RADICALS - Radiotherapy and Androgen Deprivation In Combination After Local Surgery

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Androgens can cause the growth of prostate cancer cells. Androgen deprivation therapy, such as goserelin, leuprolide, or bicalutamide, may lessen the amount of androgens made by the body. Giving radiation therapy together with androgen deprivation therapy may kill more prostate cancer cells. PURPOSE: This randomized phase III trial is studying how well giving radiation therapy together with androgen deprivation therapy works in treating patients who have undergone surgery for prostate cancer.

Detailed Description
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OBJECTIVES: Assess the timing of radiotherapy and the use of hormone therapy in conjunction with post-operative radiotherapy. Determine the impact of radiotherapy on general quality of life, sexual function, urinary function, and bowel function. Determine the impact of duration of hormone therapy on general quality of life and sexual function. OUTLINE: This is a multicenter study. Patients requiring immediate radiotherapy (RT) are assigned to arm I; patients do not require immediate RT are assigned to arm II. Patients for whom the need of immediate post-operative radiotherapy are uncertain undergo radiotherapy timing randomization within 3 months after surgery and are randomized to 1 of 2 radiotherapy arms. Arm I (immediate RT): Within 2 months after randomization, patients undergo radiotherapy to the prostate bed once a day, 5 days a week, for 4 (20 fractions total) or 6.5 weeks (33 fractions total). They may also undergo radiotherapy to the pelvic lymph nodes once a day, 5 days a week, for 4.5 weeks (23 fractions total) at the investigator's discretion. Arm II (early salvage RT in case of PSA failure): Within 2 months of confirmation of post-operative biochemical failure, patients undergo radiotherapy as in arm I. Patients undergoing immediate RT and patients who eventually need early salvage RT undergo hormone therapy duration randomization before the administration of post-operative radiotherapy. Patients are randomized to 1 of 3 hormone therapy arms. Arm III (no hormone therapy): Patients do not receive hormone therapy. They receive post-operative RT alone as described above in arm I or II. Arm IV (RT and short-term hormone therapy): Beginning approximately 2 months prior to the start of RT, patients receive hormone therapy for 6 months. Hormone therapy* may comprise of LHRH agonist (gonadotrophin-releasing hormone analogue [GnRHa] [e.g., goserelin or leuprolide acetate]) or bicalutamide daily. Arm V (RT and long-term hormone therapy): Beginning approximately 2 months prior to the start of RT, patients receive hormone therapy for 24 months. Hormone therapy* may comprise of LHRH agonist (gonadotrophin-releasing hormone analogue [GnRHa] [e.g., goserelin or leuprolide acetate]) or bicalutamide daily. NOTE: *For Canadian patients, hormonal therapy will consist of LHRH analog (leuprolide acetate) therapy only. Treatment continues in the absence of disease progression or unacceptable toxicity. Quality of life is assessed using self-administered questionnaires at baseline and 1, 5, and 10 years after randomization. Health economics information is also collected via patient-administered questionnaires (EQ-5D) at baseline and at 1, 5 and 10 years after randomization. After completion of study treatment, patients are followed for 7 years.

Official Title
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Radiation Therapy and Androgen Deprivation Therapy in Treating Patients Who Have Undergone Surgery for Prostate Cancer (RADICALS)

Conditions
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Gastrointestinal Complications, Prostate Cancer, Sexual Dysfunction, Urinary Complications

Intervention / Treatment
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* Drug: bicalutamide
* Drug: goserelin acetate
* Drug: leuprolide acetate
* Procedure: adjuvant therapy
* Procedure: quality-of-life assessment
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Inclusion criteria: Diagnosis of nonmetastatic adenocarcinoma of the prostate Must have undergone radical prostatectomy Post-operative serum prostate-specific antigen (PSA) < 0.4 ng/mL No post-operative biochemical failure, defined as EITHER two consecutive rises in PSA and final PSA > 0.1 ng/mL OR three consecutive rises in PSA (for patients undergoing hormone therapy duration randomization) Exclusion criteria: Known distant metastases from prostate cancer PSA > 5 ng/mL at the time of hormone randomization (for patients undergoing hormone therapy duration randomization) PATIENT CHARACTERISTICS: No other active malignancy likely to interfere with protocol treatment or follow-up PRIOR CONCURRENT THERAPY: Inclusion criteria: See Disease Characteristics Co-enrollment to other trials is permitted, providing this does not interfere with the outcome measures 5-α reductase inhibitors, soya, selenium, and vitamin E are acceptable non-trial therapies Exclusion criteria: Prior hormone therapy Bilateral orchidectomy Prior pelvic radiotherapy Neoadjuvant treatment Other concurrent therapies for prostate cancer (e.g., estrogens or cytotoxic chemotherapy) prior to disease progression

Ages Eligible for Study
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Minimum Age: 0 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: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RADICALS-RT: Early RT<br> | Procedure: adjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: RADICALS-RT: Salvage RT<br> | Procedure: adjuvant therapy<br> <br> Procedure: quality-of-life assessment<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: RADICALS-HD: Radiotherapy Alone<br> | Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: RADICALS-HD: Radiotherapy + 6 months<br> | Drug: bicalutamide<br> <br> Drug: goserelin acetate<br> <br> Drug: leuprolide acetate<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |
| Experimental: RADICALS-HD: Radiotherapy + 24 months<br> | Drug: bicalutamide<br> <br> Drug: goserelin acetate<br> <br> Drug: leuprolide acetate<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-specific survival (i.e., death due to prostate cancer) (RADICALS-HD) |  | up 12 years | 
| Freedom from distant metastases (any distance metastases or prostate cancer death) (RADICALS-RT) |  | up 12 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from treatment failure |  | up 12 years | 
| Clinical progression-free survival |  | up 12 years | 
| Overall survival |  | up 12 years | 
| Non-protocol hormone therapy |  | up 12 years | 
| Treatment toxicity |  | up 12 years | 
| Patient reported outcomes - EQ5D |  | up 12 years | 
| Freedom from biochemical progression (RADICALS-RT) |  | up 12 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sexual dysfunction, urinary complications, gastrointestinal complications, adenocarcinoma of the prostate, stage I prostate cancer, stage IIB prostate cancer, stage IIA prostate cancer, stage III prostate cancer