Hormone Therapy in Treating Men With Stage IV Prostate Cancer

Prostate Cancer Clinical Trial

Official title:

Intermittent Androgen Deprivation in Patients With Stage D2 Prostate Cancer, Phase III

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00002651
• Other study ID #: CDR0000064184
• Secondary ID: SWOG-9346CAN-NCI
• Status: Recruiting
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: October 23, 2012
• Start date: May 1995

Study information

• Verified date: April 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1512
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• bicalutamide
Given orally
• 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.

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
Canada	Cross Cancer Institute at University of Alberta	Edmonton	Alberta
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	Hopital Notre-Dame du CHUM	Montreal	Quebec
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Ottawa Hospital Regional Cancer Centre - General Campus	Ottawa	Ontario
Canada	Centre Hospitalier Universitaire de Quebec	Quebec City	Quebec
Canada	Saskatoon Cancer Centre at the University of Saskatchewan	Saskatoon	Saskatchewan
Canada	CHUS-Hopital Fleurimont	Sherbrooke	Quebec
Canada	Odette Cancer Centre at Sunnybrook	Toronto	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia

Sponsors (6)

Lead Sponsor	Collaborator
Southwest Oncology Group	Canadian Cancer Trials Group, Cancer and Leukemia Group B, Eastern Cooperative Oncology Group, European Organisation for Research and Treatment of Cancer - EORTC, National Cancer Institute (NCI)

Country where clinical trial is conducted

Canada, 

References & Publications (9)

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 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. — View 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 — View 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.

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 C

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.

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, 201

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] Proc

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-specific symptoms as measured on the four-item Medical Outcomes Study Short Form-36 (SF-36) and Vitality scale			No
Primary	Physical functioning as measured by the SF-36			No
Primary	Emotional functioning as measured by the SF-36 Mental Health Inventory			No
Secondary	Symptoms as assessed by the Symptom Distress Scale			No
Secondary	Role functioning as assessed by the Role Functioning Scale SF-20			No
Secondary	Social functioning as assessed by the General Health Survey SF-20			No
Secondary	Global quality of life (QOL) and health-related QOL			No
Secondary	Comorbidity, social support, and demographic variables			No