Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer

PRIMARY OBJECTIVES:

I. To determine the safety of 5-aza-2'-deoxycytidine (decitabine) in combination with immunization with NYESO-I protein mixed with montanide and granulocyte-macrophage colony stimulating factor (GM-CSF) in patients scheduled to receive liposomal doxorubicin for recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate NY-ESO-l specific cellular and humoral immunity by determination of NY-ESO-I specific antibody, CD8+ and CD4+ T-cells following immunization with NY-ESO-l protein mixed with montanide and GM-CSF in combination with 5-aza-2' -deoxycytidine (decitabine) in patients receiving liposomal doxorubicin for recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.

II. To determine the impact of 5-aza-2'-deoxycytidine on NY-ESO-I specific expression, NY-ESO-l promoter methylation, and global DNA methylation.

III. To compare the time to progression (ttp) for the proposed therapy with the ttp for standard therapy (historical studies).

OUTLINE: This is a dose escalation study of decitabine.

Patients receive decitabine intravenously (IV) over 3 hours on day 1, pegylated liposomal doxorubicin hydrochloride IV on day 8, and NY-ESO-1 peptide vaccine emulsified in incomplete Freund's adjuvant and sargramostim subcutaneously on day 15. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6 months.

Inclusion criteria

• Subjects with relapsed epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) who will receive liposomal doxorubicin as salvage therapy for recurrent disease
• Patients may have received up to four previous lines of chemotherapy
• The relapse may be defined by an increase in CA125; there may or may not be either measurable or symptomatic disease
• Any human leukocyte antigen (HLA) type
• No requirement for tumor expression of NY-ESO-1
• Karnofsky performance status of > 70%
• Not previously treated with doxorubicin
• Life expectancy >= 6 months
• Hematology and biochemistry laboratory results within the limits normally expected for the patient population, without evidence of major organ failure
• No immunodeficiency
• Have been informed of other treatment options
• Able and willing to give valid written informed consent
• Neutrophil count >= 1.5 x 10^9
• Platelet count >= 100 x 10^9
• Serum creatinine =< 2.1 mg/dL
• Serum bilirubin =< 2 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.6 x upper limit of normal (ULN) (normal ranges: AST 15-46 U/L; ALT 11-66 U/L)

Exclusion criteria

• Metastatic disease to the central nervous system for which other therapeutic options, including radiotherapy, may be available
• Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders)
• History of autoimmune disease (e.g., thyroiditis, lupus) except vitiligo
• Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal anti-inflammatory drugs; specific CQX-2 inhibitors are permitted
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing of study agent (6 weeks for nitrosoureas)
• Known human immunodeficiency virus (HIV) positivity
• Known allergy or history of life threatening reaction to GM-CSF
• Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, chest pain or shortness of breath with activity, or other heart conditions being treated by a doctor
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to first dosing of study agent
• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study
• Lack of availability of a patient for immunological and clinical follow-up assessment