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RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

Primary Purpose

Hormone Refractory Prostate Cancer

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

RAD001

About this trial

This is an interventional treatment trial for Hormone Refractory Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Duke University MEdical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RAD001

Arm Description

RAD001 at a dose of 10 mg PO daily

Outcomes

Primary Outcome Measures

Biochemical Response Rate

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

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 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

Functional extent of mTOR inhibition by changes in the phosphorylation status of pS6 in prostate tumors.

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

Full Information

NCT ID

NCT00629525

First Posted

February 27, 2008

Last Updated

February 12, 2015

Sponsor

Daniel George, MD

Collaborators

Novartis Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT00629525

Brief Title

RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

August 2005 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Daniel George, MD

Collaborators

Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hormone Refractory Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

35 (Actual)

8. Arms, Groups, and Interventions

Arm Title

RAD001

Arm Type

Experimental

Arm Description

RAD001 at a dose of 10 mg PO daily

Intervention Type

Drug

Intervention Name(s)

RAD001

Other Intervention Name(s)

Everolimus

Intervention Description

RAD001 at a dose of 10 mg PO daily

Primary Outcome Measure Information:

Title

Biochemical Response Rate

Description

Number of participants with 50% decline in serum PSA from baseline was pre-set as the primary measure of disease response.

Time Frame

Patients were followed for a median of 315 days

Secondary Outcome Measure Information:

Title

Pathologic Response

Description

Number of participants with either a 50% or greater decrease in proliferation index or a 50% or greater increase in apoptotic index

Time Frame

Patients were followed for a median of 315 days

Title

Progression Free Survival

Description

Time Frame

Patients were followed for a median of 315 days, with the last patient censored at 1309 days.

Title

Molecular Response

Description

Functional extent of mTOR inhibition by changes in the phosphorylation status of pS6 in prostate tumors.

Time Frame

Patients were followed for a median of 315 days

Title

Clinical Response

Description

Time Frame

Patients were followed for a median of 315 days

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Daniel J George, MD

Organizational Affiliation

Duke Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke University MEdical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Learn more about this trial

RAD001 in Patients With Metastatic, Hormone-Refractory Prostate Cancer

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