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

NCT ID: NCT01673217

Last Updated: 2022-08-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2013-06-30

Brief Summary

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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

Detailed Description

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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.

Conditions

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Recurrent Fallopian Tube Cancer Recurrent Ovarian Epithelial Cancer Recurrent Primary Peritoneal Cavity Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

decitabine

Intervention Type DRUG

Given IV

NY-ESO-1 peptide vaccine

Intervention Type BIOLOGICAL

Given SC

pegylated liposomal doxorubicin hydrochloride

Intervention Type DRUG

Given IV

sargramostim

Intervention Type BIOLOGICAL

Given SC

incomplete Freund's adjuvant

Intervention Type BIOLOGICAL

Given SC

immunohistochemistry staining method

Intervention Type OTHER

Correlative studies

liquid chromatography

Intervention Type OTHER

Correlative studies

mass spectrometry

Intervention Type OTHER

Correlative studies

reverse transcriptase-polymerase chain reaction

Intervention Type GENETIC

Correlative studies

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

DNA methylation analysis

Intervention Type GENETIC

Correlative studies

enzyme-linked immunosorbent assay

Intervention Type OTHER

Correlative studies

Interventions

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decitabine

Given IV

Intervention Type DRUG

NY-ESO-1 peptide vaccine

Given SC

Intervention Type BIOLOGICAL

pegylated liposomal doxorubicin hydrochloride

Given IV

Intervention Type DRUG

sargramostim

Given SC

Intervention Type BIOLOGICAL

incomplete Freund's adjuvant

Given SC

Intervention Type BIOLOGICAL

immunohistochemistry staining method

Correlative studies

Intervention Type OTHER

liquid chromatography

Correlative studies

Intervention Type OTHER

mass spectrometry

Correlative studies

Intervention Type OTHER

reverse transcriptase-polymerase chain reaction

Correlative studies

Intervention Type GENETIC

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

DNA methylation analysis

Correlative studies

Intervention Type GENETIC

enzyme-linked immunosorbent assay

Correlative studies

Intervention Type OTHER

Other Intervention Names

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5-aza-dCyd 5AZA DAC ESO-1 Peptide Vaccine CAELYX Dox-SL DOXIL doxorubicin hydrochloride liposome LipoDox GM-CSF Leukine Prokine IFA ISA-51 Montanide ISA 51 immunohistochemistry LC RT-PCR ELISA

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role collaborator

Roswell Park Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kunle Odunsi

Role: PRINCIPAL_INVESTIGATOR

Roswell Park Cancer Institute

Locations

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Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

Countries

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United States

Other Identifiers

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NCI-2010-00105

Identifier Type: REGISTRY

Identifier Source: secondary_id

I 127008

Identifier Type: -

Identifier Source: org_study_id

NCT00887796

Identifier Type: -

Identifier Source: nct_alias

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