Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer
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|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 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
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|