Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer
This study has been completed.
Sponsor:
NCIC Clinical Trials Group
Collaborators:
Eastern Cooperative Oncology Group
Southwest Oncology Group
Medical Research Council
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00002633
First received: November 1, 1999
Last updated: May 30, 2013
Last verified: January 2012
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Purpose
RATIONALE: Hormones can stimulate the growth of prostate cancer cells. Hormone therapy may fight prostate cancer by reducing the production of androgens. Radiation therapy uses high-energy x-rays to damage tumor cells. It is not yet known whether hormone therapy plus surgery is more effective than hormone therapy plus radiation therapy for prostate cancer.
PURPOSE: This randomized phase III trial is studying giving hormone therapy alone to see how well it works compared to giving hormone therapy together with bilateral orchiectomy or radiation therapy in treating patients with stage III or stage IV prostate cancer.
| Condition | Intervention | Phase |
|---|---|---|
|
Prostate Cancer |
Drug: bicalutamide Drug: buserelin Drug: flutamide Drug: goserelin Drug: leuprolide acetate Drug: nilutamide Procedure: orchiectomy Radiation: radiation therapy |
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: | Phase III Randomized Trial Comparing Total Androgen Blockade Versus Total Androgen Blockade Plus Pelvic Irradiation in Clinical Stage T3-4, N0, M0 Adenocarcinoma of the Prostate |
Resource links provided by NLM:
Drug Information available for:
Flutamide
Nilutamide
Goserelin
Leuprolide acetate
Bicalutamide
Goserelin acetate
U.S. FDA Resources
Further study details as provided by NCIC Clinical Trials Group:
Primary Outcome Measures:
- Overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Disease specific survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Time to disease progression [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Symptomatic local control measured by surgical intervention rate [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Quality of life assessed by EORTC-QLQ-C30 + 3 and a trial-specific checklist (PR17) or the FACT-P questionnaire [ Time Frame: 10 years ] [ Designated as safety issue: No ]
| Enrollment: | 361 |
| Study Start Date: | March 1995 |
| Study Completion Date: | January 2012 |
| Primary Completion Date: | December 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Active Comparator: Total Androgen Blockade |
Drug: bicalutamide
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: buserelin
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: flutamide
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: goserelin
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: leuprolide acetate
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: nilutamide
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Procedure: orchiectomy
Optional orchiectomy
|
| Active Comparator: Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation |
Drug: bicalutamide
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: buserelin
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: flutamide
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: goserelin
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: leuprolide acetate
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Drug: nilutamide
Antiandrogen (optional with orchiectomy) Flutamide 250 mg po TID or Nilutamide 100 mg po TID x 1 mo; then 150 mg po QD or Bicalutamide 50 mg po QD PLUS (patient's choice) Bilateral orchiectomy or LHRH agonist Goserelin 3.6 mg SC (abd) q28d or 10.8 mg SC (abd) Q3mos or Leuprolide 7.5 mg IM q28d (Leuprorelin 3.75 mg) or 22.5 mg IM Q3mos (Leuprorelin 11.25 mg) or 30 mg IM Q4mos or Buserelin 6.3mg SC (abd) Q8wk or 9.45mg SC (abd) Q12wk
Procedure: orchiectomy
Optional orchiectomy
Radiation: radiation therapy
Radical Radiation Therapy - (65-69 Gy; 35-37 treatments)
|
Detailed Description:
OBJECTIVES:
- Compare the overall survival, disease specific survival, and time to progression in patients with locally advanced adenocarcinoma of the prostate treated with total androgen suppression with or without pelvic irradiation.
- Compare the symptomatic control as measured by the rates of surgical interventions needed for control of local disease (e.g., transurethral resections, stent insertions, nephrostomies, and colostomies) in patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
- Compare the sensitivity of the EORTC-QLQ-C30+3 and a trial-specific checklist (PR17) with the FACT-P questionnaire in measuring changes in quality of life of patients treated with these regimens.
OUTLINE: This a randomized, multicenter study. Patients are stratified according to center, initial PSA level (less than 20 vs 20-50 vs greater than 50 ng/mL), method of node staging (clinical [no CT scan] vs radiological [CT scan negative] vs surgical), Gleason score (less than 8 vs 8-10), prior hormonal therapy (excluding orchiectomy) (yes vs no), and choice of hormonal therapy (bilateral orchiectomy with or without antiandrogen vs luteinizing hormone-releasing hormone [LHRH] with antiandrogen). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive antiandrogen therapy comprising oral flutamide every 8 hours, oral nilutamide every 8 hours for 1 month and then once daily, or oral bicalutamide once daily. Patients also choose to undergo bilateral orchiectomy or LHRH agonist therapy comprising goserelin subcutaneously (SC) every 4 weeks (short-acting formulation) or every 3 months (long-acting formulation), leuprolide intramuscularly every 4 weeks (short-acting formulation) or every 3 months (long-acting formulation), or buserelin SC every 8 weeks or every 12 weeks. Patients choosing orchiectomy may receive an antiandrogen for at least 6 weeks before surgery to counter any flare phenomenon and may continue the antiandrogen after surgery (at the physician's discretion).
- Arm II: Patients undergo total androgen ablation as in arm I. Patients with node-negative dissection undergo radiotherapy 5 days a week for 6.5-7 weeks. All other patients undergo radiotherapy 5 days a week for 5 weeks, followed by boost radiotherapy 5 days a week for 2-2.4 weeks.
Hormonal therapy on both arms continues in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, on the last day of radiotherapy, at 6 months, and then every 6 months thereafter.
Patients are followed at 1, 2, and 6 months and then every 6 months thereafter.
