Phase II Study of RAD001 in a Neoadjuvant Setting in Men With Intermediate or High Risk Prostate Cancer

NCT00657982 | Unknown Phase 2

• 1 other identifier: SHEBA-07-4616-RB-CTIL
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The mechanisms responsible for the development of hormonal refractory prostate cancer (HRPC) have been elusive. Genetic inactivation/loss of the PTEN tumor suppressor gene occurs in 30-60% of advanced prostate cancers and in 20% of the localized form. Researchers hypothesize that PTEN loss is a landmark genetic event in prostate cancer progression into the fatal HRPC form. One consequence of PTEN loss is activation of the oncogenic Akt and phosphorylation of downstream Akt targets including mTOR. mTOR controls many important cellular processes including cell cycle regulation. We propose to evaluate pharmacodynamic assessments of the mTOR inhibitor RAD001 in intermediate and high risk prostate cancer patients in the neoadjuvant setting. Patients will be admitted to 6 weeks treatment with RAD001 10 mg/day followed by either radical prostatectomy or radiotherapy combined with hormonal treatment. Immunohistochemistry with antibodies for phosphorylated p70S6K , pS6, Akt as well as antibodies for VEGF, BCL2 and PTEN in prostate cancer tissues before and after 6 weeks RAD001 treatment will be performed. Additionally, Patients will be evaluated by FDG-PET scan before (as baseline) and after RAD001 treatment. A link between mTOR signaling and glycolysis regulation was established and may provide a mechanism to assess drug-target interaction of RAD001 in prostate cancer. The secondary endpoint of the trial will be to determine the response proportion to RAD001 treatment by assessing time to biochemical failure followed by radiation therapy or radical prostatectomy. The data will be compared to a matched cohort of high and intermediate-risk prostate cancer patients admitted to the same treatments modalities without receiving RAD001.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• PET-CT

  6 weeks

Secondary Outcomes (1)

• PSA failure

  3-5 years

Study Arms (1)

1

EXPERIMENTAL

RAD001 10 BID 6 weeks before definite treatment for localized prostate cancer

Drug: RAD001

Interventions

RAD001 DRUG

10mg BID

1

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologic documentation of adenocarcinoma of prostate Gleason grade 7-10
• No evidence for lymph node or distant disease
• No prior RT to pelvis or other regions
• Age \> 18 years
• Performance status ECOG 0-1
• ANC \>1500/l
• Hemoglobin \> 9.0 g/dl
• Platelets \>100,000/l
• Total Bilirubin \<1.5 x upper limits of normal
• AST or ALT \< 3 x upper limits of normal
• Creatinine \< 1.5 x upper limits of normal
• Electrolytes within 10% of normal Range
• Cholesterol \< 300

You may not qualify if:

• Prior hormonal therapy
• Prior RT to the pelvis
• Currently active second malignancy other than non-melanoma skin cancer
• Patients who have any severe and/or uncontrolled medical conditions such as
• Unstable angina pectoris, symptomatic congestive heart failure (New York heart association grade 2 or greater failure), myocardial infarction ≤ 6 months prior to randomization, serious uncontrolled cardiac arrhythmia
• Active or uncontrolled severe infection
• Cirrhosis, chronic active hepatitis or chronic persistent hepatitis
• Severely impaired lung function
• Evidence of bleeding diathesis or coagulopathy or need of administration of full-dose anti-coagulative(s)
• Major surgical procedure, open biopsy or significant trauma within 28 days prior to day 1
• Patients with active infection, including inflammation.
• Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)
• Uncontrolled diabetes mellitus as defined by fasting serum glucose \>1.5
• Patients receiving chronic treatment with corticosteroids or another immunosuppressive agent
• Patients with a known history of HIV seropositivity

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (1)

Sheba Medical Center

Tel Litwinsky, Tel Hashomer, 52621, Israel

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: April 1, 2008
• Primary Completion: March 1, 2010
• Last Updated: January 21, 2009

Record last verified: 2009-01

Locations

IL (1)