RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer - Full Text View

Sponsor:	Duke University
Collaborator:	Novartis Pharmaceuticals
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00629525

Purpose

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.

Condition	Intervention	Phase
Hormone Refractory Prostate Cancer	Drug: RAD001	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Efficacy Study
Official Title:	A Single Arm, Two Center, Phase II Study of RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Everolimus

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Biochemical response rate [ Time Frame: every 4 weeks and when applicable ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pathologic response defined as either a 50% or greater decrease in proliferation index or a 50% or greater increase in apoptotic index [ Time Frame: screening and again at 4 weeks ] [ Designated as safety issue: No ]
Functional extent of mTOR inhibition by changes in the phosphorylation status of S6K and CA IX protein in prostate tumors.(Molecular response). [ Time Frame: at screening and again at 4 weeks ] [ Designated as safety issue: No ]
To identify patient subsets more likely to respond to mTOR inhibition (Predictive response) [ Time Frame: at screening and again at 4 weeks ] [ Designated as safety issue: No ]
To determine the measurable response rate to RAD001 using RECIST criteria (Clinical response) [ Time Frame: every 2 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	August 2005
Estimated Study Completion Date:	December 2009
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental RAD001	Drug: RAD001 RAD001 at a dose of 10 mg PO daily

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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 SUT 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00629525

Locations

United States, North Carolina
Duke University MEdical Center
Durham, North Carolina, United States, 27705

Sponsors and Collaborators

Duke University

Novartis Pharmaceuticals

Investigators

Principal Investigator:

Daniel J George, MD

Duke University Health System

More Information

No publications provided

Responsible Party:	Duke University Medical Center ( Daniel J George, MD )
Study ID Numbers:	7521
Study First Received:	February 27, 2008
Last Updated:	September 15, 2009
ClinicalTrials.gov Identifier:	NCT00629525 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Additional relevant MeSH terms:

Everolimus
Neoplasms
Neoplasms by Site
Immunologic Factors
Prostatic Diseases
Genital Neoplasms, Male

Physiological Effects of Drugs
Urogenital Neoplasms
Genital Diseases, Male
Immunosuppressive Agents
Prostatic Neoplasms
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 27, 2009