Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Treatment Closed Under 80 NCI CAN-NCIC-PR3 CALGB-9593, ECOG-JPR03, MRC-PR07, SWOG-JPR3, EU-99013, NCI-T94-0110O, ISRCTN24991896, T94-0110, NCT00002633, PR3

Objectives

1. Compare the overall survival and time to progression in patients with locally advanced adenocarcinoma of the prostate treated with total androgen suppression with or without pelvic irradiation.
2. 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.
3. Compare the quality of life of patients treated with these regimens.
4. 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.

Entry 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

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

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/mm³
• Platelet count at least 100,000/mm³

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

Expected Enrollment

A total of 1,200 patients will be accrued for this study within 7.5 years.

Outcomes

Overall survival

Time to disease progression
Symptomatic local control measured by surgical intervention rate
Quality of life assessed by EORTC-QLQ-C30 + 3 and a trial-specific checklist (PR17) or the FACT-P questionnaire

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.

Trial Contact Information

Trial Lead Organizations

NCIC-Clinical Trials Group

Padraig Warde, MB, MRCPI, FRCPC, Protocol chair		Ph: 416-946-2122 Email: padraig.warde@rmp.uhn.on.ca

Eastern Cooperative Oncology Group

Richard Whittington, MD, Protocol chair		Ph: 215-823-5855 Email: whittington@xrt.upenn.edu

Cancer and Leukemia Group B

Srinivasan Vijayakumar, MD, Protocol chair		Ph: 312-791-2514 Email: vijay@rover.uchicago.edu

Southwest Oncology Group

Patricia Lillis-Hearne, MD, Protocol chair(Contact information may not be current)		Ph: 210-916-0504

Medical Research Council Clinical Trials Unit

Malcolm Mason, MD, Protocol chair		Ph: 44-29-2031-6964 Email: masonmd@cardiff.ac.uk

Registry Information
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
Trial Start Date		1995-03-08
Trial Completion Date		2011-08-01 (estimated)
Registered in ClinicalTrials.gov		NCT00002633
Date Submitted to PDQ		1995-02-15
Information Last Verified		2007-06-02
NCI Grant/Contract Number		CM17107