Back to resultsSWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer
Primary Purpose
Prostate Cancer
Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
bicalutamide
goserelin acetate
clinical observation
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
Eligibility Criteria
DISEASE CHARACTERISTICS: Histologically or cytologically confirmed adenocarcinoma of the prostate Metastatic stage IV (stage D2) Any number of bone metastases by bone scan allowed Unequivocal visceral organ metastases (liver, brain, or lung) allowed No suspected second primary tumors unless metastases are histologically confirmed, including special stains (e.g., prostate specific antigen [PSA] and prostatic alkaline phosphatase [PAP]) For entry into late induction therapy: No more than 1 month from the beginning of antiandrogen therapy to the beginning of luteinizing hormone-releasing hormone (LHRH) agonist therapy No more than 6 months since initiation of current combined androgen-deprivation therapy (LHRH agonist and antiandrogen) The effectiveness of the current depot LHRH agonist would not extend beyond 8 months after initiation of combined androgen therapy PSA at least 5 ng/mL No acute spinal cord compression PATIENT CHARACTERISTICS: Age: Adult Performance status: SWOG 0-2 Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Recovered from any major infection No active medical illness that would preclude study or limit survival No other malignancy within the past 5 years except: Adequately treated basal cell or squamous cell skin cancer Adequately treated carcinoma in situ of the bladder Adequately treated other superficial cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent biological response modifier therapy Chemotherapy: No concurrent chemotherapy Endocrine therapy: See Disease Characteristics More than 1 year since any prior neoadjuvant or adjuvant hormonal therapy for a duration of no more than 4 months Single or combination therapy allowed More than 1 year since prior finasteride for prostate cancer for a duration of no more than 9 months (less than 6 months for benign prostatic hypertrophy) Prior or concurrent megestrol for hot flashes allowed No other concurrent hormonal therapy Radiotherapy: No concurrent radiotherapy other than palliation of painful bone metastases Surgery: No prior bilateral orchiectomy Recovered from any prior major surgery
Sites / Locations
- Tom Baker Cancer Centre - Calgary
- Cross Cancer Institute at University of Alberta
- University of British Columbia
- Nova Scotia Cancer Centre
- Cancer Centre of Southeastern Ontario at Kingston General Hospital
- London Regional Cancer Program at London Health Sciences Centre
- Ottawa Hospital Regional Cancer Centre - General Campus
- Odette Cancer Centre at Sunnybrook
- Princess Margaret Hospital
- Hopital Notre-Dame du CHUM
- McGill Cancer Centre at McGill University
- Centre Hospitalier Universitaire de Quebec
- CHUS-Hopital Fleurimont
- Saskatoon Cancer Centre at the University of Saskatchewan
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Consolidation arm I
Consolidation arm II
Arm Description
Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression.
Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy.
Outcomes
Primary Outcome Measures
Overall Survival
Non-inferiority test to determine if intermittent combined androgen deprivation (CAD) overall survival is not substantially worse than continuous CAD overall survival. Specifically, the trial is designed for a one-sided test of the hypothesis that the hazard ratio of intermittent CAD to continuous CAD is 1.2. The assumptions used to compute the trial size are an overall type I error rate of 0.05 and a type II error of 0.10 (power = 0.9).
Physical Functioning as Measured by the SF-36
This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months
Emotional Functioning as Measured by the SF-36 Mental Health Inventory
This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months
Erectile Dysfunction
This outcome was assessed by having patients report whether they had erectile dysfunction (a score of 1) or no erectile dysfunction (a score of 0). This analysis looks at change from Baseline to 3 Months.
High Libido
This outcome was assessed by having patients report whether their interest in sexual activities was very high, high, or moderate (a score of 1) or low or very low (a score of 0). This outcome measure is reporting a change from baseline in the percentage of participants with High Libido at 3 months. "High Libido" is defined as very high, high or moderate interest in sexual activities.
Vitality
This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. This analysis looks at mean change from Baseline score to 3 Months.
