Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer

This study has been completed.
Sponsor:
Collaborators:
Southwest Oncology Group
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00003653
First received: November 1, 1999
Last updated: January 10, 2013
Last verified: August 2012
  Purpose

RATIONALE: Androgens can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. It is not yet known which androgen suppression regimen is more effective for prostate cancer.

PURPOSE: This randomized phase III trial is studying two hormone therapy regimens and comparing them to see how well they work in treating patients with rising PSA levels following radiation therapy for prostate cancer.


Condition Intervention Phase
Prostate Cancer
Drug: bicalutamide
Drug: buserelin
Drug: cyproterone acetate
Drug: flutamide
Drug: goserelin
Drug: leuprolide acetate
Drug: nilutamide
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Randomized Trial Comparing Intermittent Versus Continuous Androgen Suppression for Patients With Prostate-Specific-Antigen Progression in the Clinical Absence of Distant Metastases Following Radiotherapy for Prostate Cancer

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to hormone resistance [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Duration of treatment and non-treatment interval during intermittent androgen suppression arm only [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to testosterone recovery during intermittent androgen suppression arm only [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Time to recovery of potency during intermittent androgen suppression arm only [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 1386
Study Start Date: January 1999
Study Completion Date: January 2013
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Intermittent Androgen Suppression Drug: bicalutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: buserelin

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: cyproterone acetate

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: flutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: goserelin

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: leuprolide acetate

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: nilutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Active Comparator: Continuous Androgen Suppression Drug: bicalutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: buserelin

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: cyproterone acetate

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: flutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: goserelin

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: leuprolide acetate

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented

Drug: nilutamide

Patients on the IAS arm should receive a minimum of 4 weeks of antiandrogen and a total of 8 months of LHRH analog during each on-treatment interval. The dose and frequency of LHRH treatment will be determined by the drug being administered (Appendix IX). Patients on the IAS arm should not be given an LHRH analog injection at the end of month 8 unless the patient is transferred to continuous treatment as per protocol upon completion of the 8 month intermittent treatment.

Patients may be treated with any commercially available LHRH analog and antiandrogen during or after protocol treatment (Appendix IX). Patients may switch drugs at any time during or after protocol treatment. The dose and schedule of treatment will depend on the agent used. Patients should continue to receive hormone therapy without interruption until hormone resistance has been documented


Detailed Description:

OBJECTIVES:

  • Compare the survival of prostate cancer patients with prostate-specific antigen progression in the clinical absence of distant metastases after prior radical radiotherapy treated with intermittent androgen suppression (IAS) vs continuous androgen deprivation (CAD).
  • Compare the time to the development of hormone resistance in patients treated with these regimens.
  • Compare the quality of life of patients treated with these regimens.
  • Compare the serum cholesterol and HDL/LDL levels at 3 years with those at baseline and compare them annually in patients treated with these regimens.
  • Evaluate the duration of treatment and non-treatment intervals, time to testosterone recovery (return to pre-therapy levels), and time to recover potency in patients treated with IAS.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior radical prostatectomy (yes vs no), time since completion of prior radical radiotherapy (1 to 3 years vs 3 years or more), baseline prostate-specific antigen (PSA) value (3-15 ng/mL vs greater than 15 ng/mL), and prior hormonal therapy (neo-adjuvant, concurrent, or adjuvant cytoreduction in association with the radical radiotherapy treatment or prostatectomy for a maximum duration of 12 months and completed at least 12 months prior to randomization) (yes vs no). Patients are randomized to one of two treatment arms.

  • Arm I: Patients undergo intermittent androgen suppression (IAS). Patients receive luteinizing hormone-releasing hormone (LHRH) analog (buserelin [BSRL], goserelin [ZDX], or leuprolide [LEUP]) and an antiandrogen (nilutamide [ANAN], flutamide [FLUT], bicalutamide [CDX], or cyproterone acetate [CPTR]) for 8 months. Patients receive LHRH analog by subcutaneous (SC) or intramuscular (IM) implant every 1-4 months beginning within 5 days of randomization and oral antiandrogen 1-3 times daily, depending on the actual LHRH analog and antiandrogen. PSA levels are monitored every 2 months. If PSA falls to normal during the 8-month treatment period, therapy stops until levels rise to 10 ng/mL, at which time IAS resumes for another 8-month period. IAS continues as long as PSA levels are controlled. At the time of disease progression, patients begin continuous hormonal treatment similar to arm II.
  • Arm II: Patients undergo continuous androgen deprivation without scheduled interruptions. Patients receive LHRH analog (BSRL, ZDX, or LEUP) with an antiandrogen (ANAN, FLUT, CDX, or CPTR) OR undergo bilateral orchiectomy within 5 days of randomization and receive an antiandrogen. Patients receive LHRH analog by SC or IM implant every 1-4 months beginning within 5 days of randomization and oral antiandrogen 1-3 times daily, depending on the actual LHRH analog and antiandrogen. PSA levels are monitored every 2 months. Treatment continues until hormone resistance develops.

