Radiotherapy Plus Hormone Therapy in Biochemically-relapsing Prostate Cancer Patients Following Surgery

Study Overview
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Brief Summary
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As there is no prospective data on the combination of abiraterone and salvage radiotherapy, the aim of this study is to further evaluate the safety profile of abiraterone acetate plus prednisone in patients with prostate cancer who are biochemically relapsing after surgery and undergo salvage radiotherapy with 6-months LH-RH agonist. The investigators hypothesize that the toxicity profile of both treatments should not potentiate each other. This study will also provide preliminary data on the efficacy of this combination.

Official Title
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Safety and Efficacy of Radiotherapy Combined With a 6-month LH-RH Agonist and Abiraterone Hormone Therapy Treatment in Biochemically-relapsing Prostate Cancer Following Surgery

Conditions
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Biochemically-relapsing Prostate Adenocarcinoma Following Radical Prostatectomy

Intervention / Treatment
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* Drug: Abiraterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed prostate adenocarcinoma The patients should have undergone only surgery for localized prostate adenocarcinoma: pT2, pT3 or pT4 with bladder neck involvement pN0: negative lymphadenectomy at the time of prostatectomy At inclusion the patients should have no clinical signs of progressive disease and should be M0 (bone and pelvic scans). ≥ 18 years of age with life expectancy ≥ 10 years Performance Status (ECOG) ≤ 1 PSA ≤ 0.1 ng/ml after prostatectomy (dosage performed within 2 months after surgery) PSA ≥ 0.2 ng/ml et ≤ 2 ng/ml at the time of inclusion Elevation of PSA over three consecutive assays performed in the same laboratory, with a minimal interval of two months between assays, (PSA nadir level followed by two other progressive assays) At least 6 months between surgery and biochemical relapse Serum potassium ≥ 3.5 mmol/L in the 72 hours before first dose of abiraterone acetate Serum creatinine < 1.5 x ULN or a calculated creatinine clearance ≥ 60 mL/min Liver function: Serum bilirubin < 1.5 x ULN (except for patients with documented Gilbert's disease) AST and ALT < 2.5 x ULN Patients must be affiliated to a Social Security System. Patient information and written informed consent form signed for both principal and additional research Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures Exclusion Criteria: pN1: histologically-proven lymph node involvement at initial lymphadenectomy Histology other than adenocarcinoma Previous hormone therapy including prior therapy with ketoconazole or other CYP17 inhibitor(s) for prostate cancer. Patients being treated within the last 14 days prior to inclusion with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A4 (Clarithromycin, Ketoconazole, Itraconazole, Voriconazole, Ritanovir, see appendix 11) or requiring those treatments during the study Active or symptomatic viral hepatitis or chronic liver disease Surgical or chemical castration History of cancer, with the exception of basal cell carcinoma or any other cancer treated in the 5 years before inclusion and in complete remission. Previous pelvic radiotherapy Uncontrolled hypertension (defined as systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg). Patients with a history of hypertension are allowed provided blood pressure is controlled by anti-hypertensive therapy (see appendix 10 for mandatory BP measurement guidelines) Severe and moderate hepatic impairment (Child-Pugh class B and C) Patients with severe and/or uncontrolled medical disease which could compromise participation in the study, such as, but not limited to: Clinically significant heart disease as evidenced by myocardial infarction, or arterial thrombotic events in the past 6 months, severe or unstable angina, or New York Heart Association (NYHA) Class III or IV heart disease or cardiac ejection fraction measurement of < 50 % at baseline Known hypersensitivity to any of the study drugs or excipients. Galactosemia, Glucose-galactose malabsorption or lactase deficiency Patients with any psychological, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Individual deprived of liberty or placed under the authority of a tutor. Patients already included in another therapeutic trial with an experimental drug or having been given an experimental drug within a period of 30 days.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: abiraterone<br>Abiraterone acetate (three dose levels in phase I) + prednisone (10mg/day)+LHRH + Radiotherapy | Drug: Abiraterone<br>* Abiraterone acetate 1000mg/day + prednisone alone for one month before initiating the sequence of radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to determine the maximum tolerated dose and the phase II recommended dose of abiraterone acetate treatment plus prednisone and LH-RH agonist combined with prostate radiotherapy |  | within 11 weeks after Radiotherapy initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the 3-year biochemical relapse-free survival |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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abiraterone, biochemically-relapsing, prostate adenocarcinoma