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

This study has been completed.
Eisai Inc.
Information provided by (Responsible Party):
Roswell Park Cancer Institute Identifier:
First received: August 22, 2012
Last updated: January 10, 2014
Last verified: January 2014

This phase I trial is studying the side effects and best dose of decitabine when given together with pegylated liposomal doxorubicin hydrochloride and vaccine therapy in treating patients with recurrent ovarian epithelial cancer, fallopian tube cancer, or peritoneal cancer. Drugs used in chemotherapy, such as decitabine and pegylated liposomal doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from a peptide or antigen may help the body build an effective immune response to kill tumor cells. Giving combination chemotherapy together with vaccine therapy may kill more tumor cells

Condition Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 [ Time Frame: Up to 6 months ] [ Designated as safety issue: Yes ]
    Estimated with a one-sided, 95%, Wilson score binomial confidence interval.

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Time to progression [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 18
Study Start Date: April 2009
Study Completion Date: June 2013
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: decitabine
Given IV
Other Names:
  • 5-aza-dCyd
  • 5AZA
  • DAC
Biological: NY-ESO-1 peptide vaccine
Given SC
Other Name: ESO-1 Peptide Vaccine
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • Dox-SL
  • doxorubicin hydrochloride liposome
  • LipoDox
Biological: sargramostim
Given SC
Other Names:
  • GM-CSF
  • Leukine
  • Prokine
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Other: immunohistochemistry staining method
Correlative studies
Other Name: immunohistochemistry
Other: liquid chromatography
Correlative studies
Other Name: LC
Other: mass spectrometry
Correlative studies
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Name: RT-PCR
Other: laboratory biomarker analysis
Correlative studies
Genetic: DNA methylation analysis
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Name: ELISA

Detailed Description:


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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01673217

United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Sponsors and Collaborators
Roswell Park Cancer Institute
Eisai Inc.
Principal Investigator: Kunle Odunsi Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute Identifier: NCT01673217     History of Changes
Obsolete Identifiers: NCT00887796
Other Study ID Numbers: I 127008, NCI-2010-00105
Study First Received: August 22, 2012
Last Updated: January 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Histologic Type
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms
Freund's Adjuvant
Liposomal doxorubicin
Adjuvants, Immunologic
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Topoisomerase II Inhibitors
Topoisomerase Inhibitors processed this record on March 03, 2015