%	16 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

No participants reached the 2 years follow up due to the early termination of the trial.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	0	0

2. Secondary Outcome

Title	Number of Deaths
Description	The number of deaths due to any cause are reported below.
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Study terminated prematurely due to funding issues. Planned analysis for Overall Survival and Prostate Cancer Specific Survival was not performed due to the nature of the closure. Thus, the number of deaths are reported below.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	8	8
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	8	8
Number [percentage of patients]	100	37.5

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients who completed the FACT-P and had FACT-P Total Score data at each of the time points are included in each analysis at each time point below.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	7	7
Baseline	122.7 (5.9)	114.8 (16.92)
Month 3	118.6 (19.11)	117.8 (18.67)
Month 6	109.4 (23.83)	136.8 (3.43)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Patients who completed the LASA and had LASA Overall Quality of Life data at each of the time points are included in each analysis at each time point below.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	7	7
Baseline	8.8 (0.75)	6.9 (1.77)
Month 3	1.0 (1.63)	7.0 (1.22)
Month 6	6.2 (3.19)	8.7 (0.58)

6. Other Pre-specified Outcome

Title	Correlation of Circulating Tumor Cells or Circulating Endothelial Cells Following Study Treatments With Biochemical Progression-free Survival Rate
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Study terminated prematurely due to funding issues. Planned analysis was not performed due to the nature of the closure.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	0	0

7. Other Pre-specified Outcome

Title	Evaluation of Prognostic and Predictive Tissue Based Biomarkers (CTCs, CECs)
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Study terminated prematurely due to funding issues. Planned analysis was not performed due to the nature of the closure.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	0	0

8. Other Pre-specified Outcome

Title	Measurements of Serum and Urine Biomarkers, and Comparison Between the Two Arms
Time Frame	2 years

Outcome Measure Data

Analysis Population Description

Study terminated prematurely due to funding issues. Planned analysis was not performed due to the nature of the closure.

Arm/Group Title	Androgen Deprivation Therapy	No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.	Patients undergo observation every 3 months for 9 months.
Measure Participants	0	0

Adverse Events

Arm/Group Title	Androgen Deprivation Therapy		No Androgen Deprivation Therapy
Arm/Group Description	Patients receive leuprolide acetate intramuscularly (IM) on day 1 OR goserelin acetate subcutaneously (SC) on day 1.		Patients undergo observation every 3 months for 9 months.
All Cause Mortality
	Androgen Deprivation Therapy		No Androgen Deprivation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)
Serious Adverse Events
	Androgen Deprivation Therapy		No Androgen Deprivation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		1/8 (12.5%)
Renal and urinary disorders
Urinary retention	0/8 (0%)	0	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Androgen Deprivation Therapy		No Androgen Deprivation Therapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/8 (100%)		6/8 (75%)
Gastrointestinal disorders
Diarrhea	1/8 (12.5%)	1	1/8 (12.5%)	2
General disorders
Fatigue	5/8 (62.5%)	12	3/8 (37.5%)	3
Musculoskeletal and connective tissue disorders
Bone pain	5/8 (62.5%)	17	1/8 (12.5%)	7
Myalgia	5/8 (62.5%)	9	2/8 (25%)	2
Nervous system disorders
Dizziness	2/8 (25%)	3	1/8 (12.5%)	1
Taste alteration	2/8 (25%)	3	1/8 (12.5%)	1
Psychiatric disorders
Libido decreased	8/8 (100%)	26	3/8 (37.5%)	3
Renal and urinary disorders
Urinary frequency	7/8 (87.5%)	15	5/8 (62.5%)	6
Urinary retention	7/8 (87.5%)	13	5/8 (62.5%)	16
Reproductive system and breast disorders
Erectile dysfunction	8/8 (100%)	31	6/8 (75%)	15
Gynecomastia	2/8 (25%)	4	0/8 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/8 (37.5%)	6	0/8 (0%)	0
Skin and subcutaneous tissue disorders
Rash acneiform	3/8 (37.5%)	10	1/8 (12.5%)	1
Sweating	4/8 (50%)	9	2/8 (25%)	2
Vascular disorders
Flushing	3/8 (37.5%)	4	0/8 (0%)	0
Hot flashes	7/8 (87.5%)	21	1/8 (12.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.