Clinical trial NCT00002633: Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Eastern Cooperative Oncology Group
name: SWOG Cancer Research Network
name: Medical Research Council
First posted: 2003-01-27
Enrollment: 361
Sex: MALE
Maximum age (years): 79
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Overall survival
timeFrame: 10 years
Secondary outcomes:
measure: Disease specific survival
timeFrame: 10 years
measure: Time to disease progression
timeFrame: 10 years
measure: Symptomatic local control measured by surgical intervention rate
timeFrame: 10 years
measure: Quality of life assessed by EORTC-QLQ-C30 + 3 and a trial-specific checklist (PR17) or the FACT-P questionnaire
timeFrame: 10 years
Other outcomes:
Locations:
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences Center
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: Kingston
country: Canada
facility: Cancer Centre of Southeastern Ontario at Kingston
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Health Research Institute - General Division
state: Ontario
city: Sudbury
country: Canada
facility: Regional Cancer Program of the Hopital Regional
state: Ontario
city: Thunder Bay
country: Canada
facility: Thunder Bay Regional Health Science Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Saskatoon
country: Canada
facility: Saskatoon Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Padraig R. Warde, MB, MRCPI, FRCPC
role: STUDY_CHAIR
affiliation: Abramson Cancer Center at Penn Medicine
name: Richard R. Whittington, MD
role: STUDY_CHAIR
affiliation: Michael Reese Hospital and Medical Center
name: Srinivasan Vijayakumar, MD
role: STUDY_CHAIR
affiliation: Brooke Army Medical Center
name: Patricia Lillis-Hearne, MD
role: STUDY_CHAIR
affiliation: Velindre NHS Trust
name: Malcolm D. Mason, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: Brundage M, Sydes MR, Parulekar WR, Warde P, Cowan R, Bezjak A, Kirkbride P, Parliament M, Moynihan C, Bahary JP, Parmar MK, Sanders K, Chen BE, Mason MD. Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial. J Clin Oncol. 2015 Jul 1;33(19):2151-7. doi: 10.1200/JCO.2014.57.8724. Epub 2015 May 26.
citation: Mason MD, Parulekar WR, Sydes MR, Brundage M, Kirkbride P, Gospodarowicz M, Cowan R, Kostashuk EC, Anderson J, Swanson G, Parmar MK, Hayter C, Jovic G, Hiltz A, Hetherington J, Sathya J, Barber JB, McKenzie M, El-Sharkawi S, Souhami L, Hardman PD, Chen BE, Warde P. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer. J Clin Oncol. 2015 Jul 1;33(19):2143-50. doi: 10.1200/JCO.2014.57.7510. Epub 2015 Feb 17.