Azacitidine With Carboplatin and Paclitaxel for Newly Diagnosed Ovarian Cancer
This is a clinical trial for women with newly diagnosed ovarian cancer. The purpose of this study is to determine if the addition of a drug called azacitidine (Vidaza®)when added to carboplatin and paclitaxel will change the genetic material of the tumor so that the chemotherapy drugs work better.
The study will also determine what the maximum tolerated dose of azacitidine that may be safely used in combination with carboplatin and paclitaxel.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Neoadjuvant Azacitidine With Carboplatin and Paclitaxel for Suboptimal Newly Diagnosed Ovarian Cancer|
- 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. [ Time Frame: 15 days ] [ Designated as safety issue: Yes ]
- Secondary endpoints are disease free survival, overall survival, toxicity, quality of life as measured by the Functional Assessment of Cancer Therapy-Ovarian Cancer symptom (FOSI) index, and basic science correlate. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: Single group assignment
Patients will receive Azacitidine at 20, 40, or 75 milligrams per meter squared subcutaneous once daily for 7 days.
Azacitidine 20 milligrams per meter squared subcutaneous once daily for 7 days.Drug: Azacitidine
Azacitidine 40 milligrams per meter squared subcutaneous once daily for 7 days.Drug: Azacitidine
Azacitidine 75 milligrams per meter squared subcutaneous once daily for 7 days.
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 receive one of three different doses of Azacitidine.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00842582
|United States, Illinois|
|Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center|
|Maywood, Illinois, United States, 60153|
|Central Dupage Hospital|
|Winfield, Illinois, United States, 60190|
|Principal Investigator:||Laura Horvath, MD||Loyola University Cardinal Bernadin Cancer Center|