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

This study has been completed.
Sponsor:
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: January 31, 2014
Last verified: January 2012

November 1, 1999
January 31, 2014
March 1995
December 2010   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
Not Provided
Complete list of historical versions of study NCT00002633 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Prostate Cancer
  • 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)
  • Active Comparator: Total Androgen Blockade
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: flutamide
    • Drug: goserelin
    • Drug: leuprolide acetate
    • Drug: nilutamide
    • Procedure: orchiectomy
  • Active Comparator: Total Androgen Blockade Vs TA Blockade Plus Pelvic Irradiation
    Interventions:
    • Drug: bicalutamide
    • Drug: buserelin
    • Drug: flutamide
    • Drug: goserelin
    • Drug: leuprolide acetate
    • Drug: nilutamide
    • Procedure: orchiectomy
    • Radiation: radiation therapy
Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC CTG PR.3/MRC UK PR07 investigators. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. doi: 10.1016/S0140-6736(11)61095-7. Epub 2011 Nov 2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
361
January 2012
December 2010   (final data collection date for primary outcome measure)

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
Male
up to 79 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00002633
PR3, CAN-NCIC-PR3, ECOG-JPR03, MRC-PR07, SWOG-JPR3, EU-99013, NCI-T94-0110O, ISRCTN24991896, CDR0000064065
Yes
NCIC Clinical Trials Group
NCIC Clinical Trials Group
  • National Cancer Institute (NCI)
  • Eastern Cooperative Oncology Group
  • Southwest Oncology Group
  • Medical Research Council
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
NCIC Clinical Trials Group
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP