Neoadjuvant Azacitidine With Carboplatin and Paclitaxel for Suboptimal Newly Diagnosed Ovarian Cancer
Ovarian cancer is a highly chemosensitive tumor with good responses to first line
chemotherapy. The problem is the high rate of relapse, especially in advanced disease
Relapses are likely due to the presence of chemoresistant cells that escape from first line
platinum and taxane based regimens. Therefore, outcomes may be improved by adding treatment
to initial standard therapy that makes resistant cells sensitive to chemotherapy. There are
multiple targeted pathways that may achieve this goal. One promising path is epigenetics.
The reasons for this trial are multifold. First, methylation pathways have been proven in
tissue models to be integral to ovarian cancer pathogenesis. Second, cisplatin and
azacitidine are synergistic, and therefore would be promising in combination to improve
ovarian cancer outcomes by combating cisplatin resistance, which is a major cause of ovarian
cancer mortality. It has been proven that azacitidine/decitabine reverses platinum
resistance. Third, azacitidine has shown tolerable toxicity and promise in clinical trials
to date. Ideally, ovarian cancer outcomes are likely to be improved by the addition of
treatment that wipes out chemoresistant cells, thus preventing relapse.
This study is a phase I, non-randomized, dose escalation treatment study using azacitidine
in combination with intravenous chemotherapy with Paclitaxel and carboplatin.
All patients will receive the chemotherapy drugs Carboplatin and Paclitaxel. Patients will
then be randomized to recieve one of three different doses of Azactitidine.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
The primary goal is to find the lowest dose of azacitidine combined with carboplatin and Paclitaxel, at which toxicity is reasonable, and methylation changes are clinically significant (at which there is a change in gene expression.
Laura Horvath, MD
Loyola University Cardinal Bernadin Cancer Center
United States: Institutional Review Board
|Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center||Maywood, Illinois 60153|
|Central DuPage Hospital||Winfield, Illinois 60190|