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

Sponsors and Collaborators:	Southwest Oncology Group National Cancer Institute (NCI) National Cancer Institute of Canada Cancer and Leukemia Group B Eastern Cooperative Oncology Group European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002651

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 Procedure: observation	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
Official Title:	Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Goserelin Bicalutamide

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 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Consolidation arm I: Active Comparator 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 Given subcutaneously
Consolidation arm II: Experimental 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 Given subcutaneously Procedure: observation Patients undergo observation in the absence of rising prostate-specific antigen (PSA) or clinical symptoms of progressive disease.

Arms

Assigned Interventions

Consolidation arm I: Active Comparator

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

Given subcutaneously

Consolidation arm II: Experimental

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

Given subcutaneously

Procedure: 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 months.

PROJECTED ACCRUAL: Approximately 1,500 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
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

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

Locations

Canada, Alberta
Cross Cancer Institute at University of Alberta	Recruiting
Edmonton, Alberta, Canada, T6G 1Z2
Contact: Peter Venner 780-432-8757
Tom Baker Cancer Centre - Calgary	Recruiting
Calgary, Alberta, Canada, T2N 4N2
Contact: Bryan Donnelly 403-259-2676
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
Edmond Odette Cancer Centre at Sunnybrook	Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Laurence Klotz 416-480-4673
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
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Juanita Crook 416-946-4501
Canada, Quebec
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
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
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)

National Cancer Institute of Canada

Cancer and Leukemia Group B

Eastern Cooperative Oncology Group

European Organization for Research and Treatment of Cancer

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	UCSF Helen Diller Family Comprehensive Cancer Center
Study Chair:	George Wilding, MD	University of Wisconsin, Madison
Investigator:	Atif Akdas, MD	Marmara University Hospital

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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.

Hussain M, Tangen CM, Schellhammer PF, et al.: Absolute PSA value after androgen deprivation (AD) is a strong independent predictor of survival in new metastatic (D2) prostate cancer (PCa): data from Southwest Oncology Group trial 9346 (INT-0162). [Abstract] J Clin Oncol 24 (Suppl 18): A-4517, 2006.

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.

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 Apr 20; [Epub ahead of print]

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.

Responsible Party:	Southwest Oncology Group - Group Chair's Office ( Laurence H. Baker )
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:	April 29, 2009
ClinicalTrials.gov Identifier:	NCT00002651 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer

Study placed in the following topic categories:

Genital Neoplasms, Male
Prostatic Diseases
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Goserelin
Urogenital Neoplasms
Genital Diseases, Male

Hormones
Recurrence
Androgen Antagonists
Bicalutamide
Adenocarcinoma
Prostatic Neoplasms
Androgens

Additional relevant MeSH terms:

Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Urogenital Neoplasms
Genital Diseases, Male

Pharmacologic Actions
Neoplasms
Androgen Antagonists
Neoplasms by Site
Therapeutic Uses
Bicalutamide
Prostatic Neoplasms

ClinicalTrials.gov processed this record on July 02, 2009