<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01673217</url>
  </required_header>
  <id_info>
    <org_study_id>I 127008</org_study_id>
    <secondary_id>NCI-2010-00105</secondary_id>
    <nct_id>NCT01673217</nct_id>
    <nct_alias>NCT00887796</nct_alias>
  </id_info>
  <brief_title>Decitabine, Vaccine Therapy, and Pegylated Liposomal Doxorubicin Hydrochloride in Treating Patients With Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Peritoneal Cancer</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Roswell Park Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Roswell Park Cancer Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial is studying the side effects and best dose of decitabine when given&#xD;
      together with pegylated liposomal doxorubicin hydrochloride and vaccine therapy in treating&#xD;
      patients with recurrent ovarian epithelial cancer, fallopian tube cancer, or peritoneal&#xD;
      cancer. Drugs used in chemotherapy, such as decitabine and pegylated liposomal doxorubicin&#xD;
      hydrochloride, work in different ways to stop the growth of tumor cells, either by killing&#xD;
      the cells or by stopping them from dividing. Vaccines made from a peptide or antigen may help&#xD;
      the body build an effective immune response to kill tumor cells. Giving combination&#xD;
      chemotherapy together with vaccine therapy may kill more tumor cells&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the safety of 5-aza-2'-deoxycytidine (decitabine) in combination with&#xD;
      immunization with NYESO-I protein mixed with montanide and granulocyte-macrophage colony&#xD;
      stimulating factor (GM-CSF) in patients scheduled to receive liposomal doxorubicin for&#xD;
      recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate NY-ESO-l specific cellular and humoral immunity by determination of NY-ESO-I&#xD;
      specific antibody, CD8+ and CD4+ T-cells following immunization with NY-ESO-l protein mixed&#xD;
      with montanide and GM-CSF in combination with 5-aza-2' -deoxycytidine (decitabine) in&#xD;
      patients receiving liposomal doxorubicin for recurrent epithelial ovarian, fallopian tube or&#xD;
      primary peritoneal carcinoma.&#xD;
&#xD;
      II. To determine the impact of 5-aza-2'-deoxycytidine on NY-ESO-I specific expression,&#xD;
      NY-ESO-l promoter methylation, and global DNA methylation.&#xD;
&#xD;
      III. To compare the time to progression (ttp) for the proposed therapy with the ttp for&#xD;
      standard therapy (historical studies).&#xD;
&#xD;
      OUTLINE: This is a dose escalation study of decitabine.&#xD;
&#xD;
      Patients receive decitabine intravenously (IV) over 3 hours on day 1, pegylated liposomal&#xD;
      doxorubicin hydrochloride IV on day 8, and NY-ESO-1 peptide vaccine emulsified in incomplete&#xD;
      Freund's adjuvant and sargramostim subcutaneously on day 15. Treatment repeats every 28 days&#xD;
      for 4 courses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 6 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>April 2009</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">October 2011</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Estimated with a one-sided, 95%, Wilson score binomial confidence interval.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Will be summarized by quartiles. Also, confidence intervals will be constructed for the median and the mean.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NY-ESO-l expression using Q-RT-PCR and IHC</measure>
    <time_frame>Days 1, 8, 15, 36, 43, 64, 71, 92, and 99</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression</measure>
    <time_frame>Up to 6 months</time_frame>
    <description>Summarized by a Kaplan-Meier survival curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NY-ESO-l promoter DNA methylation using pyrosequencing</measure>
    <time_frame>Days 1, 8, 15, 36, 43, 64, 71, 92, and 99</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global genomic DNA methylation using liquid chromatography-mass spectrometry (LC-MS) and LINE-l pyrosequencing</measure>
    <time_frame>Days 1, 8, 15, 36, 43, 64, 71, 92, and 99</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Recurrent Fallopian Tube Cancer</condition>
  <condition>Recurrent Ovarian Epithelial Cancer</condition>
  <condition>Recurrent Primary Peritoneal Cavity Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>decitabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>5-aza-dCyd</other_name>
    <other_name>5AZA</other_name>
    <other_name>DAC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>NY-ESO-1 peptide vaccine</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>ESO-1 Peptide Vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pegylated liposomal doxorubicin hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>CAELYX</other_name>
    <other_name>Dox-SL</other_name>
    <other_name>DOXIL</other_name>
    <other_name>doxorubicin hydrochloride liposome</other_name>
    <other_name>LipoDox</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>sargramostim</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>GM-CSF</other_name>
    <other_name>Leukine</other_name>