Secondary Outcome Measures
Full Information
NCT ID
NCT00002651
First Posted
November 1, 1999
Last Updated
March 3, 2017
Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI), NCIC Clinical Trials Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, European Organisation for Research and Treatment of Cancer - EORTC
1. Study Identification
Unique Protocol Identification Number
NCT00002651
Brief Title
SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer
Official Title
Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
May 1995 (undefined)
Primary Completion Date
June 2013 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
SWOG Cancer Research Network
Collaborators
National Cancer Institute (NCI), NCIC Clinical Trials Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, European Organisation for Research and Treatment of Cancer - EORTC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
RATIONALE: Testosterone can stimulate the growth of prostate cancer cells. Hormone therapy may be effective treatment for prostate cancer. It is not yet known which regimen of hormone therapy is most effective for stage IV prostate cancer.
PURPOSE: This randomized phase III trial is studying two different regimens of hormone therapy and comparing how well they work in treating men with stage IV prostate cancer.
Detailed Description
OBJECTIVES:
Primary
Compare the survival of patients with metastatic stage IV prostate cancer responsive to combined androgen-deprivation therapy (CAD) treated with intermittent vs continuous CAD.
Compare the effects of these treatment regimens on impotence, libido, and vitality/fatigue as well as the physical and emotional well-being of these patients.
Secondary
Compare general symptoms, role functioning, global perception of quality of life, and social functioning of patients treated with these regimens.
Assess prostate-specific antigen (PSA) levels after continuous CAD administered before randomization and evaluate PSA changes throughout randomized treatment of these patients.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to SWOG performance status (0-1 vs 2), severity of disease (minimal vs extensive), and prior hormonal therapy (neoadjuvant hormonal therapy vs finasteride vs neither).
Induction therapy: Patients receive combined androgen-deprivation (CAD) therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily for 8 courses (7 months).
Consolidation therapy: Patients are randomized to 1 of 2 consolidation regimens.
Arm I (continuous CAD therapy): Patients continue CAD therapy as in induction therapy. Treatment continues in the absence of disease progression.
Arm II (intermittent CAD therapy): Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in induction therapy. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy.
Quality of life is assessed before induction therapy, at 3 months (before consolidation therapy), and then at 9 and 15 months.
Patients are followed every 6-12 months for at least 10 years.
PROJECTED ACCRUAL: Approximately 1,500 patients will be accrued for this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3040 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Consolidation arm I
Arm Type
Active Comparator
Arm Description
Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression.
Arm Title
Consolidation arm II
Arm Type
Experimental
Arm Description
Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease. Patients with rising PSA or progressive disease begin CAD therapy as in consolidation arm I. Patients whose PSA normalizes after 8 courses return to observation. Patients whose PSA does not normalize after 8 courses continue CAD therapy.
Intervention Type
Drug
Intervention Name(s)
bicalutamide
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
goserelin acetate
Intervention Description
Given subcutaneously
Intervention Type
Other
Intervention Name(s)
clinical observation
Intervention Description
Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.
Primary Outcome Measure Information:
Title
Overall Survival
Description
Non-inferiority test to determine if intermittent combined androgen deprivation (CAD) overall survival is not substantially worse than continuous CAD overall survival. Specifically, the trial is designed for a one-sided test of the hypothesis that the hazard ratio of intermittent CAD to continuous CAD is 1.2. The assumptions used to compute the trial size are an overall type I error rate of 0.05 and a type II error of 0.10 (power = 0.9).
Time Frame
Up to 15 years
Title
Physical Functioning as Measured by the SF-36
Description
This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months
Time Frame
3 months
Title
Emotional Functioning as Measured by the SF-36 Mental Health Inventory
Description
This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. Change from Baseline in SF-36 Score at 3 Months
Time Frame
3 months
Title
Erectile Dysfunction
Description
This outcome was assessed by having patients report whether they had erectile dysfunction (a score of 1) or no erectile dysfunction (a score of 0). This analysis looks at change from Baseline to 3 Months.
Time Frame
3 months
Title
High Libido
Description
This outcome was assessed by having patients report whether their interest in sexual activities was very high, high, or moderate (a score of 1) or low or very low (a score of 0). This outcome measure is reporting a change from baseline in the percentage of participants with High Libido at 3 months. "High Libido" is defined as very high, high or moderate interest in sexual activities.
