Hormone Therapy and Radiation Therapy in Treating Patients With Prostate Cancer

Phase 3

Completed

Conditions: Prostate Cancer

Interventions: Drug: Casodex
Drug: Eulexin
Drug: LHRH agonist
Radiation: radiation therapy

Registration Number: NCT00005044

Lead Sponsor: Radiation Therapy Oncology Group

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 which regimen of hormone therapy and radiation therapy is more effective for prostate cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of two different regimens of hormone therapy and radiation therapy in treating patients who have prostate cancer.

Detailed Description: OBJECTIVES:

* Compare the efficacy of moderate-duration (28 weeks) neoadjuvant total androgen suppression (TAS) and radiotherapy (RT) with short-duration (8 weeks) neoadjuvant TAS and RT, as related to disease-specific survival, in patients with intermediate-risk adenocarcinoma of the prostate.

* Compare these regimens, in terms of overall survival, disease-free survival, time to local tumor progression or distant failure, time to first biochemical failure, hormone-refractory state, and treatment-induced morbidity, in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prostate-specific antigen level (no greater than 10 ng/mL vs greater than 10 but no greater than 20 ng/mL vs greater than 20 ng/mL), tumor stage (T1b-2 vs T3-4), Gleason score (2-4 vs 5-6 vs 7-10), and prior hormonal therapy (yes vs no). Patients are randomized to one of two treatment arms.

* Arm I: Patients receive total androgen suppression for 8 weeks prior to the initiation of radiotherapy and throughout radiotherapy. A luteinizing hormone-releasing hormone (LHRH) agonist is administered every 1-3 months AND bicalutamide OR flutamide is given orally daily for a total duration of 16 weeks. Beginning with week 9, patients undergo radiotherapy 5 days a week for 8 weeks.

* Arm II: Patients receive total androgen suppression for 28 weeks prior to the initiation of radiotherapy and throughout radiotherapy. An LHRH agonist AND bicalutamide OR flutamide are administered as in arm I for a total duration of 36 weeks. Beginning with week 29, patients undergo radiotherapy as in arm I.

Patients are followed every 3 months for 1 year, every 6 months for 4 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 1,540 patients (770 per treatment arm) will be accrued for this study within 4 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 1579

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAS x 8 weeks	Casodex	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 28 weeks	LHRH agonist	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 8 weeks	LHRH agonist	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 8 weeks	radiation therapy	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 28 weeks	Casodex	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 28 weeks	radiation therapy	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 8 weeks	Eulexin	Total Androgen Suppression (TAS) (LHRH agonist and Casodex or Eulexin) x 8 weeks followed by radiation therapy (RT) with concurrent TAS (LHRH agonist and Casodex or Eulexin).
TAS x 28 weeks	Eulexin	TAS (LHRH agonist and Casodex or Eulexin) x 28 weeks followed by RT with concurrent TAS (LHRH agonist and Casodex or Eulexin).

Primary Outcome Measures

Name	Time	Method
Disease-specific Survival (DSS) (10-year Rates Reported)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Disease-specific survival time is measured from date of randomization to death due to prostate cancer based on study chair review, with prostate-cancer death defined as (1) primary cause of death certified as due to prostate cancer, (2) complication of therapy, irrespective of disease status, (3) disease progression in the absence of any anti-tumor therapy, or (4) a 1.0 ng/ml-exceeding-rise in serum prostate-specific antigen (PSA) level on at least two consecutive occasions that occurs during or after salvage androgen suppression therapy. Death due to other causes is considered a competing risk. All others are censored. DSS is estimated using the cumulative incidence method. Ten-year rate is reported.

Secondary Outcome Measures

Name	Time	Method
Disease-free Survival (DFS) (10-year Rates Reported)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Disease-free survival time is defined as time from randomization to the date of disease progression or death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Ten-year rate is reported.
Overall Survival (OS) (10-year Rates Reported)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Survival time is defined as time from randomization to the date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Ten-year rate is reported.
Time to First Biochemical Failure (BF) (10-year Rates Reported)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Protocol definition: Time to BF measured from date of randomization to first of (1) the midway date between the last non-rising PSA and the first rising PSA of three consecutive rises or (2) the date of the initiation of salvage hormone therapy; competing risks are LRP, DM, and death without BF; all others are censored. Phoenix definition: Time to BF measured from date of randomization to first of (1) the date of documented rise of 2 ng/ml above the post-treatment(RT end date) nadir or (2) the date of the initiation of salvage hormone therapy; competing risks are LRP, DM, and death without BF; all others are censored. For both definitions BF is estimated using the cumulative incidence method. Ten year rates reported.
Time to Second Biochemical Failure (SBF) (10-year Rates Reported)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Time to SBF measured from date of randomization to the date of PSA increase of ≥1.0 ng/mL (from the nadir PSA after completion of protocol-specified therapy) after salvage androgen suppression was started; competing risks LRP, DM, and death without SBF; all others are censored. SBF is estimated using the cumulative incidence method. Ten-year rates are reported.
Clinical Patterns of Tumor Recurrence: Time to Locoregional Progression (LRP) and Time to Distant Metastasis (DM) (10 Year Rates Reported)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Time to distant metastasis measured from date of randomization to date of documented distant metastasis; competing risks are BF, LRP, and death without DM; all others are censored. Time to locoregional progression measured from date of randomization to date of documented local or regional progression; competing risks are BF \[protocol definition- first of (1) the midway date between the last non-rising PSA and the first rising PSA of three consecutive rises or (2) the date of the initiation of salvage hormone therapy\], DM, and death without LRP; all others are censored. LRP and DM are estimated using the cumulative incidence method. Ten -year rates are reported.
Treatment-induced Morbidity (Highest Grade Toxicity Reported Per Patient)	From randomization to 10 years. (Patients are followed until death or study termination, whichever occurs first.)	Acute drug therapy and radiation (\<= 90 days from start of RT) toxicity was graded using the Common Toxicity Criteria (CTC) v.2.0 criteria; late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for Research and Treatment of Cancer (EORTC) Late Radiation Morbidity Scoring schema. Grade refers to the severity of the toxicity. The CTC v2.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each toxicity based on this general guideline: Grade 1 Mild toxicity, Grade 2 Moderate toxicity, Grade 3 Severe toxicity, Grade 4 Life-threatening or disabling toxicity, Grade 5 Death related to toxicity. The highest grade acute and late toxicity was determined for each patient.

Trial Locations

Locations (261): University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
Comprehensive Cancer Institute
🇺🇸
Huntsville, Alabama, United States
Huntsville Hospital
🇺🇸
Huntsville, Alabama, United States
MBCCOP - Gulf Coast
🇺🇸
Mobile, Alabama, United States
Montgomery Cancer Center
🇺🇸
Montgomery, Alabama, United States
DCH Cancer Treatment Center
🇺🇸
Tuscaloosa, Alabama, United States
Foundation for Cancer Research and Education
🇺🇸
Phoenix, Arizona, United States
Providence Saint Joseph Medical Center - Burbank
🇺🇸
Burbank, California, United States
Mount Diablo Medical Center
🇺🇸
Concord, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
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University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States