Hormone Therapy With or Without Surgery or Radiation Therapy in Treating Patients With Prostate Cancer - Full Text View

Sponsor:	NCIC Clinical Trials Group
Collaborators:	National Cancer Institute (NCI) Eastern Cooperative Oncology Group Cancer and Leukemia Group B Southwest Oncology Group Medical Research Council
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00002633

Purpose

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	Intervention	Phase
Prostate Cancer	Drug: bicalutamide Drug: buserelin Drug: flutamide Drug: goserelin Drug: leuprolide acetate Drug: nilutamide Procedure: orchiectomy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer Surgery

Drug Information available for: Flutamide Leuprolide Buserelin Nilutamide Goserelin Buserelin acetate Leuprolide acetate Bicalutamide

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease specific survival [ Designated as safety issue: No ]
Time to disease progression [ Designated as safety issue: No ]
Symptomatic local control measured by surgical intervention rate [ 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 [ Designated as safety issue: No ]

Estimated Enrollment:	1200
Study Start Date:	March 1995
Estimated Primary Completion Date:	August 2011 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	up to 79 Years
Genders 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002633

Locations

United States, Alabama
East Alabama Medical Center
Opelika, Alabama, United States, 36801-5452
United States, Hawaii
Tripler Army Medical Center
Honolulu, Hawaii, United States, 96859
United States, Illinois
Good Samaritan Regional Health Center
Mt. Vernon, Illinois, United States, 62864
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
United States, Louisiana
Feist-Weiller Cancer Center at Louisiana State University Health Sciences
Shreveport, Louisiana, United States, 71130-3932
Veterans Affairs Medical Center - Shreveport
Shreveport, Louisiana, United States, 71101
United States, Missouri
CCOP - St. Louis-Cape Girardeau
St. Louis, Missouri, United States, 63141
David C. Pratt Cancer Center at St. John's Mercy
Saint Louis, Missouri, United States, 63141
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
Gape Girardeau, Missouri, United States, 63701
St. Francis Medical Center
Cape Girardeau, Missouri, United States, 63701
United States, Texas
Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229
University Hospital - San Antonio
San Antonio, Texas, United States, 78229
University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78284-7811
Veterans Affairs Medical Center - San Antonio (Murphy)
San Antonio, Texas, United States, 78209
United States, Virginia
Sentara Cancer Institute at Sentara Norfolk General Hospital
Norfolk, Virginia, United States, 23507
United Kingdom, Wales
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL

Sponsors and Collaborators

NCIC Clinical Trials Group

National Cancer Institute (NCI)

Eastern Cooperative Oncology Group

Cancer and Leukemia Group B

Southwest Oncology Group

Medical Research Council

Investigators

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

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000064065, CAN-NCIC-PR3, CALGB-9593, ECOG-JPR03, MRC-PR07, SWOG-JPR3, EU-99013, NCI-T94-0110O, ISRCTN24991896
Study First Received:	November 1, 1999
Last Updated:	April 3, 2009
ClinicalTrials.gov Identifier:	NCT00002633 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the prostate
stage II prostate cancer
stage III prostate cancer
stage IV prostate cancer

Additional relevant MeSH terms:

Buserelin
Antineoplastic Agents, Hormonal
Genital Neoplasms, Male
Prostatic Diseases
Antineoplastic Agents
Nilutamide
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Goserelin
Urogenital Neoplasms
Reproductive Control Agents

Genital Diseases, Male
Flutamide
Pharmacologic Actions
Androgen Antagonists
Neoplasms
Neoplasms by Site
Leuprolide
Therapeutic Uses
Fertility Agents, Female
Fertility Agents
Bicalutamide
Prostatic Neoplasms

ClinicalTrials.gov processed this record on November 27, 2009