Azacitidine With Carboplatin and Paclitaxel for Newly Diagnosed Ovarian Cancer

This study has been terminated.
(No enrollment. Unable to recruit due to lack of eligible patients.)
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Loyola University
ClinicalTrials.gov Identifier:
NCT00842582
First received: February 11, 2009
Last updated: March 8, 2011
Last verified: March 2011

February 11, 2009
March 8, 2011
February 2009
March 2011   (final data collection date for primary 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. [ Time Frame: 15 days ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00842582 on ClinicalTrials.gov Archive Site
Secondary endpoints are disease free survival, overall survival, toxicity, quality of life with FOSI questionnaire, and basic science correlate. [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Azacitidine With Carboplatin and Paclitaxel for Newly Diagnosed Ovarian Cancer
Neoadjuvant Azacitidine With Carboplatin and Paclitaxel for Suboptimal 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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Ovarian Cancer
  • Drug: Azacitidine
    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.
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
18
March 2012
March 2011   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00842582
200777
No
Laura Horvath, Principal Investigator, Loyola University Chicago
Loyola University
Celgene Corporation
Principal Investigator: Laura Horvath, MD Loyola University Cardinal Bernadin Cancer Center
Loyola University
March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP