Intensity-Modulated Radiation Therapy in Treating Patients With Localized 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 schedule of intensity-modulated radiation therapy is more effective in treating patients with prostate cancer. PURPOSE: This randomized phase III trial is studying the side effects of three schedules of intensity-modulated radiation therapy and compares how well they work in treating patients with localized prostate cancer.

Detailed Description
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OBJECTIVES: Determine the safety and efficacy of conventional vs hypofractionated high-dose intensity-modulated radiotherapy in patients with localized prostate cancer. Determine the side effects of these regimens in these patients. Determine whether hypofractionated radiotherapy schedules will improve the therapeutic ratio by either improving tumor control or reducing normal tissue side effects. Compare acute and late treatment-related gastrointestinal and urological toxicity in these patients. Determine different prostate-specific antigen-related endpoints for local failure and distant metastases. Extend the database of patients treated to escalated doses with dose-volume histograms (DVHs) of normal tissues at risk and relate these to common toxicity endpoints. Develop a model to estimate normal tissue complication probability (NTCP) of rectum and bladder for hypofractionated as well as conventional dose-escalated radiotherapy schedules. OUTLINE: This is a multicenter, randomized, pilot study. Patients are stratified according to risk of seminal vesicle involvement (low-risk vs moderate-risk or high-risk). Hormone therapy: Patients receive androgen-deprivation therapy comprising an injection of luteinizing hormone-releasing hormone (LHRH) agonist once monthly for 3-6 months and oral cyproterone acetate beginning the week before the first LHRH agonist injection and continuing for at least 2 weeks after each LHRH agonist injection. Within one week after the last LHRH agonist injection, patients proceed to radiotherapy. Radiotherapy: Patients are randomized to 1 of 3 treatment arms. Arm I: Patients undergo conventional high-dose intensity-modulated radiotherapy (IMRT) in 37 fractions over 7.5 weeks. Arm II: Patients undergo hypofractionated high-dose IMRT in 20 fractions over 4 weeks. Arm III: Patients undergo hypofractionated high-dose IMRT in 19 fractions over 3.8 weeks. In all arms, treatment continues in the absence of unacceptable toxicity. Quality of life is assessed periodically during study treatment. After completion of study treatment, patients are followed periodically for up to 15 years. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 2,163 patients will be accrued for this study.

Official Title
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Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy for Prostate Cancer: CHHIP

Conditions
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Prostate Cancer

Intervention / Treatment
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* Radiation: conventional radiotherapy 74 Gy delivered in 37 fractions
* Radiation: hypofractionated radiation therapy 60 Gy in 20 fractions
* Radiation: hypofractionated radiation therapy 57 Gy in 19 fractions


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the prostate, meeting the following criteria: Clinical stage T1b-T3a, N0, M0 Locally confined disease Previously untreated disease Prostate-specific antigen (PSA) ≤ 30 ng/mL Estimated risk of seminal vesicle involvement < 30% Estimated risk of seminal vesicle involvement is defined as PSA + ([Gleason score - 6] x 10) (i.e., if Gleason score ≤ 6, then PSA must be ≤ 30 ng/mL; if Gleason score = 7, then PSA must be < 20 ng/mL; if Gleason score = 8, then PSA must be < 10 ng/mL; if Gleason score = 9 or 10 patient is ineligible) PATIENT CHARACTERISTICS: WHO performance status 0 or 1 Life expectancy > 10 years (5 years for patients with poorly differentiated cancers) WBC > 4,000/mm^3 Hemoglobin > 11g/dL Platelet count > 100,000/mm^3 No other active malignancy within the past 5 years except basal cell carcinoma No hip prosthesis or fixation that would interfere with standard radiation beam configuration No comorbid conditions likely to impact on the advisability of radical radiotherapy (e.g., previous inflammatory bowel disease, previous colorectal surgery, significant bladder instability, or urinary incontinence) PRIOR CONCURRENT THERAPY: No prior pelvic radiotherapy No prior radical prostatectomy No prior androgen-deprivation therapy No concurrent full anticoagulation therapy with warfarin or heparin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control arm<br>conventional radiotherapy (74 Gy delivered in 37 fractions over 7·4 weeks) | Radiation: conventional radiotherapy 74 Gy delivered in 37 fractions<br> <br> |
| Experimental: Hypofractionated arm 1<br>Hypofractionated radiotherapy (60 Gy in 20 fractions over 4 weeks) | Radiation: hypofractionated radiation therapy 60 Gy in 20 fractions<br> <br> |
| Experimental: Hypofractionated arm 2<br>Hypofractionated radiotherapy (57 Gy in 19 fractions over 3·8 weeks) | Radiation: hypofractionated radiation therapy 57 Gy in 19 fractions<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to biochemical or clinical failure | Phoenix consensus guidelines as a PSA concentration greater than nadir plus 2 ng/mL. | Defined as the time from randomisation to biochemical failure or prostate cancer recurrence up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival |  | time from randomisation to any prostate cancer-related event or death from any cause up to 15 years | 
| Overall survival |  | Time from randomisation to death from any cause up to 15 years | 
| Development of metastases |  | Time from randomisation to development of metastases up to 15 years | 
| Recommencement of hormonal treatment for disease recurrence |  | Time from randomisation to recommencement of hormone treatment for disease recurrence up to 15 years | 
| Acute and late side-effects |  | Peak and week 18 bowel and bladder side-effects | 

 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, stage III prostate cancer