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Radiation Therapy With or Without Antiandrogen Therapy in Treating Patients With Stage I or Stage II Prostate Cancer

Phase 3
Completed
Conditions
Prostate Cancer
Interventions
Radiation: radiation therapy
Registration Number
NCT00002597
Lead Sponsor
Radiation Therapy Oncology Group
Brief Summary

RATIONALE: Radiation therapy (RT) uses high-energy x-rays to damage tumor cells. Androgens can stimulate the growth of prostate cancer cells. Hormone therapy using flutamide, goserelin, and leuprolide may fight prostate cancer by reducing the production of androgens. It is not yet known which regimen of antiandrogen therapy is most effective for prostate cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of radiation therapy with or without antiandrogen therapy in treating patients who have stage I or stage II prostate cancer.

Detailed Description

OBJECTIVES: Primary: To evaluate whether a combination of Zoladex and flutamide used as cytoreductive agents prior to and during definitive radiation therapy improves overall survival over radiation therapy alone in locally confined carcinomas of the prostate; Secondary: To compare the rates of disease-specific survival, clinical relapse (local progression and/or distant failure), freedom from prostate-specific antigen (PSA) failure, freedom from second clinical relapse, freedom from second PSA relapse, and disease-free survival; To compare the prostate re-biopsy at two years; To measure the effect on sexual function.

OUTLINE: This is a randomized, multicenter study. Patients were stratified by PSA level (less than 4 vs 4-20), tumor differentiation (well vs moderate vs poor), nodal status (N0 \[nodes evaluated by surgical sampling\] vs NX \[nodes evaluated negative by imaging methods only\]), and participating center. Patients are randomized to one of two treatment arms. Arm I: Patients receive oral flutamide 3 times a day and goserelin subcutaneously once every 4 weeks, or once as a time release injection (intramuscular leuprolide may be substituted for goserelin), beginning 2 months prior to radiotherapy and continuing until completion of radiotherapy. Patients undergo radiotherapy daily 4-5 days per week for almost 8 weeks. Arm II: Patients undergo radiotherapy only, as in arm I. Patients are followed every 3 months for the remainder of the first year, every 4 months for the second year, every 6 months for the third through fifth years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1980 patients within 5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
2028
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Radiation therapy aloneradiation therapyRadiation therapy alone
Neoadjuvant TAS + RTZoladexNeoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Neoadjuvant TAS + RTradiation therapyNeoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Neoadjuvant TAS + RTflutamideNeoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Neoadjuvant TAS + RTLupronNeoadjuvant total androgen suppression (TAS) - Flutamide and Zoladex or Lupron - two months before and during radiation therapy.
Primary Outcome Measures
NameTimeMethod
Overall Survival Rate (10-year)From date of randomization to 10 years

Overall survival (OS) was calculated from randomization to the date of death from any cause and overall survival rates were estimated by the Kaplan-Meier method.

Secondary Outcome Measures
NameTimeMethod
Disease-specific Survival Rate (10 Years)From registration to 10 years

Disease-specific failure is defined as death certified as due to prostate cancer (by central review), death due to complications of treatment (irrespective of malignancy status), death from unknown causes with active malignancy, or death from unknown causes with previously documented relapse (either clinical or biochemical). Survival rates were estimated by means of cumulative incidence functions.

Local Progression Rate (10 Years)From registration to 10 years

Local progression defined as documented local progression as determined by clinical exam . Failure rates were estimated by means of cumulative incidence functions.

Distant Failure Rate (10 Years)From registration to 10 years

Failure is defined as documented metastatic disease. Failure rates were estimated by means of cumulative incidence functions.

Disease-free Survival Rate (10 Years)From registration to 10 years

Disease-free failure is defined as documentation of progression (local progression, distant failure, and biochemical failure) or death from any cause. Disease-free survival rates were estimated by the Kaplan-Meier method.

Second Biochemical Relapse Rate (10 Years)From registration to 10 years

Second biochemical relapse is as defined as follows (after initiation of salvage hormone therapy): A rise in PSA on at least two consecutive cases above the nadir (after initiation of salvage hormone therapy), with the rises in PSA exceeding 1 ng/ml above the nadir; or failure to reach 4 ng/L or less at 18 months. The rates of second biochemical relapse were estimated by means of cumulative incidence functions.

Biochemical Failure Rate (10 Years)From registration to 10 years

The Phoenix definition of biochemical failure was used - an increase in the prostate-specific antigen (PSA) level of \>2 ng per milliliter above the nadir. Failure rates were estimated by means of cumulative incidence functions.

Clinical Relapse Rate (10 Years)From registration to 10 years

Clinical relapse is defined as local progression or distant metastases. Failure rates were estimated by means of cumulative incidence functions.

Positive Re-biopsy Rate at Two YearsFrom registration to two years

The rate of prostate rebiopsy at two years is defined as the proportion of patients whose results are positive among all eligible patients who had a repeat biopsy at two years. The rate was estimated separately in each arm.

Trial Locations

Locations (239)

University of Alabama at Birmingham Comprehensive Cancer Center

🇺🇸

Birmingham, Alabama, United States

Huntsville Hospital System

🇺🇸

Huntsville, Alabama, United States

Comprehensive Cancer Institute of Huntsville

🇺🇸

Huntsville, Alabama, United States

MBCCOP - Gulf Coast

🇺🇸

Mobile, Alabama, United States

Alabama Oncology, LLC

🇺🇸

Montgomery, Alabama, United States

Radiation Oncology Associates of West Alabama

🇺🇸

Tuscaloosa, Alabama, United States

Providence Alaska Medical Center

🇺🇸

Anchorage, Alaska, United States

Arizona Cancer Center

🇺🇸

Tucson, Arizona, United States

Mount Diablo Medical Center

🇺🇸

Concord, California, United States

Cancer Center and Beckman Research Institute, City of Hope

🇺🇸

Duarte, California, United States

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University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States

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