Neoadjuvant Azacitidine With Carboplatin and Paclitaxel for Suboptimal Newly Diagnosed Ovarian Cancer
18 Years
N/A
Female
Ovarian Cancer
Trial Information
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.
Inclusion Criteria:
- Stage III or IV epithelial ovarian cancer, fallopian tube cancer, or primary
peritoneal cancer
- Appropriately signed and documented informed consent form, with documentation of the
informed consent process
- Age more than 18 years old
- ECOG performance status less than or equal to 2
- Life expectancy greater than 12 months
- Adequate baseline bone marrow function: absolute neutrophils count greater than 1500
cells/microliter, platelet count greater than 100,000 cells per microliter
- Adequate liver function: bilirubin than 1.5 times the upper limit of normal. Higher
levels of Bilirubin are acceptable if these can be attributed to active hemolysis or
ineffective erythropoiesis. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate
aminotransferase [AST]) or serum glutamic-pyruvic transaminase (SGPT) (alanine
aminotransferase [ALT]) levels less than or equal 2 x ULN.
- Adequate renal function: Serum creatinine levels less than or equal to 1.5 times ULN
- Patients must have ascites and be considered not candidates for upfront surgery
because of disease bulk (not because of overall health).
- Women of childbearing potential must have a negative serum pregnancy test prior to
azacitidine treatment.
- Women of childbearing potential should be advised to avoid becoming pregnant and men
should be advised to not father a child while receiving treatment with azacitidine.
Exclusion Criteria:
- Ongoing serious infection
- Neuropathy greater than grade 2 at baseline
- Major surgery within 2 weeks prior to enrollment
- Concurrent investigational treatment, antineoplastic treatment, hormonal treatment,
or radiation therapy
- Prior bone marrow transplant
- prior radiation to the pelvis
- radiation therapy for malignancy within the past 5 years
- Other malignancy within the past 5 years except non-melanoma skin cancer.
- Known or suspected hypersensitivity to azacitidine or mannitol
- Pregnant or breast feeding
- Patients with advanced malignant hepatic tumors
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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.
Outcome Time Frame:
15 days
Safety Issue:
Yes
Principal Investigator
Laura Horvath, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Loyola University Cardinal Bernadin Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
200777
NCT ID:
NCT00842582
Start Date:
February 2009
Completion Date:
March 2012
Related Keywords:
- Ovarian Cancer
- Ovarian cancer
- chemotherapy
- azacitidine
- Ovarian Neoplasms
Name | Location |
|---|---|
| Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center | Maywood, Illinois 60153 |
| Central DuPage Hospital | Winfield, Illinois 60190 |