Patients receiving LHRH analog may begin antiandrogen therapy either prior to or simultaneously with LHRH analog and must continue antiandrogen therapy for at least 4 weeks to block tumor flare.

Quality of life is assessed at randomization, every 4 months for 2 years, every 8 months until development of hormone resistance, at the time of hormone resistance, and then annually thereafter.

Patients are followed annually for survival.

PROJECTED ACCRUAL: A total of 1,386 patients will be accrued for this study within 7 years.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically proven adenocarcinoma of the prostate prior to the initiation of radiotherapy
  • Prior pelvic radiotherapy for prostate cancer, either post-radical prostatectomy or as primary management

    • More than 30 months since prior brachytherapy with curative intent
  • Prostate-specific antigen must be rising and greater than 3 ng/mL and higher than the lowest level recorded previously since the end of radiotherapy (i.e., higher than the post-radiotherapy nadir)
  • Total testosterone greater than 5 nmol/L
  • No definite evidence of metastatic disease

    • Chest x-ray and bone scan negative for metastases
    • Radiological changes compatible with nonmalignant diseases allowed
  • Clinical evidence of local disease allowed

PATIENT CHARACTERISTICS:

Age:

  • 16 and over (18 and over for participating centers in the United Kingdom)

Performance status:

  • ECOG 0-1

Life expectancy:

  • More than 5 years

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST/ALT no greater than 1.5 times ULN
  • LDH no greater than 1.5 times ULN
  • No chronic liver disease

Renal:

  • Creatinine no greater than 1.5 times ULN

Other:

  • Sufficiently fluent and willing to complete the quality of life questionnaire in either English or French
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or superficial bladder cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior or concurrent biologic therapy

Chemotherapy:

  • No prior or concurrent chemotherapy

Endocrine therapy:

  • Prior hormonal therapy administered prior to, during, or immediately after radical radiotherapy or prostatectomy allowed provided duration was no longer than 12 months

    • At least 12 months since prior hormonal therapy

Radiotherapy:

  • See Disease Characteristics
  • At least 12 months since prior radiotherapy
  • No concurrent palliative radiotherapy

Surgery:

  • See Disease Characteristics
  • See Endocrine therapy

Other:

  • No concurrent bisphosphonates
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003653

Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, British Columbia
BCCA - Cancer Centre for the Southern Interior
Kelowna, British Columbia, Canada, V1Y 5L3
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada, V3V 1Z2
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Clinical Research Unit at Vancouver Coastal
Vancouver, British Columbia, Canada, V5Z 1M9
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
The Vitalite Health Network - Dr. Leon Richard
Moncton, New Brunswick, Canada, E1C 8X3
Atlantic Health Sciences Corporation
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Newfoundland and Labrador
Dr. H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, AIB 3V6
Canada, Nova Scotia
QEII Health Sciences Center
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
William Osler Health Centre, Brampton Memorial
Brampton, Ontario, Canada, L6R 3J7
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
Cancer Centre of Southeastern Ontario at Kingston
Kingston, Ontario, Canada, K7L 5P9
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Credit Valley Hospital
Mississauga, Ontario, Canada, L5M 2N1
Ottawa Health Research Institute - General Division
Ottawa, Ontario, Canada, K1H 8L6
Niagara Health System
St. Catharines, Ontario, Canada, L2R 7C6
Northeast Cancer Center Health Sciences
Sudbury, Ontario, Canada, P3E 5J1
Thunder Bay Regional Health Science Centre
Thunder Bay, Ontario, Canada, P7B 6V4
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Windsor Regional Cancer Centre
Windsor, Ontario, Canada, N8W 2X3
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
CHUQ-Pavillon Hotel-Dieu de Quebec
Quebec City, Quebec, Canada, G1R 2J6
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Canada, Saskatchewan
Allan Blair Cancer Centre
Regina, Saskatchewan, Canada, S4T 7T1
Saskatoon Cancer Centre
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
NCIC Clinical Trials Group
Southwest Oncology Group
Investigators
Study Chair: Laurence H. Klotz, MD Edmond Odette Cancer Centre at Sunnybrook
Study Chair: Celestia S. Higano, MD University of Washington
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00003653     History of Changes
Other Study ID Numbers: PR7, CAN-NCIC-PR7, SWOG-JPR7, ICR-CTSU-JPR7, CDR0000066745
Study First Received: November 1, 1999
Last Updated: January 10, 2013
Health Authority: Canada: Health Canada
United States: Federal Government

Keywords provided by NCIC Clinical Trials Group:
adenocarcinoma of the prostate
recurrent prostate cancer

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Androgens
Buserelin
Leuprolide
Cyproterone Acetate
Cyproterone
Diane
Flutamide
Nilutamide
Bicalutamide
Goserelin
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Therapeutic Uses
Androgen Antagonists
Hormone Antagonists
Antineoplastic Agents
Contraceptive Agents, Male
Contraceptive Agents

ClinicalTrials.gov processed this record on April 15, 2014