Clinical trial NCT00002651: SWOG-9346, Hormone Therapy in Treating Men With Stage IV Prostate Cancer
Official title: Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage IV prostate cancer
recurrent prostate cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NCIC Clinical Trials Group
name: Cancer and Leukemia Group B
name: Eastern Cooperative Oncology Group
name: European Organisation for Research and Treatment of Cancer - EORTC
First posted: 2003-01-27
Enrollment: 3040
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 15 years
measure: Physical Functioning as Measured by the SF-36
timeFrame: 3 months
measure: Emotional Functioning as Measured by the SF-36 Mental Health Inventory
timeFrame: 3 months
measure: Erectile Dysfunction
timeFrame: 3 months
measure: High Libido
timeFrame: 3 months
measure: Vitality
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
measure: Global Perception of Quality of Life
timeFrame: 15 months
measure: Social Functioning
timeFrame: 15 months
measure: Role Functioning
timeFrame: 15 months
measure: General Symptoms
timeFrame: 15 months
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute at University of Alberta
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Halifax
country: Canada
facility: Nova Scotia Cancer Centre
state: Nova Scotia
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre at Sunnybrook
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital Notre-Dame du CHUM
state: Quebec
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
city: Quebec City
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
state: Quebec
city: Sherbrooke
country: Canada
facility: CHUS-Hopital Fleurimont
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre at the University of Saskatchewan
state: Saskatchewan
Study officials:
affiliation: University of Michigan Rogel Cancer Center
name: Maha Hadi A. Hussain, MD
role: STUDY_CHAIR
affiliation: Tom Baker Cancer Centre - Calgary
name: Bryan J. Donnelly, MD, FRCSC, MSC
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Eric J. Small, MD
role: STUDY_CHAIR
affiliation: University of Wisconsin, Madison
name: George Wilding, MD
role: STUDY_CHAIR
affiliation: Marmara University Hospital
name: Atif Akdas, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.