Postop Hypofractionated Radiation Therapy and LHRH in Patients With Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
Prostate cancer is the second most common cancer among Canadian men of which approximately 20-30% present with high-risk tumour characteristic. Although surgery can be curative in patients evidencing pathological high-risk disease (extracapsular extension, seminal vesicle involvement, positive surgical margins), a large proportion will develop biochemical failure within years from the surgical procedure. The failure rate is even more pronounced in those patients that present with high prostate specific antigen (PSA) levels, pT3 disease, positive margins and Gleason score ≥8 with an estimated 75% failure rate at 10 years. Post-operative radiotherapy (RT) has been shown in three randomized trials to significantly decrease the biochemical failure rate and in one of the trials a survival benefit was also seen with the addition of post-operative RT and is considered by many investigators standard therapy in patients with pathological high-risks factors even in absence of biochemical failure.

Detailed Description
-----------------
Although RT is known to potentially eradicate microscopic disease localized in the prostatic bed, the current dilemma is whether to deliver RT in the adjuvant setting (defined as the use of RT post-prostatectomy to patients at a higher risk of recurrence because of adverse pathological features prior to evidence of disease recurrence (i.e., with an undetectable PSA) or to use it as an early salvage therapy (defined as the use of RT in patients with rising PSA but no evidence of metastatic disease). There are several institutional retrospective reports on the use of RT as salvage therapy but no randomized trial has ever been completed. The best evidence available, however, supports early salvage RT as the best strategy to be used to maximize results. Our own group has shown excellent results using this approach in patients with low and intermediate risk disease and is currently exploring this approach in patients with high-risk disease. Hypofractionated RT offers a more convenient shorter course of treatment, reduces health-costs and appears to be as effective and safe as conventionally fractionated regimens. This Phase 2 trial will study the potential role of hypofractionated in the post-operative setting in patients with high-risk features with the primary objective of assessing toxicity from this approach. The use of androgen deprivation therapy in combination with RT in the primary treatment for patients with intermediate or high-risk prostate cancer is well established. The use of androgen suppression in the post-operative setting has been less explored and its definitive role has not been fully explored. This is a phase II clinical trial to assess the feasibility and overall toxicity of adding one injection of neo-adjuvant hormonal therapy starting 12 weeks before plus Hypofractionated Radiotherapy for four weeks concurrently with another injection of luteinizing hormone-releasing hormone (LHRH) analog in patients with post-operative setting in patients with high-risk features.

Official Title
-----------------
Postoperative Hypofractionated Radiation Therapy and Hormonal Therapy in Patients With Prostate Cancer: A Phase II Trial

Conditions
-----------------
Prostate Cancer

Intervention / Treatment
-----------------
* Drug: Eligard


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically proven high risk (any of the following risk factors: surgical positive margins; extra-capsular extension; seminal vesicle involvement, Gleason score >7) adenocarcinoma of the prostate after a radical prostatectomy as primary treatment (adjuvant group), with pathologically negative lymph nodes dissection or clinically negative lymph nodes by imaging [pelvic and abdominal computed tomography (CT) scan, or magnetic resonance imaging (MRI)]. Lymphadenectomy is not mandatory. Any type of prostatectomy will be permitted. For this group of patients, the PSA level at time of entry must be below 0.4 ng/ml Histologically proven adenocarcinoma after a radical prostatectomy with pathologically negative lymph nodes (lymphadenectomy is not mandatory) or clinically negative lymph nodes by imaging (pelvic and abdominal CT scan, or MRI or) and evidence of biochemical failure (defined as two consecutives rises of the PSA, at any PSA level). PSA upper limit post-prostatectomy must be below 2.0 ng/ml (salvage group). Any type of prostatectomy will be permitted Negative bone metastases proven by bone scan. The use of proton emission tomography (PET) fluoride is allowed History and physical examination (including digital rectal exam) within 90 days prior of registration Adequate marrow reserve defined as: Hemoglobin ≥ 10 g/dl (patients may be transfused in order to achieve this level); Platelets ≥ 100 000 cells/mm3 and a white blood cell count of ≥ 4000 cells/ml3 AST or ALT <2 x the upper limit of normal PSA and testosterone levels within one month of registration Age ≥ 18 Zubrod Performance Status 0-1 Patients must sign a study-specific consent form Exclusion Criteria: Previous exposure to androgen deprivation Chemotherapy before or after prostatectomy Prior pelvic radiotherapy Previous malignancies (except non-melanomatous skin cancer) unless disease-free >5 years Severe, active medical condition that makes the use of any of the therapies of the study not recommended

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Post-op IMRT & hormonal therapy<br>The protocol is designed to recruit patients who have undergone prostatectomy and high risk features of the disease were found post-operatively or for patients that, after prostatectomy, a PSA rise has been documented will be enrolled in the Phase II trial. Patients will receive Eligard injection 8-12 weeks before starting radiation. The second injection is given 12 weeks after the first one concomitant with radiation therapy. | Drug: Eligard<br>* Eligard dose of 22.5mg given, 50Gy in 20 treatments of radiation therapy to start 12 weeks after first injection concurrent with second injection of Eligard<br>* Other names: Radiation;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Patient Reported Morbidity in genito-urinary and gastrointestinal toxicity | Number of Participants With Treatment-Related Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events v.5.0 (CTCAE v5.0), Change From Baseline in genito-urinary and gastrointestinal toxicity up to 12 Weeks. Assessments will be collected at baseline and at the end of radiotherapy treatment and in follow-up. | Up to 90 days after the end of radiation treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Physician-Reported Morbidity in genito-urinary and gastrointestinal toxicity | Number of Participants With Treatment-Related Adverse Events as Assessed by the CTCAE v5.0, Change From Baseline in genito-urinary and gastrointestinal toxicity up to 12 Weeks. Assessments will be collected before and at the end of radiotherapy treatment and in follow-up. For each symptom i.e., frequency, severity, the worst score experienced by the patient will be recorded. | Up to 90 days after the end of radiation treatment | 
| Late Patient-Reported Morbidity in genito-urinary and gastrointestinal toxicity | Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0, Change From Baseline in genito-urinary and gastrointestinal toxicity. Assessments will be collected at baseline and up to 5 years of follow-up. For each symptom i.e., frequency, severity, the worst score experienced by the patient will be recorded will be collected before and at the end of radiotherapy treatment and in follow-up. | from the end of radiotherapy up to five years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Eligard, Post-Operative Hypofractionation