Everolimus in Treating Patients With Newly Diagnosed Localized Prostate Cancer

Phase 2

Terminated

Conditions: Prostate Cancer

Interventions: Drug: Everolimus
Procedure: conventional surgery

Registration Number: NCT00526591

Lead Sponsor: Jorge A. Garcia, MD

Brief Summary: RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving everolimus before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This randomized phase II trial is studying the side effects and how well everolimus works in treating patients with newly diagnosed localized prostate cancer.

Detailed Description: OBJECTIVES:

Primary

* To determine the clinical effects of everolimus, in terms of pathologic response (i.e., histologic P0, margin status, or capsular penetration) and surgical outcome, in patients with newly diagnosed localized prostate cancer treated with two different doses of everolimus prior to radical prostatectomy.

* To evaluate the safety and tolerability of this drug in these patients.

Secondary

* To determine the effect of this drug on prostate-specific antigen (PSA) levels in these patients.

* To determine the effect of this drug on levels of expression of PTEN, Akt, phospho-mTOR (i.e., Se2448), phospho-p70 S6 kinase (i.e., Thre389), phospho-Smad3 (i.e., Ser433/435), phospho-Smads 1/5 (i.e., Ser463/465), AR, and TUNEL in these patients.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive low-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.

* Arm II: Patients receive high-dose oral everolimus once daily for up to 8 weeks in the absence of unacceptable toxicity.

Within 7 days after the last dose of everolimus, all patients undergo radical prostatectomy with bilateral pelvic lymphadenectomy.

Tumor biopsy specimens acquired prior to treatment and prostate tumor tissue acquired at the time of radical prostatectomy are evaluated for biomarker correlative studies. Tissue samples are assessed by immunohistochemistry (IHC) and tissue microarray analysis for expression of cellular and molecular biomarkers (i.e., p-S6, p-4E-BP1, and p-Akt) that correlate with response. Prostatectomy specimens are also assessed by pathologic analysis for histopathologic response (i.e., pathologic stage, Gleason score, margin status, and tumor size).

After completion of study therapy, patients are followed at 6 weeks.

Recruitment & Eligibility

Status: TERMINATED

Sex: Male

Target Recruitment: 17

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Low-dose Everolimus Cohort	conventional surgery	5mg Everolimus daily continuously for 8 weeks and conventional surgery
High-dose Everolimus Cohort	conventional surgery	10mg Everolimus daily continuously for 8 weeks and conventional surgery
Low-dose Everolimus Cohort	Everolimus	5mg Everolimus daily continuously for 8 weeks and conventional surgery
High-dose Everolimus Cohort	Everolimus	10mg Everolimus daily continuously for 8 weeks and conventional surgery

Primary Outcome Measures

Name	Time	Method
Proportion of Patients Who Are P0 (i.e., no Clinically Detectable Tumor in the Pathologic Specimen) at Surgery	After 8 weeks of therapy at the time of prostatectomy	Specimens are fixed in formalin for 24 hours.Specimens are the cut at 3 mm intervals perpendicular to the rectal surface and the sections are examined grossly and microscopically on routine Hematoxylin and Eosin stain (H\&E) (pathologic complete response or P0) will be defined as responders.
Toxicity Profile of Each Dose (Number of Patients With Worst Grade Toxicity)	at daily dose for 8 weeks	Toxicity will be assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 3.0 (CTCAEv3.0)

Secondary Outcome Measures