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
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Drug: Azacitidine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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

Resource links provided by NLM:


Further study details as provided by Loyola University:

Primary Outcome Measures:
  • 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 Outcome Measures:
  • 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 ]

Estimated Enrollment: 18
Study Start Date: February 2009
Estimated Study Completion Date: March 2012
Estimated Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00842582

Locations
United States, Illinois
Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center
Maywood, Illinois, United States, 60153
Central Dupage Hospital
Winfield, Illinois, United States, 60190
Sponsors and Collaborators
Loyola University
Celgene Corporation
Investigators
Principal Investigator: Laura Horvath, MD Loyola University Cardinal Bernadin Cancer Center
  More Information

No publications provided

Responsible Party: Laura Horvath, Principal Investigator, Loyola University Chicago
ClinicalTrials.gov Identifier: NCT00842582     History of Changes
Other Study ID Numbers: 200777
Study First Received: February 11, 2009
Last Updated: March 8, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Loyola University:
Ovarian cancer
chemotherapy
azacitidine

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Azacitidine
Carboplatin
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014