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

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: Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Recurrent Fallopian Tube Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: immunohistochemistry staining method; Drug: decitabine; Other: liquid chromatography; Other: mass spectrometry; Other: enzyme-linked immunosorbent assay; Biological: NY-ESO-1 peptide vaccine; Drug: pegylated liposomal doxorubicin hydrochloride; Biological: sargramostim; Biological: incomplete Freund's adjuvant; Genetic: reverse transcriptase-polymerase chain reaction; Genetic: DNA methylation analysis

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

Study Locations

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

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

1

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	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	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		Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
Time to progression	Summarized by a Kaplan-Meier survival curve.	Up to 6 months
NY-ESO-l promoter DNA methylation using pyrosequencing		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		Days 1, 8, 15, 36, 43, 64, 71, 92, and 99

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Eisai Inc.
• Investigators: Principal Investigator: Kunle Odunsi, Roswell Park Cancer Institute

Study record dates

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: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Fallopian Tube Diseases; Ovarian Neoplasms; Recurrence; Fallopian Tube Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Decitabine; Vaccines; Azacitidine; Doxorubicin; Liposomal doxorubicin; Sargramostim; Freund's Adjuvant
• Other Study ID Numbers: I 127008; NCI-2010-00105 (Registry Identifier: CTRP (Clinical Trial Reporting Program))