PROJECTED ACCRUAL: A total of 1,200 patients will be accrued for this study within 7.5 years.
Eligibility| Ages Eligible for Study: | up to 79 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Criteria
DISEASE CHARACTERISTICS:
Histologically proven locally advanced adenocarcinoma of the prostate, defined as 1 of the following:
- T3-4, N0 or NX, M0
- T2, PSA greater than 40 µg/L
- T2, PSA greater than 20 µg/L AND Gleason score at least 8
- Diagnosis made within the past 6 months
- Gleason score and PSA known
Pelvic lymph nodes must be clinically negative
- Lymph nodes no more than 1.5 cm in greatest diameter by CT scan or MRI of the pelvis
- Negative needle aspirate required for any lymph node more than 1.5 cm
- If a lymph node dissection was performed, it must be histologically negative
- No small cell or transitional cell carcinoma by biopsy
- No bony metastases by bone scan
PATIENT CHARACTERISTICS:
Age:
- Under 80
Performance status:
- ECOG 0-2
Life expectancy:
- At least 5 years excluding malignancy
Hematopoietic:
- Hemoglobin at least 10.0 g/dL
- WBC at least 2,000/mm^3
- Platelet count at least 100,000/mm^3
Hepatic:
- Bilirubin less than 2 times upper limit of normal (ULN)
- SGOT and SGPT less than 2 times ULN
- Alkaline phosphatase less than 2 times ULN
- No history of chronic liver disease
Renal:
- Creatinine less than 2 times ULN
Other:
- No contraindication to wide-field pelvic irradiation (e.g., inflammatory bowel disease or severe bladder irritability)
- No other malignancy within the past 5 years except nonmelanoma skin cancer
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Not specified
Endocrine therapy:
Prior hormonal therapy within the past 12 weeks allowed provided the following conditions are met:
- Negative bone scan before beginning any hormonal therapy
- Extracapsular extension remains palpable on rectal re-exam
- Baseline PSA known before beginning any hormonal therapy
- At least 4-6 weeks since prior 5-alpha-reductase inhibitor (e.g., finasteride) for benign prostatic hypertrophy
Radiotherapy:
- No prior pelvic irradiation
Surgery:
- No prior radical prostatectomy
- Prior transurethral resection of the prostate allowed
Other:
- No prior cytotoxic anticancer therapy
- No other prior treatment for prostate cancer
- No other concurrent anticancer therapy unless documented disease progression
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002633
Locations
| Canada, Alberta | |
| Cross Cancer Institute | |
| Edmonton, Alberta, Canada, T6G 1Z2 | |
| Canada, British Columbia | |
| BCCA - Fraser Valley Cancer Centre | |
| Surrey, British Columbia, Canada, V3V 1Z2 | |
| BCCA - Vancouver Cancer Centre | |
| Vancouver, British Columbia, Canada, V5Z 4E6 | |
| Canada, Nova Scotia | |
| QEII Health Sciences Center | |
| Halifax, Nova Scotia, Canada, B3H 1V7 | |
| Canada, Ontario | |
| 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 | |
| Ottawa Health Research Institute - General Division | |
| Ottawa, Ontario, Canada, K1H 8L6 | |
| Regional Cancer Program of the Hopital Regional | |
| Sudbury, Ontario, Canada, P3E 5J1 | |
| Thunder Bay Regional Health Science Centre | |
| Thunder Bay, Ontario, Canada, P7B 6V4 | |
| 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 | |
| Canada, Saskatchewan | |
| Saskatoon Cancer Centre | |
| Saskatoon, Saskatchewan, Canada, S7N 4H4 | |
Sponsors and Collaborators
NCIC Clinical Trials Group
Eastern Cooperative Oncology Group
Southwest Oncology Group
Medical Research Council
Investigators
| Study Chair: | Padraig R. Warde, MB, MRCPI, FRCPC | Princess Margaret Hospital, Canada |
| Study Chair: | Richard R. Whittington, MD | Abramson Cancer Center of the University of Pennsylvania |
| Study Chair: | Srinivasan Vijayakumar, MD | Michael Reese Hospital and Medical Center |
| Study Chair: | Patricia Lillis-Hearne, MD | Brooke Army Medical Center |
| Study Chair: | Malcolm D. Mason, MD | Velindre NHS Trust |
More Information
Additional Information:
No publications provided by NCIC Clinical Trials Group
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | NCIC Clinical Trials Group |
| ClinicalTrials.gov Identifier: | NCT00002633 History of Changes |
| Other Study ID Numbers: | PR3, CAN-NCIC-PR3, ECOG-JPR03, MRC-PR07, SWOG-JPR3, EU-99013, NCI-T94-0110O, ISRCTN24991896, CDR0000064065 |
| Study First Received: | November 1, 1999 |
| Last Updated: | May 30, 2013 |
| Health Authority: | Canada: Health Canada United States: Federal Government |
Keywords provided by NCIC Clinical Trials Group:
|
adenocarcinoma of the prostate stage II prostate cancer stage III prostate cancer stage IV prostate cancer |
Additional relevant MeSH terms:
|
Adenocarcinoma Prostatic Neoplasms Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Genital Neoplasms, Male Urogenital Neoplasms Neoplasms by Site Genital Diseases, Male Prostatic Diseases Androgens Buserelin Leuprolide Flutamide |
Goserelin Nilutamide Bicalutamide Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Pharmacologic Actions Fertility Agents, Female Fertility Agents Reproductive Control Agents Therapeutic Uses Antineoplastic Agents, Hormonal Antineoplastic Agents Androgen Antagonists Hormone Antagonists |
ClinicalTrials.gov processed this record on June 18, 2013