Prostate Cancer Clinical Trial
Official title:
Phase II Study of RAD001 in a Neoadjuvant Setting in Men With Intermediate or High Risk Prostate Cancer
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.
Status | Recruiting |
Enrollment | 15 |
Est. completion date | |
Est. primary completion date | March 2010 |
Accepts healthy volunteers | No |
Gender | Male |
Age group | 18 Years and older |
Eligibility |
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 anti-coagulative(s) 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 |
Allocation: Non-Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
Israel | Sheba Medical Center | Tel Hashomer |
Lead Sponsor | Collaborator |
---|---|
Sheba Medical Center |
Israel,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | PET-CT | 6 weeks | No | |
Secondary | PSA failure | 3-5 years | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05613023 -
A Trial of 5 Fraction Prostate SBRT Versus 5 Fraction Prostate and Pelvic Nodal SBRT
|
Phase 3 | |
Recruiting |
NCT05540392 -
An Acupuncture Study for Prostate Cancer Survivors With Urinary Issues
|
Phase 1/Phase 2 | |
Recruiting |
NCT05156424 -
A Comparison of Aerobic and Resistance Exercise to Counteract Treatment Side Effects in Men With Prostate Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT03177759 -
Living With Prostate Cancer (LPC)
|
||
Completed |
NCT01331083 -
A Phase II Study of PX-866 in Patients With Recurrent or Metastatic Castration Resistant Prostate Cancer
|
Phase 2 | |
Recruiting |
NCT05540782 -
A Study of Cognitive Health in Survivors of Prostate Cancer
|
||
Active, not recruiting |
NCT04742361 -
Efficacy of [18F]PSMA-1007 PET/CT in Patients With Biochemial Recurrent Prostate Cancer
|
Phase 3 | |
Completed |
NCT04400656 -
PROState Pathway Embedded Comparative Trial
|
||
Completed |
NCT02282644 -
Individual Phenotype Analysis in Patients With Castration-Resistant Prostate Cancer With CellSearch® and Flow Cytometry
|
N/A | |
Recruiting |
NCT06305832 -
Salvage Radiotherapy Combined With Androgen Deprivation Therapy (ADT) With or Without Rezvilutamide in the Treatment of Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer
|
Phase 2 | |
Recruiting |
NCT06037954 -
A Study of Mental Health Care in People With Cancer
|
N/A | |
Recruiting |
NCT05761093 -
Patient and Physician Benefit/ Risk Preferences for Treatment of mPC in Hong Kong: a Discrete Choice Experiment
|
||
Completed |
NCT04838626 -
Study of Diagnostic Performance of [18F]CTT1057 for PSMA-positive Tumors Detection
|
Phase 2/Phase 3 | |
Recruiting |
NCT03101176 -
Multiparametric Ultrasound Imaging in Prostate Cancer
|
N/A | |
Completed |
NCT03290417 -
Correlative Analysis of the Genomics of Vitamin D and Omega-3 Fatty Acid Intake in Prostate Cancer
|
N/A | |
Completed |
NCT00341939 -
Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
|
||
Completed |
NCT01497925 -
Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer
|
Phase 1 | |
Recruiting |
NCT03679819 -
Single-center Trial for the Validation of High-resolution Transrectal Ultrasound (Exact Imaging Scanner ExactVu) for the Detection of Prostate Cancer
|
||
Completed |
NCT03554317 -
COMbination of Bipolar Androgen Therapy and Nivolumab
|
Phase 2 | |
Completed |
NCT03271502 -
Effect of Anesthesia on Optic Nerve Sheath Diameter in Patients Undergoing Robot-assisted Laparoscopic Prostatectomy
|
N/A |