Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer
|ClinicalTrials.gov Identifier: NCT01673217|
Recruitment Status : Completed
First Posted : August 27, 2012
Last Update Posted : January 13, 2014
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Fallopian Tube Cancer Recurrent Ovarian Epithelial Cancer Recurrent Primary Peritoneal Cavity Cancer||Drug: decitabine Biological: NY-ESO-1 peptide vaccine Drug: pegylated liposomal doxorubicin hydrochloride Biological: sargramostim Biological: incomplete Freund's adjuvant Other: immunohistochemistry staining method Other: liquid chromatography Other: mass spectrometry Genetic: reverse transcriptase-polymerase chain reaction Other: laboratory biomarker analysis Genetic: DNA methylation analysis Other: enzyme-linked immunosorbent assay||Phase 1|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||April 2009|
|Actual Primary Completion Date :||October 2011|
|Actual Study Completion Date :||June 2013|
Experimental: Treatment (chemotherapy and vaccine therapy)
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 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.
Other Names:Biological: NY-ESO-1 peptide vaccine
Other Name: ESO-1 Peptide VaccineDrug: pegylated liposomal doxorubicin hydrochloride
Other Names:Biological: sargramostim
Other Names:Biological: incomplete Freund's adjuvant
Other Names:Other: immunohistochemistry staining method
Other Name: immunohistochemistryOther: liquid chromatography
Other Name: LCOther: mass spectrometry
Correlative studiesGenetic: reverse transcriptase-polymerase chain reaction
Other Name: RT-PCROther: laboratory biomarker analysis
Correlative studiesGenetic: DNA methylation analysis
Correlative studiesOther: enzyme-linked immunosorbent assay
Other Name: ELISA
- Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 6 months ]Estimated with a one-sided, 95%, Wilson score binomial confidence interval.
- NY-ESO-1 specific cellular and humoral immunity as assessed by NY-ESO-1-specific CD8+ and CD4+ T cells and antibodies and frequency of CD4+ CD25+ FOXP3+ regulatory T cells [ Time Frame: Up to 6 months ]Will be summarized by quartiles. Also, confidence intervals will be constructed for the median and the mean.
- NY-ESO-l expression using Q-RT-PCR and IHC [ Time Frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99 ]
- Time to progression [ Time Frame: Up to 6 months ]Summarized by a Kaplan-Meier survival curve.
- NY-ESO-l promoter DNA methylation using pyrosequencing [ Time Frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99 ]
- Global genomic DNA methylation using liquid chromatography-mass spectrometry (LC-MS) and LINE-l pyrosequencing [ Time Frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01673217
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|Principal Investigator:||Kunle Odunsi||Roswell Park Cancer Institute|