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.
Sponsor:
Collaborators:
Eisai Inc.
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01673217
First received: August 22, 2012
Last updated: January 10, 2014
Last verified: January 2014

August 22, 2012
January 10, 2014
April 2009
October 2011   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01673217 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
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

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • 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:
    • CAELYX
    • Dox-SL
    • DOXIL
    • 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
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.
Interventions:
  • 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
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
18
June 2013
October 2011   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01673217
I 127008, NCI-2010-00105
No
Roswell Park Cancer Institute
Roswell Park Cancer Institute
  • National Cancer Institute (NCI)
  • Eisai Inc.
Principal Investigator: Kunle Odunsi Roswell Park Cancer Institute
Roswell Park Cancer Institute
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP