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

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 (HRPC).

Condition	Intervention	Phase
Hormone Refractory Prostate Cancer	Drug: RAD001	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Biochemical Response Rate [ Time Frame: Patients were followed for a median of 315 days ] [ Designated as safety issue: No ]
Number of participants with 50% decline in serum PSA from baseline was pre-set as the primary measure of disease response.

Secondary Outcome Measures:

Pathologic Response [ Time Frame: Patients were followed for a median of 315 days ] [ Designated as safety issue: No ]
Number of participants with either a 50% or greater decrease in proliferation index or a 50% or greater increase in apoptotic index
Progression Free Survival [ Time Frame: Patients were followed for a median of 315 days, with the last patient censored at 1309 days. ] [ Designated as safety issue: No ]
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 [ Time Frame: Patients were followed for a median of 315 days ] [ Designated as safety issue: No ]
Functional extent of mTOR inhibition by changes in the phosphorylation status of pS6 in prostate tumors.
Clinical Response [ Time Frame: Patients were followed for a median of 315 days ] [ Designated as safety issue: No ]
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

Enrollment:	35
Study Start Date:	August 2005
Study Completion Date:	January 2010
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: RAD001 RAD001 at a dose of 10 mg PO daily	Drug: RAD001 RAD001 at a dose of 10 mg PO daily Other Name: Everolimus

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 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

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, 27710

Sponsors and Collaborators

Daniel George

Novartis Pharmaceuticals

Investigators

Principal Investigator:

Daniel J George, MD

Duke University Health System

More Information

No publications provided

Responsible Party:	Daniel George, Associate Professor of Medicine, Duke University Medical Center
ClinicalTrials.gov Identifier:	NCT00629525 History of Changes
Other Study ID Numbers:	Pro00009495 (7521)
Study First Received:	February 27, 2008
Results First Received:	January 4, 2013
Last Updated:	April 16, 2013
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Additional relevant MeSH terms:

Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Everolimus
Sirolimus
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on June 18, 2013