A Phase I Clinical Trial of NY-ESO-1 Protein Immunization in Combination With 5-AZA-2'-Deoxycytidine (Decitabine) in Patients Receiving Liposomal Doxorubicin for Recurrent Epithelial Ovarian or Primary Peritoneal Carcinoma
- Determine the safety of decitabine when administered in combination with NY-ESO-1
peptide vaccine (emulsified with incomplete Freund's adjuvant and sargramostim
[GM-CSF]) and pegylated liposomal doxorubicin hydrochloride in patients with recurrent
ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer.
- Evaluate NY-ESO-1-specific cellular and humoral immunity by determination of
NY-ESO-1-specific antibodies and CD8+ and CD4+ T cells in patients treated with this
- Determine the impact of decitabine on NY-ESO-1-specific expression, NY-ESO-1-promoter
methylation, and global DNA methylation.
- Compare the time to progression in patients treated with this regimen vs patients
treated with standard therapy (historical studies).
OUTLINE: This is a dose-escalation study of decitabine.
Patients receive decitabine IV over 3 hours on day 1, pegylated liposomal doxorubicin
hydrochloride IV on day 8, and NY-ESO-1 peptide vaccine emulsified with incomplete Freund's
adjuvant and sargramostim (GM-CSF) subcutaneously on day 15. Treatment repeats every 28 days
for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically to assess NY-ESO-1-specific cellular and humoral
immunity by measuring NY-ESO-1-specific antibodies by ELISA; NY-ESO-1-specific CD8+ and CD4+
T cells by IFNγ-release ELISPOT assays; and the frequency of CD4+ CD25+ FOXP3+ regulatory T
cells. Tumor tissue samples are collected periodically to assess NY-ESO-1 expression by
quantitative RT-PCR and IHC; NY-ESO-1 promoter DNA methylation by pyrosequencing; and global
genomic DNA methylation by liquid chromatography-mass spectrometry.
After completion of study therapy, patients are followed at 2 weeks and then at 6 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Toxicity as measured by NCI CTCAE v3.0 criteria
Adekunle O. Odunsi, MD, PhD
Roswell Park Cancer Institute
United States: Food and Drug Administration
|Roswell Park Cancer Institute||Buffalo, New York 14263|