An Open-Label Study Of Exploratory Pharmacogenomics And Pharmacologic Effects Of Neoadjuvant Oral CCI-779 In Newly Diagnosed Prostate Cancer Patients Undergoing Radical Prostatectomy Who Have A High Risk Of Relapse
- Determine the effects of oral CCI-779 on changes in the phosphorylation state of
proteins in the mammalian target of rapamycin (mTOR) signaling pathway in the tumor
tissue of patients with newly diagnosed prostate cancer undergoing radical
- Determine the effects of this drug on changes in p70S6 kinase activity, phosphorylation
state of mTOR pathway proteins, and on global and targeted gene expression patterns in
the peripheral blood mononuclear cells (PBMCs) of these patients.
- Determine the effects of this drug on global and targeted gene expression patterns in
- Identify pharmacodynamic/pharmacogenomic surrogate markers of this drug in both tumor
tissue and PBMCs and determine if blood may be used as a surrogate tissue source for
biomarkers of drug activity in the tumor in these patients.
- Determine, preliminarily, the potential antitumor effects of this drug in these
- Determine the pharmacokinetics of this drug in these patients.
- Correlate phosphatase and tensin homolog (PTEN) gene status with the
pharmacodynamic/pharmacogenomic effects of this drug in these patients.
- Determine the effects of this drug on changes in protein expression patterns in the
plasma of these patients.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are randomized to 1
of 3 treatment arms. Patients randomized to arm III are stratified according to tumor
expression of phosphatase and tensin homolog (PTEN) gene mutations (negative vs positive).
- Arm I: Patients receive oral CCI-779 once daily for a total of 8 weeks.
- Arm II: Patients receive a higher dose of CCI-779 as in arm I.
- Arm III: Patients receive a higher dose (higher than arm II) of CCI-779 as in arm I.
Approximately 24-48 hours after the last dose of CCI-779, patients in all arms undergo
Patients are followed on day 7-10 and then at 4 weeks after study completion.
PROJECTED ACCRUAL: A total of 40 patients (5 each for arms I and II and 30 for arm III) will
be accrued for this study.
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Phosphorylation state of proteins
Charles Sawyers, MD
Jonsson Comprehensive Cancer Center
United States: Federal Government
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|