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

• ClinicalTrials.gov Identifier: NCT00002651
• Recruitment Status: Completed
• First Posted: January 27, 2003
• Results First Posted: April 17, 2017
• Last Update Posted: April 17, 2017
• Sponsor: Southwest Oncology Group
• 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
• Information provided by (Responsible Party): Southwest Oncology Group

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: bicalutamide; Drug: goserelin acetate; Other: clinical observation	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 3040 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III
• Study Start Date: May 1995
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. Overall Survival [ Time Frame: Up to 15 years ]
   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).
2. Physical Functioning as Measured by the SF-36 [ Time Frame: 3 months ]
   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
3. Emotional Functioning as Measured by the SF-36 Mental Health Inventory [ Time Frame: 3 months ]
   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
4. Erectile Dysfunction [ Time Frame: 3 months ]
   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.
5. High Libido [ Time Frame: 3 months ]
   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.
6. Vitality [ Time Frame: 3 months ]
   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.

Other Outcome Measures:

1. Global Perception of Quality of Life [ Time Frame: 15 months ]
2. Social Functioning [ Time Frame: 15 months ]
   Mean of the change in social functioning from randomization
3. Role Functioning [ Time Frame: 15 months ]
   Mean of the change in role functioning from randomization
4. General Symptoms [ Time Frame: 15 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes 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

Locations

Canada, Alberta

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, Canada, T2N 4N2

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, Canada, T6G 1Z2

Canada, British Columbia

University of British Columbia

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Nova Scotia

Nova Scotia Cancer Centre

Halifax, Nova Scotia, Canada, B3H 1V7

Canada, Ontario

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, Canada, K7L 5P9

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, Canada, N6A 4L6

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, Canada, K1H 8L6

Odette Cancer Centre at Sunnybrook

Toronto, Ontario, Canada, M4N 3M5

Princess Margaret Hospital

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Hopital Notre-Dame du CHUM

Montreal, Quebec, Canada, H2L 4M1

McGill Cancer Centre at McGill University

Montreal, Quebec, Canada, H2W 1S6

Centre Hospitalier Universitaire de Quebec

Quebec City, Quebec, Canada, G1R 2J6

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, Canada, J1H 5N4

Canada, Saskatchewan

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, Canada, S7N 4H4

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 Rogel 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
• Study Chair: Atif Akdas, MD; Marmara University Hospital

More Information

Publications of Results:

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.

Other Publications:

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.

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.

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: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT00002651
• Other Study ID Numbers: CDR0000064184; SWOG-9346; CAN-NCIC-PR8; CALGB-9594; ECOG-S9346; EORTC-30985; CAN-NCIC-JPR8; INT-0162
• First Posted: January 27, 2003
• Results First Posted: April 17, 2017
• Last Update Posted: April 17, 2017
• Last Verified: March 2017

Keywords provided by Southwest Oncology Group:

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; Prostatic Diseases; Goserelin; Bicalutamide; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Androgen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs