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

Recurrent Ovarian Epithelial Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01673217
• Other study ID #: I 127008
• Secondary ID: NCI-2010-00105
• Status: Completed
• Phase: Phase 1
• Start date: April 2009
• Est. completion date: June 2013

Study information

• Verified date: July 2022
• Source: Roswell Park Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Other known NCT identifiers

• NCT00887796

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: June 2013
• Est. primary completion date: October 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Fallopian Tube Neoplasms
• Recurrence
• Recurrent Fallopian Tube Cancer
• Recurrent Ovarian Epithelial Cancer
• Recurrent Primary Peritoneal Cavity Cancer

Intervention

Drug:
• decitabine
Given IV

Biological:
• NY-ESO-1 peptide vaccine
Given SC

Drug:
• pegylated liposomal doxorubicin hydrochloride
Given IV

Biological:
• sargramostim
Given SC
• incomplete Freund's adjuvant
Given SC

Other:
• immunohistochemistry staining method
Correlative studies
• liquid chromatography
Correlative studies
• mass spectrometry
Correlative studies

Genetic:
• reverse transcriptase-polymerase chain reaction
Correlative studies

Other:
• laboratory biomarker analysis
Correlative studies

Genetic:
• DNA methylation analysis
Correlative studies

Other:
• enzyme-linked immunosorbent assay
Correlative studies

Locations

Country	Name	City	State
United States	Roswell Park Cancer Institute	Buffalo	New York

Sponsors (2)

Lead Sponsor	Collaborator
Roswell Park Cancer Institute	Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	NY-ESO-l expression using Q-RT-PCR and IHC		Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
Secondary	Time to progression	Summarized by a Kaplan-Meier survival curve.	Up to 6 months
Secondary	NY-ESO-l promoter DNA methylation using pyrosequencing		Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
Secondary	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