Time Frame
3 months
Title
Vitality
Description
This outcome was scored on a scale of 0 to 100, with higher scores indicating better functioning. This analysis looks at mean change from Baseline score to 3 Months.
Time Frame
3 months
Other Pre-specified Outcome Measures:
Title
Global Perception of Quality of Life
Time Frame
15 months
Title
Social Functioning
Description
Mean of the change in social functioning from randomization
Time Frame
15 months
Title
Role Functioning
Description
Mean of the change in role functioning from randomization
Time Frame
15 months
Title
General Symptoms
Time Frame
15 months
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed adenocarcinoma of the prostate
Metastatic stage IV (stage D2)
Any number of bone metastases by bone scan allowed
Unequivocal visceral organ metastases (liver, brain, or lung) allowed
No suspected second primary tumors unless metastases are histologically confirmed, including special stains (e.g., prostate specific antigen [PSA] and prostatic alkaline phosphatase [PAP])
For entry into late induction therapy:
No more than 1 month from the beginning of antiandrogen therapy to the beginning of luteinizing hormone-releasing hormone (LHRH) agonist therapy
No more than 6 months since initiation of current combined androgen-deprivation therapy (LHRH agonist and antiandrogen)
The effectiveness of the current depot LHRH agonist would not extend beyond 8 months after initiation of combined androgen therapy
PSA at least 5 ng/mL
No acute spinal cord compression
PATIENT CHARACTERISTICS:
Age:
Adult
Performance status:
SWOG 0-2
Hematopoietic:
Not specified
Hepatic:
Not specified
Renal:
Not specified
Other:
Recovered from any major infection
No active medical illness that would preclude study or limit survival
No other malignancy within the past 5 years except:
Adequately treated basal cell or squamous cell skin cancer
Adequately treated carcinoma in situ of the bladder
Adequately treated other superficial cancer
PRIOR CONCURRENT THERAPY:
Biologic therapy:
No concurrent biological response modifier therapy
Chemotherapy:
No concurrent chemotherapy
Endocrine therapy:
See Disease Characteristics
More than 1 year since any prior neoadjuvant or adjuvant hormonal therapy for a duration of no more than 4 months
Single or combination therapy allowed
More than 1 year since prior finasteride for prostate cancer for a duration of no more than 9 months (less than 6 months for benign prostatic hypertrophy)
Prior or concurrent megestrol for hot flashes allowed
No other concurrent hormonal therapy
Radiotherapy:
No concurrent radiotherapy other than palliation of painful bone metastases
Surgery:
No prior bilateral orchiectomy
Recovered from any prior major surgery
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maha Hadi A. Hussain, MD
Organizational Affiliation
University of Michigan Rogel Cancer Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Bryan J. Donnelly, MD, FRCSC, MSC
Organizational Affiliation
Tom Baker Cancer Centre - Calgary
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Eric J. Small, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
George Wilding, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Atif Akdas, MD
Organizational Affiliation
Marmara University Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Tom Baker Cancer Centre - Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
Cross Cancer Institute at University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
Nova Scotia Cancer Centre
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H 1V7
Country
Canada
Facility Name
Cancer Centre of Southeastern Ontario at Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 5P9
Country
Canada
Facility Name
London Regional Cancer Program at London Health Sciences Centre
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4L6
Country
Canada
Facility Name
Ottawa Hospital Regional Cancer Centre - General Campus
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Facility Name
Odette Cancer Centre at Sunnybrook
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Hopital Notre-Dame du CHUM
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Facility Name
McGill Cancer Centre at McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W 1S6
Country
Canada
Facility Name
Centre Hospitalier Universitaire de Quebec
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1R 2J6
Country
Canada
Facility Name
CHUS-Hopital Fleurimont
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Saskatoon Cancer Centre at the University of Saskatchewan
City
Saskatoon
State/Province
Saskatchewan
ZIP/Postal Code
S7N 4H4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
22921015
Citation
Tangen CM, Hussain MH, Higano CS, Eisenberger MA, Small EJ, Wilding G, Donnelly BJ, Schelhammer PF, Crawford ED, Vogelzang NJ, Powell IJ, Thompson IM Jr. Improved overall survival trends of men with newly diagnosed M1 prostate cancer: a SWOG phase III trial experience (S8494, S8894 and S9346). J Urol. 2012 Oct;188(4):1164-9. doi: 10.1016/j.juro.2012.06.046. Epub 2012 Aug 22.
