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Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00002633
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : April 3, 2020
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Southwest Oncology Group
Medical Research Council
Information provided by (Responsible Party):
Canadian Cancer Trials Group ( NCIC Clinical Trials Group )

Study Description
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Brief Summary:

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 or disease Intervention/treatment Phase
Prostate Cancer Drug: bicalutamide Drug: buserelin Drug: flutamide Drug: goserelin Drug: leuprolide acetate Drug: nilutamide Procedure: orchiectomy Radiation: radiation therapy Phase 3

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 361 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Actual Study Start Date : February 8, 1995
Actual Primary Completion Date : September 23, 2011
Actual Study Completion Date : January 6, 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
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Arm Intervention/treatment
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)


Outcome Measures
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Primary Outcome Measures :
  1. Overall survival [ Time Frame: 10 years ]

Secondary Outcome Measures :
  1. Disease specific survival [ Time Frame: 10 years ]
  2. Time to disease progression [ Time Frame: 10 years ]
  3. Symptomatic local control measured by surgical intervention rate [ Time Frame: 10 years ]
  4. Quality of life assessed by EORTC-QLQ-C30 + 3 and a trial-specific checklist (PR17) or the FACT-P questionnaire [ Time Frame: 10 years ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   up to 79 Years   (Child, Adult, Older Adult)
Sexes 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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00002633


Locations
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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
National Cancer Institute (NCI)
Eastern Cooperative Oncology Group
Southwest Oncology Group
Medical Research Council
Investigators
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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
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00002633    
Other Study ID Numbers: PR3
CAN-NCIC-PR3 ( Registry Identifier: NCI US PDQ )
ECOG-JPR03 ( Other Identifier: ECOG )
MRC-PR07 ( Other Identifier: MRC )
SWOG-JPR3 ( Other Identifier: SWOG )
EU-99013 ( Other Identifier: EU )
NCI-T94-0110O ( Other Grant/Funding Number: NCI )
ISRCTN24991896 ( Registry Identifier: ISRCTN )
CDR0000064065 ( Other Identifier: PDQ )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: April 3, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Canadian Cancer Trials Group ( NCIC Clinical Trials Group ):
adenocarcinoma of the prostate
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Leuprolide
Goserelin
Flutamide
Bicalutamide
 Nilutamide
Buserelin
Fertility Agents, Female
Fertility Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists