Radiation Therapy in Treating Patients With Stage II Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which dose of radiation therapy is more effective in treating stage II prostate cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of two different doses of specialized radiation therapy in treating patients who have stage II prostate cancer.

Detailed Description
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OBJECTIVES: Compare the overall survival of patients with stage II adenocarcinoma of the prostate treated with high- vs standard-dose three-dimensional conformal or intensity-modulated radiotherapy. Compare the freedom from prostate-specific antigen failure, disease-specific survival, local progression, and distant metastases in patients treated with these regimens. Compare the probability of tumor control and normal tissue complications in patients treated with these regimens. Compare the incidence of grade 2 or greater genitourinary and gastrointestinal acute and late toxicity in patients treated with these regimens. Compare the quality of life, including sexual function, of patients treated with these regimens. Correlate histopathologic or tumor-specific cytogenetic or chromosomal markers with cancer control outcomes in patients treated with these regimens. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to Gleason score and prostate-specific antigen (PSA) level (Gleason score 2-6, PSA ≥10 mg/mL but < 20 ng/mL vs Gleason score 7, PSA < 15 ng/mL) and radiation modality (three-dimensional conformal radiotherapy [3D-CRT] vs intensity-modulated radiotherapy [IMRT]). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo standard-dose 3D-CRT or IMRT once daily, 5 days a week, for 7.8 weeks (39 treatment days). Arm II: Patients undergo high-dose 3D-CRT or IMRT once daily, 5 days a week, for 8.8 weeks (44 treatment days). Quality of life (QOL) is assessed initially at baseline. After completion of radiotherapy, QOL is assessed every 3 months for 1 year and then every 6 months for 4 years. Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 1,520 patients (760 per treatment arm) will be accrued for this study within 5 years.

Official Title
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A Phase III Randomized Study Of High Dose 3D-CRT/IMRT Versus Standard Dose 3D-CRT/IMRT In Patients Treated For Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: 70.2 Gy 3D-CRT/IMRT
* Radiation: 79.2 Gy 3D-CRT/IMRT


