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

Prostate Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002633
• Other study ID #: PR3
• Secondary ID: CAN-NCIC-PR3ECOG
• Status: Completed
• Phase: Phase 3
• Start date: February 8, 1995
• Est. completion date: January 6, 2012

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 361
• Est. completion date: January 6, 2012
• Est. primary completion date: September 23, 2011
• Accepts healthy volunteers: No
• Gender: Male
• Age group: N/A to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

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
• 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
• 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
• 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
• 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
• 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)

Locations

Country	Name	City	State
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	QEII Health Sciences Center	Halifax	Nova Scotia
Canada	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario
Canada	Cancer Centre of Southeastern Ontario at Kingston	Kingston	Ontario
Canada	London Regional Cancer Program	London	Ontario
Canada	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Ottawa Health Research Institute - General Division	Ottawa	Ontario
Canada	Saskatoon Cancer Centre	Saskatoon	Saskatchewan
Canada	Regional Cancer Program of the Hopital Regional	Sudbury	Ontario
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	Windsor Regional Cancer Centre	Windsor	Ontario

Sponsors (5)

Lead Sponsor	Collaborator
NCIC Clinical Trials Group	Eastern Cooperative Oncology Group, Medical Research Council, National Cancer Institute (NCI), Southwest Oncology Group

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. C — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		10 years
Secondary	Disease specific survival		10 years
Secondary	Time to disease progression		10 years
Secondary	Symptomatic local control measured by surgical intervention rate		10 years
Secondary	Quality of life assessed by EORTC-QLQ-C30 + 3 and a trial-specific checklist (PR17) or the FACT-P questionnaire		10 years