Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Hormone Therapy in Treating Men With Stage IV Prostate Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed Adult NCI SWOG-9346 SWOG-9346, CAN-NCIC-PR8, CALGB-9594, ECOG-S9346, EORTC-30985, CAN-NCIC-JPR8, INT-0162, NCT00002651, PR8

Objectives

Primary

1. Compare the survival of patients with metastatic stage IV prostate cancer responsive to combined androgen-deprivation therapy (CAD) treated with intermittent vs continuous CAD.
2. 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

1. Compare general symptoms, role functioning, global perception of quality of life, and social functioning of patients treated with these regimens.
2. Assess prostate-specific antigen (PSA) levels after continuous CAD administered before randomization and evaluate PSA changes throughout randomized treatment of these patients.

Entry 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

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

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

Expected Enrollment

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

Outcomes

Treatment-specific symptoms as measured on the four-item Medical Outcomes Study Short Form-36 (SF-36) and Vitality scale
Physical functioning as measured by the SF-36
Emotional functioning as measured by the SF-36 Mental Health Inventory

Symptoms as assessed by the Symptom Distress Scale
Role functioning as assessed by the Role Functioning Scale SF-20
Social functioning as assessed by the General Health Survey SF-20
Global quality of life (QOL) and health-related QOL
Comorbidity, social support, and demographic variables

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.

Hussain M, Tangen CM, Higano C, et al.: 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 24 (24): 3984-90, 2006.[PUBMED Abstract]

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.

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.

Trial Contact Information

Trial Lead Organizations

Southwest Oncology Group

Maha Hadi Hussain, MD, Protocol chair		Ph: 734-936-8906; 800-865-1125

NCIC-Clinical Trials Group

Bryan Donnelly, MD, FRCSC, MSC, Protocol chair		Ph: 403-259-2676

Cancer and Leukemia Group B

Eric Small, MD, Protocol chair		Ph: 415-353-7095; 800-888-8664

Eastern Cooperative Oncology Group

George Wilding, MD, Protocol chair		Ph: 608-263-8610; 800-622-8922 Email: gxw@medicine.wisc.edu

European Organization for Research and Treatment of Cancer

Atif Akdas, MD, Study coordinator		Ph: 90-216-327-5050 Email: aakdas46@yahoo.com

Registry Information
Official Title		Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III
Trial Start Date		1995-05-15
Trial Completion Date		2012-06-01 (estimated)
Registered in ClinicalTrials.gov		NCT00002651
Date Submitted to PDQ		1995-04-25
Information Last Verified		2008-10-28
NCI Grant/Contract Number		CA32102