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate Clinical stage T1b-T2b Meets one of the following criteria: Gleason score 2-6 AND prostate-specific antigen (PSA) ≥ 10 ng/mL but < 20 ng/mL Gleason score 7 AND PSA < 15 ng/mL No regional lymph node involvement No distant metastases PATIENT CHARACTERISTICS: Age: Any age Performance status: Zubrod 0-1 Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: No other invasive malignancy within the past 5 years except localized basal cell or squamous cell skin cancer No other major medical or psychiatric illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy No concurrent cytotoxic chemotherapy Endocrine therapy: At least 3 months since prior finasteride No other prior hormonal therapy, including: Luteinizing hormone-releasing hormone agonists (e.g., goserelin or leuprolide) Antiandrogens (e.g., flutamide or bicalutamide) Estrogens (e.g., diethylstilbestrol) No concurrent (neoadjuvant or adjuvant) hormonal therapy Radiotherapy: No prior pelvic irradiation or brachytherapy Surgery: No prior radical surgery (prostatectomy) or cryosurgery for prostate cancer No prior surgical castration (bilateral orchiectomy) Other: At least 3 months since prior finasteride or phytoestrogen preparation (PC-SPES)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 70.2 Gy<br>70.2 Gy 3D-CRT/IMRT | Radiation: 70.2 Gy 3D-CRT/IMRT<br>* Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 70.2 Gy in 39 Fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 70.2 Gy.<br>* Other names: intensity modulated radiation therapy;|
| Experimental: 79.2 Gy<br>79.2 Gy 3D-CRT/IMRT | Radiation: 79.2 Gy 3D-CRT/IMRT<br>* Radiation will be delivered via 3D conformal radiation therapy (3D-CRT) or intensity modulated radiation therapy (IMRT) in 1.8 Gy minimum dose fractions to a total of 79.2 Gy in 44 fractions. All fields treated once daily, five fractions per week. No more than 2% of the planning target volume and none of the clinical target volume may receive less than 79.2 Gy.<br>* Other names: intensity modulated radiation therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | 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 know to be alive are censored at date of last contact. | From randomization to date of failure (death) or last follow-up. Analysis occurs after all patients have been potentially followed for 8 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate-specific Antigen (PSA) Failure by American Society for Therapeutic Radiology and Oncology (ASTRO) Definition | Failure is defined as having 3 consecutive elevations of post-treatment PSA or starting hormones after one or more elevations in post-treatment PSA but before three consecutive elevations were documented. The failure day date was the midpoint between last non-rising PSA and first PSA rise. Failure rates are estimated by the cumulative incidence method. Patients last known to be alive are censored at date of last contact. | From randomization to date of failure (3 consecutive rises) or death or last follow-up. Analysis occurred after patients have been potentially followed for 5 years. | 
| Disease Specific Survival | Survival time is defined as time from randomization to the date of death due to prostate cancer and is estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact. Death due to prostate cancer was defined as primary cause of death certified as due to prostate cancer, or death in association with any of the following conditions: Further clinical tumor progression occurring after initiation of salvage anti-tumor therapy, a rise (that exceeds 1.0 ng/ml) in the serum PSA level on at least two consecutive occasions that occurred during or after salvage androgen suppression therapy, or disease progression in the absence of any anti-tumor therapy. | From randomization to date of failure (death due to prostate cancer) or death from other cause or last follow-up. Analysis occurs at the same time as the primary endpoint. | 
| Local Progression | Failure time is defined as time from randomization to the date of progression (increase in palpable abnormality), failure of regression of the palpable tumor by two years, and redevelopment of a palpable abnormality after complete disappearance of previous abnormalities. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact. | From randomization to date of failure (local progression) or death or last follow-up. Analysis occurs at the same time as the primary endpoint. | 
| Distant Metastases | Failure time is defined as time from randomization to the date of documented regional nodal recurrence or development of distant disease. Failure rates are estimated by the cumulative incidence method. Patients last know to be alive are censored at date of last contact. | From randomization to date of failure (distant metastasis) or death or last follow-up. Analysis occurs at the same time as the primary endpoint. | 
| Grade 2 or Greater Genitourinary or Gastrointestinal Toxicity | Rate of acute 2+ grade genitourinary(GU)/gastrointestinal(GI) toxicity graded by Common Toxicity Criteria (CTC) version 2.0 | From the start of treatment to 90 days. Analysis occurs at the same time as the primary endpoint | 
| Percentage of Participants With Erectile Disfuction at 12 Months | The International Index of Erectile Function Questionnaire (IIEF) is the primary measure for erectile function (ED). IIEF question number 1 (How often were you able to get an erection during sexual activity?) is scored from: none/almost never (response 0-1) or < half the time (response 2-3) to most times/almost always/always (response 4-5). A response of 0 to 3 on question number 1 of the IIEF is considered erectile dysfunction. | Twelve months from randomization | 
| Number of Participants With Improved, Stable, and Declined Spitzer Quality of Life Index (SQLI) at 12 Months | The SQLI measures quality of life for patients with cancer and other chronic diseases. Possible scores range from 0 to 10, with higher scores indicating a better outcome. Change from Baseline is defined as 12 month SQLI - baseline SQLI and is classified as follows: Improvement: when change >= to the standard error of measurement with reliability quotient of 0.5 (SEM); Stable: when -SEM < change < SEM; Declined: when change <= SEM. | Baseline and 12 months from randomization | 
| Quality Adjusted Survival by SQLI |  | From randomization to 5 years. | 
| Tumor Control Probability |  | From randomization to date of failure (tumor progression) or last follow-up. Analysis can occur any time after the primary endpoint analysis. | 
| Normal Tissue Complication Probability |  | From randomization to last follow-up. Analysis can occur any time after the primary endpoint analysis. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adenocarcinoma of the prostate, stage IIB prostate cancer, stage IIA prostate cancer