Hormone Therapy in Treating Patients With Rising PSA Levels Following Radiation Therapy for Prostate Cancer
Study Details
Study Description
Brief Summary
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 or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
OBJECTIVES:
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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).
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Compare the time to the development of hormone resistance in patients treated with these regimens.
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Compare the quality of life of patients treated with these regimens.
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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.
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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.
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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.
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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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
Outcome Measures
Primary Outcome Measures
- Overall survival [2 years]
Secondary Outcome Measures
- Time to hormone resistance [2 years]
- Quality of life by European Organization for Research of the Treatment of Cancer Quality of Life Questionnaire-C30+ (EORTC QLQ-C30+) trial specific checklist [2 years]
- Serum cholesterol, high-density lipoprotein, and low-density lipoprotein levels [2 years]
- Duration of treatment and non-treatment interval during intermittent androgen suppression arm only [2 years]
- Time to testosterone recovery during intermittent androgen suppression arm only [2 years]
- Time to recovery of potency during intermittent androgen suppression arm only [2 years]
Eligibility Criteria
Criteria
DISEASE CHARACTERISTICS:
-
Histologically or cytologically proven adenocarcinoma of the prostate prior to the initiation of radiotherapy
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Prior pelvic radiotherapy for prostate cancer, either post-radical prostatectomy or as primary management
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More than 30 months since prior brachytherapy with curative intent
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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
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No definite evidence of metastatic disease
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Chest x-ray and bone scan negative for metastases
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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
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Fertile patients must use effective contraception
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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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
| 2 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 3 | BCCA - Cancer Centre for the Southern Interior | Kelowna | British Columbia | Canada | V1Y 5L3 |
| 4 | BCCA - Fraser Valley Cancer Centre | Surrey | British Columbia | Canada | V3V 1Z2 |
| 5 | Clinical Research Unit at Vancouver Coastal | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 6 | BCCA - Vancouver Cancer Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 7 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 8 | The Vitalite Health Network - Dr. Leon Richard | Moncton | New Brunswick | Canada | E1C 8X3 |
| 9 | Atlantic Health Sciences Corporation | Saint John | New Brunswick | Canada | E2L 4L2 |
| 10 | Dr. H. Bliss Murphy Cancer Centre | St. John's | Newfoundland and Labrador | Canada | AIB 3V6 |
| 11 | QEII Health Sciences Center | Halifax | Nova Scotia | Canada | B3H 1V7 |
| 12 | William Osler Health Centre, Brampton Memorial | Brampton | Ontario | Canada | L6R 3J7 |
| 13 | Juravinski Cancer Centre at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8V 5C2 |
| 14 | Cancer Centre of Southeastern Ontario at Kingston | Kingston | Ontario | Canada | K7L 5P9 |
| 15 | London Regional Cancer Program | London | Ontario | Canada | N6A 4L6 |
| 16 | Credit Valley Hospital | Mississauga | Ontario | Canada | L5M 2N1 |
| 17 | Ottawa Health Research Institute - General Division | Ottawa | Ontario | Canada | K1H 8L6 |
| 18 | Niagara Health System | St. Catharines | Ontario | Canada | L2R 7C6 |
| 19 | Northeast Cancer Center Health Sciences | Sudbury | Ontario | Canada | P3E 5J1 |
| 20 | Thunder Bay Regional Health Science Centre | Thunder Bay | Ontario | Canada | P7B 6V4 |
| 21 | Odette Cancer Centre | Toronto | Ontario | Canada | M4N 3M5 |
| 22 | Univ. Health Network-Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 23 | Windsor Regional Cancer Centre | Windsor | Ontario | Canada | N8W 2X3 |
| 24 | CHUM - Hopital Notre-Dame | Montreal | Quebec | Canada | H2L 4M1 |
| 25 | McGill University - Dept. Oncology | Montreal | Quebec | Canada | H2W 1S6 |
| 26 | CHUQ-Pavillon Hotel-Dieu de Quebec | Quebec City | Quebec | Canada | G1R 2J6 |
| 27 | Centre hospitalier universitaire de Sherbrooke | Sherbrooke | Quebec | Canada | J1H 5N4 |
| 28 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
| 29 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
Sponsors and Collaborators
- NCIC Clinical Trials Group
- National Cancer Institute (NCI)
- Southwest Oncology Group
Investigators
- Study Chair: Laurence H. Klotz, MD, Toronto Sunnybrook Regional Cancer Centre
- Study Chair: Celestia S. Higano, MD, University of Washington
Study Documents (Full-Text)
None provided.More Information
Publications
- PR7
- CAN-NCIC-PR7
- SWOG-JPR7
- ICR-CTSU-JPR7
- CDR0000066745