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

Phase 2
18 Years
Open (Enrolling)
Prostate Cancer

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Trial Information

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

Newly diagnosed patients with prostate cancer, with localized untreated disease must be at
intermediate or high risk for disease relapse based on their PSA, Gleason score, and
clinical stage. Before starting treatment, a baseline radiographic evaluation with FDG-PET
and magnetic resonance imaging (MRI) will be performed. Biopsies will also be performed to
obtain fresh tissue for molecular and gene expression assays. In patients with a positive
FDG-PET scan at baseline, Treatment Day 1-14 will be with RAD001 10 mg/day alone. After
performing post-RAD001 FDG-PET evaluation, treatment Day 15 will be equivalent of Treatment
Day 1 of the trial in patients with negative FDG-PET scan at baseline.

In patients with a negative FDG-PET scan at baseline, Treatment Day 1 is the beginning of
the Phase II trial of RAD001 combined with androgen ablation treatment.

Patients will be treated with RAD001 10 mg per day combined with androgen ablation therapy
for 8 weeks depending on their ability to tolerate the drug. Radiographic and biologic
assays will be repeated after 8 weeks, at which time patients will undergo prostatectomy or
external beam radiation therapy (ERT). Second biopsy will be performed in patients admitted
to ERT They will receive RAD001 up to the day of surgery or ERT to ascertain better tissue
concentration of the drug. Gene expression profiling will also be evaluated at that time.
The primary endpoint of this study is pharmacodynamic assessments of the effects of RAD001
in prostate cancer. However, the secondary endpoints of this study will define its true
success. Specifically, the study will evaluate pharmacodynamic assessments of the effects
of RAD001 in prostate cancer using novel applications of radiology, molecular biology, and
genomics. These novel endpoints will be correlated with more established pathologic
measures, such as microvessel density, apoptotic indexes, PTEN, phospho-AKT and
phospho-p70S6K. MRI and 3-dimensional. PSA effects will also be assessed. Prostate cancer
tissues from high risk prostate cancer patients admitted to neoadjuvant androgen ablation
without RAD001 will serve as controls.

An ambitious aspect of this project is to examine gene expression alterations that occur in
these patients. It will be technically challenging to get enough tissue by needle biopsies
for gene array analysis. However, clearly, obtaining this information might be very useful
in describing the full effects of RAD001 therapy in this patient population.

Inclusion Criteria:

1. Histologic documentation of adenocarcinoma of prostate Gleason grade 7-10

2. No evidence for lymph node or distant disease

3. No prior RT to pelvis or other regions

4. Age > 18 years

5. Performance status ECOG 0-1

6. ANC >1500/l

7. Hemoglobin > 9.0 g/dl

8. Platelets >100,000/l

9. Total Bilirubin <1.5 x upper limits of normal

10. AST or ALT < 3 x upper limits of normal

11. Creatinine < 1.5 x upper limits of normal

12. Electrolytes within 10% of normal Range

13. Cholesterol < 300

Exclusion Criteria:

1. Prior hormonal therapy

2. Prior RT to the pelvis

3. Currently active second malignancy other than non-melanoma skin cancer

4. Patients who have any severe and/or uncontrolled medical conditions such as

1. 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

2. Active or uncontrolled severe infection

3. Cirrhosis, chronic active hepatitis or chronic persistent hepatitis

4. Severely impaired lung function

5. Evidence of bleeding diathesis or coagulopathy or need of administration of full-dose

6. Major surgical procedure, open biopsy or significant trauma within 28 days prior to
day 1

7. Patients with active infection, including inflammation.

8. Prior therapy with mTOR inhibitors (sirolimus, temsirolimus, everolimus)

9. Uncontrolled diabetes mellitus as defined by fasting serum glucose >1.5

10. Patients receiving chronic treatment with corticosteroids or another
immunosuppressive agent

11. Patients with a known history of HIV seropositivity

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:


Outcome Time Frame:

6 weeks

Safety Issue:



Israel: Israeli Health Ministry Pharmaceutical Administration

Study ID:




Start Date:

April 2008

Completion Date:

Related Keywords:

  • Prostate Cancer
  • Prostatic Neoplasms