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

July 27, 2022 updated by: Roswell Park Cancer Institute

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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: laboratory biomarker analysis
Correlative studies
Other: immunohistochemistry staining method
Correlative studies
Other Names:
  • immunohistochemistry
Drug: decitabine
Given IV
Other Names:
  • DAC
  • 5-aza-dCyd
  • 5AZA
Other: liquid chromatography
Correlative studies
Other Names:
  • LC
Other: mass spectrometry
Correlative studies
Other: enzyme-linked immunosorbent assay
Correlative studies
Other Names:
  • ELISA
Biological: NY-ESO-1 peptide vaccine
Given SC
Other Names:
  • ESO-1 Peptide Vaccine
Drug: pegylated liposomal doxorubicin hydrochloride
Given IV
Other Names:
  • doxorubicin hydrochloride liposome
  • LipoDox
  • Dox-SL
  • CAELYX
  • DOXIL
Biological: sargramostim
Given SC
Other Names:
  • Leukine
  • Prokine
  • GM-CSF
Biological: incomplete Freund's adjuvant
Given SC
Other Names:
  • IFA
  • ISA-51
  • Montanide ISA 51
Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Names:
  • RT-PCR
Genetic: DNA methylation analysis
Correlative studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 6 months
NY-ESO-l expression using Q-RT-PCR and IHC
Time Frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
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.
Up to 6 months
NY-ESO-l promoter DNA methylation using pyrosequencing
Time Frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
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
Days 1, 8, 15, 36, 43, 64, 71, 92, and 99

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Roswell Park Cancer Institute

Collaborators

Eisai Inc.

Investigators

  • Principal Investigator: Kunle Odunsi, Roswell Park Cancer Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

October 1, 2011

Study Completion (Actual)

June 1, 2013

Study Registration Dates

First Submitted

August 22, 2012

First Submitted That Met QC Criteria

August 22, 2012

First Posted (Estimate)

August 27, 2012

Study Record Updates

Last Update Posted (Actual)

August 1, 2022

Last Update Submitted That Met QC Criteria

July 27, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • I 127008
  • NCI-2010-00105 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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