RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

Study Overview
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Brief Summary
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The purpose of this study is to determine the biochemical response rate (PSA) to single agent RAD001 in patients with metastatic hormone-refractory prostate cancer (HRPC).

Detailed Description
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This is a single center, Phase II study of RAD001 in men with HRPC. The study design is a straight forward, two-stage design with tumor biopsies scheduled at screening and again at 4 weeks. FLT-PET scans are performed at screening and again at day 28, following initiation of treatment in the first 10 patients. Patients are assessed for adverse events every two weeks for the first month and monthly thereafter. Patients are assessed for response by PSA every 4 weeks and when applicable, for objective response every 2 months. If 4 or more responses are seen in the first 39 patients then the study will expand to 60 patients.

Official Title
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A Single Arm, Two Center, Phase II Study of RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

Conditions
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Hormone Refractory Prostate Cancer

Intervention / Treatment
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* Drug: RAD001


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of adenocarcinoma of the prostate Clinical or radiographic evidence of metastatic disease ADT using LHRH agonist (eg leuprolide, goserelin) must continue on therapy. However, ketoconazole, estrogens, and all other forms of hormonal manipulation are not permitted on study. Evidence of disease progression on ADT as evidenced by: 2 consecutive PSA levels 50% or greater above the PSA nadir achieved on ADT and separated at least 1 week apart, or Radiographic evidence of disease progression defined by RECIST criteria and compared to prior studies on ADT. A minimum of 6 weeks has elapsed off of anti-androgen therapy without withdrawal response. A minimum of 4 weeks from any prior radiation therapy, surgery, chemotherapy or other investigational agent Biopsies will not be performed if platelet counts < 75,000/ ul, PTT, PT or INR > 1.4 times control Patients must have normal organ and marrow function as defined below: hemoglobin > 9.0g/dL absolute neutrophil count > 1,500/μl platelets > 100,000/μl total bilirubin < 1.5 X upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) < 2.5 X ULN creatinine < 1.5 X ULN total fasting cholesterol < 350 total triglycerides < 300 Patients on antilipid therapy may participate in this study. Age > 18 years ECOG performance status 0 or 1 Ability to swallow and retain oral medication Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: History of solid organ or stem cell transplantation Also, no current use of chronic immunosuppressive therapy is allowed Patients with known brain metastases (or history of brain metastases) History of HIV, hepatitis B, or hepatitis C infection Patients who have received investigational, biologic, hormonal (other than ADT), immunotherapy, or chemotherapy less than 4 weeks prior to entry on this study or have not recovered from the toxic effects of such therapy Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), symptomatic congestive heart failure (NYHC III or greater), unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT or any VT), or psychiatric illness/social situations that would limit compliance with study requirements History of malabsorption syndrome, disease significantly affecting gastrointestinal function or major resection of the stomach or small bowel that could affect absorption, distribution, metabolism or excretion of study drugs. Any unresolved bowel obstruction or diarrhea

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: RAD001<br>RAD001 at a dose of 10 mg PO daily | Drug: RAD001<br>* RAD001 at a dose of 10 mg PO daily<br>* Other names: Everolimus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical Response Rate | Number of participants with 50% decline in serum PSA from baseline was pre-set as the primary measure of disease response. | Patients were followed for a median of 315 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Response | Number of participants with either a 50% or greater decrease in proliferation index or a 50% or greater increase in apoptotic index | Patients were followed for a median of 315 days | 
| Progression Free Survival | Time in months from the start of study treatment to the date of first progression according to RECIST 1.0, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. | Patients were followed for a median of 315 days, with the last patient censored at 1309 days. | 
| Molecular Response | Functional extent of mTOR inhibition by changes in the phosphorylation status of pS6 in prostate tumors. | Patients were followed for a median of 315 days | 
| Clinical Response | The percentage of participants with a complete or partial response as defined by RECIST 1.0. Response Criteria are defined below: Complete Response: Disappearance of all target lesions Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD Progressive Disease: At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease: Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD | Patients were followed for a median of 315 days |