Triptorelin and Radiation Therapy in Treating Patients Who Have Undergone Surgery for Intermediate-Risk Stage III or Stage IV Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as triptorelin, may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether giving triptorelin and radiation therapy soon after surgery or later after surgery is more effective in treating prostate cancer. PURPOSE: This randomized phase III trial is studying giving triptorelin and radiation therapy soon after surgery to see how well it works compared with giving them later after surgery in treating patients who have undergone surgery for intermediate-risk stage III or stage IV prostate cancer.

Detailed Description
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OBJECTIVES: Primary Compare the efficacy, in terms of event-free survival at 5 years, of immediate radio-hormonal therapy immediately after prostatectomy for tumor pT2, R1, pN0, or pNx versus radio-hormonal therapy at biochemical relapse. Secondary Compare the overall survival of patients treated with these regimens. Compare the metastasis-free survival of these patients. Compare the acute and late toxicities of these regimens in these patients. Compare the quality of life of patients treated with these regimens. Compare the functional dependence of patients over 75 years old. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Arm I (delayed treatment): Patients receive triptorelin intramuscularly on day 1 and then 3 months later. Patients also undergo conformal radiotherapy daily, 5 days a week, for 7 weeks. Treatment begins at biochemical relapse (PSA is more than 0.2 ng/mL) and before PSA is more than 2 ng/mL. Arm II (immediate treatment): Patients receive treatment as in arm I, but treatment begins within 6 months after surgery. After completion of study treatment, patients are followed for up to 5 years.

Official Title
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Randomized, Multicenter Study Comparing the Immediate Adjuvant Radiotherapy Associate With Hormonal Therapy of LH-RH Analogue (Decapeptyl® LP) vs Delayed Radiotherapy Until Biochemical Relapse Associated With Hormonal Therapy of LH-RH Analogue (Decapeptyl® LP) in Patients With Operable Prostate Cancer pT3 R1 pN0 or pNx at Intermediate Risk.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: triptorelin
* Procedure: adjuvant therapy
* Radiation: 3-dimensional conformal radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patient must have undergone curative surgery for a localized adenocarcinoma of the prostate pT3a, pT3b (or pT4 by reaching the bladder neck), or R1 disease (stage III or IV) PSA ≤0.1 ng/mL after prostatectomy (confirmed at 1 month) May receive treatment within 6 months after surgery Positive margins (tumoral glands in contact with contour ink) on the surgical specimen pN0 or pNx (lymph nodes resected during negative prostatectomy or lymph nodes not resected) No current clinical or biochemical progressive disease Life expectancy ≥10 years Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Patient must be affiliated to the social security system Patient must have received the information sheet and signed the consent form Exclusion criteria: Patient with prostate cancer other than adenocarcinoma Gleason score ≥8 and with seminal vesicles involved pN1 disease (Histologically confirmed nodal invasion during initial lymph node resection) pT2 disease Prior surgical or chemical castration Prior hormonal therapy Prior radiotherapy within 3 months after radical prostatectomy Prior pelvic radiotherapy No history of cancer (except basal cell skin cancer) within 5 years of surgery No known severe hypertension uncontrolled by appropriate therapy (≥160 mm Hg systolic and/or ≥90 mm Hg diastolic) Known hypersensitivity to gonadotropin-releasing hormone or its analogs Contraindication to intramuscular injection Concurrent participation in another interventional study Patients under protective custody or guardianship, unable to comply with the specific requirements of the study or unable to understand the purpose of the study

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 |
| --- | --- |
| Other: A Relapse<br>Radiotherapy and Hormonotherapy only if relapse | Drug: triptorelin<br> <br> * Other names: Decapeptyl;Procedure: adjuvant therapy<br> <br> Radiation: 3-dimensional conformal radiation therapy<br> <br> |
| Experimental: B Immediate treatment<br>Radiotherapy and Hormonotherapy at randomization | Drug: triptorelin<br> <br> * Other names: Decapeptyl;Procedure: adjuvant therapy<br> <br> Radiation: 3-dimensional conformal radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | The event-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse (clinical progression, biochemical progression, death) | From randomization to disease progression or death, up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | The overall survival is the length of time from randomization that patients enrolled in the study are still alive. | From randomization to death from any cause, up to 10 years | 
| Metastases-free survival | The metastases-free survival is the length of time during and after the treatment for cancer that a patient is still alive and the cancer has not spread to other parts of the body. | From randomization to metastases onset, up to 10 years | 
| Acute or chronic toxicity | The National Cancer Institute-Common Terminology Criteria for Adverse Events version 3 (NCI-CTCAE v3.0) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale will assess the severity of sensory neuropathic disorders, this derivative into 5 grades determined by the investigator. | Throughout study completion, up to 10 years | 
| Quality of life questionnaire - Core 30 (QLQ-C30) | Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. | At baseline, 2 years, and 5 years | 
| Quality of Life Questionnaire - Prostate Cancer Module (QLQ-PR25) | This EORTC prostate cancer specific questionnaire is intended to supplement the QLQ-C30. The prostate cancer module is a 25-item questionnaire designed for use among patients with localized and metastatic prostate cancer. It includes subscales assessing urinary symptoms (9 items), bowel symptoms (4 items), treatment-related symptoms (6 items), and sexual functioning (6 items). Using a 4-point Likert scale (1 = not at all, 2 = a little, 3 = quite a bit, and 4 = very much), patients indicate the degree to which they have experienced symptoms. | At baseline, 2 years, and 5 years | 
| Functional dependence in patients over 75 years old | The Lawton Instrumental Activities of Daily Living (IADL) Scale is a self-reported questionnaire to assess independent living skills for older adults. This questionnaire, composed of 31 questions organized into 8 domains (ability to use telephone, shopping, food preparation, housekeeping, laundering, mode of transportation, responsibility for own medications, and ability to handle finances), is designed to identify improvement or deterioration of a person functioning over time. Each domain is scored 0-1 for a summary score ranging from 0 (low function, dependent) to 8 (high function, independent). | At baseline, 2 years, and 5 years | 

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