RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

Phase 2

Completed

Conditions: Hormone Refractory Prostate Cancer

Interventions: Drug: RAD001

Registration Number: NCT00629525

Lead Sponsor: Daniel George, MD

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
RAD001	RAD001	RAD001 at a dose of 10 mg PO daily

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival	Patients were followed for a median of 315 days, with the last patient censored at 1309 days.	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.
Molecular Response	Patients were followed for a median of 315 days	Functional extent of mTOR inhibition by changes in the phosphorylation status of pS6 in prostate tumors.
Pathologic Response	Patients were followed for a median of 315 days	Number of participants with either a 50% or greater decrease in proliferation index or a 50% or greater increase in apoptotic index
Clinical Response	Patients were followed for a median of 315 days	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