Everolimus, Bicalutamide, and Leuprolide Acetate in Treating Patients Undergoing Radiation Therapy For High-Risk Locally Advanced Prostate Cancer

Study Overview
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Brief Summary
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RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide and leuprolide acetate may lessen the amount of androgens made by the body. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving everolimus together with bicalutamide, leuprolide acetate, and radiation therapy may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with bicalutamide and leuprolide acetate in treating patients with high-risk locally advanced prostate cancer undergoing radiation therapy.

Detailed Description
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OBJECTIVES: Primary To assess acute and late toxicities in patients with high-risk, locally advanced prostate cancer. Secondary To assess the biochemical-free survival of these patients. To assess metastasis-free survival of these patients. To assess the overall survival of these patients. To assess the molecular characteristics of the tumor before treatment and correlate with outcomes. OUTLINE: This is a dose-escalation study of everolimus. Patients undergo radiotherapy to the prostate and seminal vesicles once daily, 5 days a week, for 7.5 weeks. Beginning the week before radiotherapy, patients receive oral bicalutamide once daily for 1 month and oral everolimus twice daily for 8.5 weeks. Beginning on the first week of radiotherapy, patients receive leuprolide acetate subcutaneously every 3 months for 2 years.

Official Title
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A Phase I Trial to Evaluate Acute and Late Toxicities of Concurrent Treatment With Everolimus (RAD001) and Radio-Hormonotherapy in High-risk Prostate Cancer.(RHOMUS)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: bicalutamide
* Drug: everolimus
* Drug: leuprolide acetate
* Radiation: external beam radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of high-risk, locally advanced prostate cancer meeting ≥ 1 of the following criteria: Clinical stage ≥ T3 Gleason score ≥ 8 PSA ≥ 20 ng/mL Previously untreated disease Non-metastatic disease as assessed by bone scan and CT scan of the thorax and abdomen Negative pelvic lymph nodes as proven by pathological analysis PATIENT CHARACTERISTICS: WHO performance status 0-1 WBC ≥ 3.5 x 10^9/L ANC ≥ 1.5 x 10^9/L Platelets normal Hemoglobin > 10 g/dL Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) Albumin ≥ 3 g/dL Serum transaminases activity ≤ 2.5 x ULN Alkaline phosphatase ≤ 2.5 x ULN Serum creatinine ≤ 1.5 x ULN Covered by national health insurance No history of previous malignant disease, except for adequately treated basal cell carcinoma of the skin No ≥ grade 3 hypercholesterolemia/hypertriglyceridemia or ≥ grade 2 hypercholesterolemia/hypertriglyceridemia with history of coronary artery disease (despite lipid-lowering treatment, if given) No uncontrolled infection No dysphagia or intestinal malabsorption No other concurrent severe and/or uncontrolled medical disease that could compromise participation in the study (i.e., uncontrolled diabetes mellitus, uncontrolled cardiac disease [unstable angina], uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within the past six months, chronic liver or renal disease, and active upper gastrointestinal tract ulceration) No history of noncompliance to medical regimens No known hypersensitivity to everolimus, sirolimus (rapamycin), or temsirolimus No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study treatment and follow-up schedule PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 30 days since prior investigational drugs More than 10 days since prior and no concurrent treatment with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A

Ages Eligible for Study
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Maximum Age: 80 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: Everolimus<br>Everolimus + radiation | Drug: bicalutamide<br> <br> Drug: everolimus<br> <br> Drug: leuprolide acetate<br> <br> Radiation: external beam radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute and late toxicities |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical-free survival |  | 1 year | 
| Metastasis-free survival |  | 1 year | 
| Overall survival |  | 1 year | 
| Pre-treatment molecular characteristics of the tumor and its correlation with outcomes |  | 1 year | 

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