Results Reference
background
Citation
Hussain M, Tangen CM, Higano CS, et al.: Improved overall survival (OS) of patients (pts) with new metastatic prostate cancer (pca): better efficacy or stage migration? Data from SWOG: S9346 and 8894. [Abstract] 2010 Genitourinary Cancers Symposium, March 5-7, 2010, San Francisco, California. A-30, 2010.
Results Reference
background
PubMed Identifier
19380444
Citation
Hussain M, Goldman B, Tangen C, Higano CS, Petrylak DP, Wilding G, Akdas AM, Small EJ, Donnelly BJ, Sundram SK, Burch PA, Dipaola RS, Crawford ED. Prostate-specific antigen progression predicts overall survival in patients with metastatic prostate cancer: data from Southwest Oncology Group Trials 9346 (Intergroup Study 0162) and 9916. J Clin Oncol. 2009 May 20;27(15):2450-6. doi: 10.1200/JCO.2008.19.9810. Epub 2009 Apr 20.
Results Reference
background
Citation
Goldman B, Hussain M, Tangen C, et al.: Prostate-specific antigen progression (PSA-P) as a predictor of overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): data from S9346 and S9916. [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-165, 2008.
Results Reference
background
Citation
Hussain MH, Goldman B, Tangen CM, et al.: Use of prostate-specific antigen progression (PSA-P) to predict overall survival (OS) in patients (pts) with metastatic prostate cancer (PC): data from S9346 and S9916. [Abstract] J Clin Oncol 26 (Suppl 15): A-5015, 2008.
Results Reference
background
Citation
Hussain M, Tangen CM, Higano CS, et al.: Intermittent (IAD) versus continuous androgen deprivation (CAD) in hormone sensitive metastatic prostate cancer (HSM1PC) patients (pts): results of S9346 (INT-0162), an international phase III trial. [Abstract] J Clin Oncol 30 (Suppl 15): A-4, 2012.
Results Reference
result
Citation
Moinpour C, Berry DL, Ely B, et al.: Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen deprivation in patients with hormone-sensitive metastatic prostate cancer (HSM1PC)-phase III. [Abstract] J Clin Oncol 30 (Suppl 15): A-4571, 2012.
Results Reference
result
PubMed Identifier
16921051
Citation
Hussain M, Tangen CM, Higano C, Schelhammer PF, Faulkner J, Crawford ED, Wilding G, Akdas A, Small EJ, Donnelly B, MacVicar G, Raghavan D; Southwest Oncology Group Trial 9346 (INT-0162). Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol. 2006 Aug 20;24(24):3984-90. doi: 10.1200/JCO.2006.06.4246.
Results Reference
result
Citation
Tangen CM, Hussain M, Wilding G, et al.: Determinants of prostate specific antigen (PSA) normalization in prostate cancer (PCa) patients (pts) treated with androgen deprivation (AD) on Southwest Oncology Group (SWOG) study 9346 (INT-0162). [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1591, 2003.
Results Reference
result
PubMed Identifier
26720308
Citation
Hershman DL, Unger JM, Wright JD, Ramsey S, Till C, Tangen CM, Barlow WE, Blanke C, Thompson IM, Hussain M. Adverse Health Events Following Intermittent and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer. JAMA Oncol. 2016 Apr;2(4):453-61. doi: 10.1001/jamaoncol.2015.4655.
Results Reference
derived
PubMed Identifier
25087673
Citation
Eggener S. Commentary on "Intermittent versus continuous androgen deprivation in prostate cancer." Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr, University of Michigan, Division of Hematology/Oncology, Ann Arbor, MI. N Engl J Med 2013; 368(14):1314-25. doi: 10.1056/NEJMoa1212299. Urol Oncol. 2014 Aug;32(6):936-7. doi: 10.1016/j.urolonc.2014.01.009.
Results Reference
derived
PubMed Identifier
23550669
Citation
Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013 Apr 4;368(14):1314-25. doi: 10.1056/NEJMoa1212299.
Results Reference
derived
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SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer
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