Azacitidine With Carboplatin and Paclitaxel for Newly Diagnosed Ovarian Cancer

November 1, 2016 updated by: Loyola University

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 receive one of three different doses of Azacitidine.

Study Type

Interventional

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Maywood, Illinois, United States, 60153
        • Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center
      • Winfield, Illinois, United States, 60190
        • Central DuPage Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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
  • Eastern Cooperative Oncology Group (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 Upper Limit of Normal (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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Single group assignment
Patients will receive Azacitidine at 20, 40, or 75 milligrams per meter squared subcutaneous once daily for 7 days.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
15 days

Secondary Outcome Measures

Outcome Measure
Time Frame
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
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Loyola University

Collaborators

Celgene Corporation

Investigators

  • Principal Investigator: Laura Horvath, MD, Loyola University Cardinal Bernadin Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2009

Primary Completion (Actual)

March 1, 2011

Study Completion (Actual)

March 1, 2011

Study Registration Dates

First Submitted

February 11, 2009

First Submitted That Met QC Criteria

February 11, 2009

First Posted (Estimate)

February 12, 2009

Study Record Updates

Last Update Posted (Estimate)

November 2, 2016

Last Update Submitted That Met QC Criteria

November 1, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 200777

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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