SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer

NCT ID: NCT00002651

Last Updated: 2017-04-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 3040 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1995-05-31
• Study Completion Date: 2013-06-30

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

bicalutamide

Intervention Type: DRUG

Given orally

goserelin acetate

Intervention Type: DRUG

Given subcutaneously

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.

Group Type: EXPERIMENTAL

bicalutamide

Intervention Type: DRUG

Given orally

goserelin acetate

Intervention Type: DRUG

Given subcutaneously

clinical observation

Intervention Type: OTHER

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

Interventions

bicalutamide

Given orally

Intervention Type: DRUG

goserelin acetate

Given subcutaneously

Intervention Type: DRUG

clinical observation

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

Intervention Type: OTHER

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

NCIC Clinical Trials Group

NETWORK

Sponsor Role: collaborator

Cancer and Leukemia Group B

NETWORK

Sponsor Role: collaborator

Eastern Cooperative Oncology Group

NETWORK

Sponsor Role: collaborator

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

SWOG Cancer Research Network

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maha Hadi A. Hussain, MD

Role: STUDY_CHAIR

University of Michigan Rogel Cancer Center

Bryan J. Donnelly, MD, FRCSC, MSC

Role: STUDY_CHAIR

Tom Baker Cancer Centre - Calgary

Eric J. Small, MD

Role: STUDY_CHAIR

University of California, San Francisco

George Wilding, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Atif Akdas, MD

Role: STUDY_CHAIR

Marmara University Hospital

Locations

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, Canada

University of British Columbia

Vancouver, British Columbia, Canada

Nova Scotia Cancer Centre

Halifax, Nova Scotia, Canada

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada

Odette Cancer Centre at Sunnybrook

Toronto, Ontario, Canada

Princess Margaret Hospital

Toronto, Ontario, Canada

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, Canada

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, Canada

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 22921015 (View on PubMed)

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

PMID: 19380444 (View on PubMed)

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.

Reference Type: BACKGROUND

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.

Reference Type: BACKGROUND

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

PMID: 16921051 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 26720308 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25087673 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 23550669 (View on PubMed)

Other Identifiers

SWOG-9346

Identifier Type: -

Identifier Source: secondary_id

CAN-NCIC-PR8

Identifier Type: -

Identifier Source: secondary_id

CALGB-9594

Identifier Type: -

Identifier Source: secondary_id

ECOG-S9346

Identifier Type: -

Identifier Source: secondary_id

EORTC-30985

Identifier Type: -

Identifier Source: secondary_id

CAN-NCIC-JPR8

Identifier Type: -

Identifier Source: secondary_id

INT-0162

Identifier Type: -

Identifier Source: secondary_id

CDR0000064184

Identifier Type: -

Identifier Source: org_study_id