Azacitidine With Carboplatin and Paclitaxel for Newly Diagnosed Ovarian Cancer

Sponsor

Loyola University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00842582

Collaborator

Celgene Corporation (Industry)

Enrollment

Locations

Arm

24.9

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Azacitidine Drug: Azacitidine Drug: Azacitidine	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Neoadjuvant Azacitidine With Carboplatin and Paclitaxel for Suboptimal Newly Diagnosed Ovarian Cancer

Study Start Date :

Feb 1, 2009

Actual Primary Completion Date :

Mar 1, 2011

Actual Study Completion Date :

Mar 1, 2011

Arms and Interventions

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.

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.

Outcome Measures

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. [15 days]

Secondary Outcome Measures

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. [5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola Univeristy Medical Center, Cardinal Bernardin Cancer Center	Maywood	Illinois	United States	60153
2	Central Dupage Hospital	Winfield	Illinois	United States	60190