Hormone Therapy in Treating Men With Stage IV Prostate Cancer - Full Text View

Purpose

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.

Condition	Intervention	Phase
Prostate Cancer	Drug: bicalutamide Drug: goserelin acetate Other: clinical observation	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III

Resource links provided by NLM:

Genetics Home Reference related topics: prostate cancer

MedlinePlus related topics: Cancer Hormones Prostate Cancer

Drug Information available for: Goserelin Bicalutamide Goserelin acetate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Treatment-specific symptoms as measured on the four-item Medical Outcomes Study Short Form-36 (SF-36) and Vitality scale [ Designated as safety issue: No ]
Physical functioning as measured by the SF-36 [ Designated as safety issue: No ]
Emotional functioning as measured by the SF-36 Mental Health Inventory [ Designated as safety issue: No ]

Secondary Outcome Measures:

Symptoms as assessed by the Symptom Distress Scale [ Designated as safety issue: No ]
Role functioning as assessed by the Role Functioning Scale SF-20 [ Designated as safety issue: No ]
Social functioning as assessed by the General Health Survey SF-20 [ Designated as safety issue: No ]
Global quality of life (QOL) and health-related QOL [ Designated as safety issue: No ]
Comorbidity, social support, and demographic variables [ Designated as safety issue: No ]


Estimated Enrollment:	1512
Study Start Date:	May 1995
Estimated Primary Completion Date:	June 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Consolidation arm I Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression.	Drug: bicalutamide Given orally Drug: goserelin acetate Given subcutaneously
Experimental: Consolidation arm II 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.	Drug: bicalutamide Given orally Drug: goserelin acetate Given subcutaneously Other: clinical observation Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.

Arms

Assigned Interventions

Active Comparator: Consolidation arm I

Patients continue CAD therapy comprising goserelin subcutaneously once a month and oral bicalutamide once daily. Treatment continues in the absence of disease progression.

Drug: bicalutamide

Given orally

Drug: goserelin acetate

Given subcutaneously

Experimental: Consolidation arm II

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.

Drug: bicalutamide

Given orally

Drug: goserelin acetate

Given subcutaneously

Other: clinical observation

Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.

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.

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002651

Locations


Canada, Alberta
Tom Baker Cancer Centre - Calgary	Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Bryan Donnelly 403-259-2676
Cross Cancer Institute at University of Alberta	Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Peter Venner 780-432-8757
Canada, British Columbia
University of British Columbia	Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: S. Larry Goldenberg 604-875-4111
Canada, Nova Scotia
Nova Scotia Cancer Centre	Recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Contact: Derek Wilke 902-473-6022
Canada, Ontario
Cancer Centre of Southeastern Ontario at Kingston General Hospital	Recruiting
Kingston, Ontario, Canada, K7L 5P9
Contact: Aamer Mahmud 613-544-2631
London Regional Cancer Program at London Health Sciences Centre	Recruiting
London, Ontario, Canada, N6A 4L6
Contact: Joseph Chin 519-685-8451
Ottawa Hospital Regional Cancer Centre - General Campus	Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Libni Eapen 613-737-7700
Odette Cancer Centre at Sunnybrook	Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Laurence Klotz 416-480-4673
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Juanita Crook 416-946-4501
Canada, Quebec
Hopital Notre-Dame du CHUM	Recruiting
Montreal, Quebec, Canada, H2L 4M1
Contact: Fred Saad 514-890-8000
McGill Cancer Centre at McGill University	Recruiting
Montreal, Quebec, Canada, H2W 1S6
Contact: Raghu Rajan 514-934-1934
Centre Hospitalier Universitaire de Quebec	Recruiting
Quebec City, Quebec, Canada, G1R 2J6
Contact: Louis Lacombe 418-691-5O50
CHUS-Hopital Fleurimont	Recruiting
Sherbrooke, Quebec, Canada, J1H 5N4
Contact: Abdenour Nabid 819-346-1110
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan	Recruiting
Saskatoon, Saskatchewan, Canada, S7N 4H4
Contact: Donald B. Gardiner 306-655-2743

Sponsors and Collaborators

Southwest Oncology Group

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

Investigators


Study Chair:	Maha Hadi A. Hussain, MD	University of Michigan Cancer Center
Study Chair:	Bryan J. Donnelly, MD, FRCSC, MSC	Tom Baker Cancer Centre - Calgary
Study Chair:	Eric J. Small, MD	University of California, San Francisco
Study Chair:	George Wilding, MD	University of Wisconsin, Madison
OverallOfficial:	Atif Akdas, MD	Marmara University Hospital

More Information

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.


Responsible Party:	Laurence H. Baker, Southwest Oncology Group - Group Chair's Office
ClinicalTrials.gov Identifier:	NCT00002651 History of Changes
Other Study ID Numbers:	CDR0000064184 SWOG-9346 CAN-NCIC-PR8 CALGB-9594 ECOG-S9346 EORTC-30985 CAN-NCIC-JPR8 INT-0162
Study First Received:	November 1, 1999
Last Updated:	October 23, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):


adenocarcinoma of the prostate stage IV prostate cancer recurrent prostate cancer

Additional relevant MeSH terms:


Prostatic Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases, Male Prostatic Diseases Goserelin	Bicalutamide Antineoplastic Agents, Hormonal Antineoplastic Agents Androgen Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 30, 2016