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

NCT00002651 | Completed Phase 3 Results DMC

• 8 other identifiers: CDR0000064184SWOG-9346CAN-NCIC-PR8CALGB-9594ECOG-S9346EORTC-30985CAN-NCIC-JPR8INT-0162
• Study Type: interventional
• Target: 3,040
• Locations: 1 country
• Sites: 14

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.

Conditions

Prostate Cancer

Keywords

adenocarcinoma of the prostate; stage IV prostate cancer; recurrent prostate cancer

Outcome Measures

Primary Outcomes (6)

• Overall Survival

  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).

  Up to 15 years

• Physical Functioning as Measured by the SF-36

  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 months

• Emotional Functioning as Measured by the SF-36 Mental Health Inventory

  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 months

• Erectile Dysfunction

  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.

  3 months

• High Libido

  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.

  3 months

• Vitality

  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.

  3 months

Other Outcomes (4)

• Global Perception of Quality of Life

  15 months

• Social Functioning

  15 months

• Role Functioning

  15 months

Study Arms (2)

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; Drug: goserelin acetate

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; Drug: goserelin acetate; Other: clinical observation

Interventions

bicalutamide DRUG

Given orally

Consolidation arm I; Consolidation arm II

goserelin acetate DRUG

Given subcutaneously

Consolidation arm I; Consolidation arm II

clinical observation OTHER

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

Consolidation arm II

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator
• NCIC Clinical Trials Group: collaborator
• Cancer and Leukemia Group B: collaborator
• Eastern Cooperative Oncology Group: collaborator
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator

Study Sites (14)

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute at University of Alberta

Edmonton, Alberta, T6G 1Z2, Canada

Location

University of British Columbia

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Nova Scotia Cancer Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Cancer Centre of Southeastern Ontario at Kingston General Hospital

Kingston, Ontario, K7L 5P9, Canada

Location

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

Ottawa Hospital Regional Cancer Centre - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Odette Cancer Centre at Sunnybrook

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Centre Hospitalier Universitaire de Quebec

Québec, Quebec, G1R 2J6, Canada

Location

CHUS-Hopital Fleurimont

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Saskatoon Cancer Centre at the University of Saskatchewan

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (12)

• 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.

  PMID: 22921015 BACKGROUND

• 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.

  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.

  PMID: 19380444 BACKGROUND

• 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.

  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.

  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.

  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.

  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.

  PMID: 16921051 RESULT

• 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.

  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.

  PMID: 26720308 DERIVED

• 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.

  PMID: 25087673 DERIVED

• 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.

  PMID: 23550669 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

bicalutamide; Goserelin; Watchful Waiting

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Outcome Assessment, Health Care; Outcome and Process Assessment, Health Care; Quality of Health Care; Health Services Administration

Results Point of Contact

• Title: Study Statistician
• Organization: SWOG Statistical Center

206-667-4623

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 27, 2003
• Study Start: May 1, 1995
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: April 17, 2017
• Results First Posted: April 17, 2017

Record last verified: 2017-03

Locations

CA (14)