    <other_name>Prokine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>incomplete Freund's adjuvant</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>IFA</other_name>
    <other_name>ISA-51</other_name>
    <other_name>Montanide ISA 51</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>immunohistochemistry staining method</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>immunohistochemistry</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>liquid chromatography</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>LC</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>mass spectrometry</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>reverse transcriptase-polymerase chain reaction</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>RT-PCR</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>laboratory biomarker analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>DNA methylation analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>enzyme-linked immunosorbent assay</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (chemotherapy and vaccine therapy)</arm_group_label>
    <other_name>ELISA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with relapsed epithelial ovarian cancer (including fallopian tube and primary&#xD;
             peritoneal cancer) who will receive liposomal doxorubicin as salvage therapy for&#xD;
             recurrent disease&#xD;
&#xD;
          -  Patients may have received up to four previous lines of chemotherapy&#xD;
&#xD;
          -  The relapse may be defined by an increase in CA125; there may or may not be either&#xD;
             measurable or symptomatic disease&#xD;
&#xD;
          -  Any human leukocyte antigen (HLA) type&#xD;
&#xD;
          -  No requirement for tumor expression of NY-ESO-1&#xD;
&#xD;
          -  Karnofsky performance status of &gt; 70%&#xD;
&#xD;
          -  Not previously treated with doxorubicin&#xD;
&#xD;
          -  Life expectancy &gt;= 6 months&#xD;
&#xD;
          -  Hematology and biochemistry laboratory results within the limits normally expected for&#xD;
             the patient population, without evidence of major organ failure&#xD;
&#xD;
          -  No immunodeficiency&#xD;
&#xD;
          -  Have been informed of other treatment options&#xD;
&#xD;
          -  Able and willing to give valid written informed consent&#xD;
&#xD;
          -  Neutrophil count &gt;= 1.5 x 10^9&#xD;
&#xD;
          -  Platelet count &gt;= 100 x 10^9&#xD;
&#xD;
          -  Serum creatinine =&lt; 2.1 mg/dL&#xD;
&#xD;
          -  Serum bilirubin =&lt; 2 mg/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =&lt; 2.6 x upper limit&#xD;
             of normal (ULN) (normal ranges: AST 15-46 U/L; ALT 11-66 U/L)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Metastatic disease to the central nervous system for which other therapeutic options,&#xD;
             including radiotherapy, may be available&#xD;
&#xD;
          -  Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding&#xD;
             disorders)&#xD;
&#xD;
          -  History of autoimmune disease (e.g., thyroiditis, lupus) except vitiligo&#xD;
&#xD;
          -  Concomitant systemic treatment with corticosteroids, anti-histamine or non-steroidal&#xD;
             anti-inflammatory drugs; specific CQX-2 inhibitors are permitted&#xD;
&#xD;
          -  Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing&#xD;
             of study agent (6 weeks for nitrosoureas)&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) positivity&#xD;
&#xD;
          -  Known allergy or history of life threatening reaction to GM-CSF&#xD;
&#xD;
          -  Myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or&#xD;
             transient ischemic attack, chest pain or shortness of breath with activity, or other&#xD;
             heart conditions being treated by a doctor&#xD;
&#xD;
          -  Participation in any other clinical trial involving another investigational agent&#xD;
             within 4 weeks prior to first dosing of study agent&#xD;
&#xD;
          -  Mental impairment that may compromise the ability to give informed consent and comply&#xD;
             with the requirements of the study&#xD;
&#xD;
          -  Lack of availability of a patient for immunological and clinical follow-up assessment&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kunle Odunsi</last_name>
    <role>Principal Investigator</role>
    <affiliation>Roswell Park Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>August 22, 2012</study_first_submitted>
  <study_first_submitted_qc>August 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 27, 2012</study_first_posted>
  <last_update_submitted>July 27, 2022</last_update_submitted>
  <last_update_submitted_qc>July 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
    <mesh_term>Decitabine</mesh_term>
    <mesh_term>Azacitidine</mesh_term>
    <mesh_term>Vaccines</mesh_term>
    <mesh_term>Sargramostim</mesh_term>
    <mesh_term>Freund's Adjuvant</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01673217
org study id: I 127008
secondary id: NCI-2010-00105
nct id: NCT01673217
nct alias: NCT00887796
lead sponsor: 
collaborator: 
has dmc: No
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0
time frame: Up to 6 months
description: Estimated with a one-sided, 95%, Wilson score binomial confidence interval.
measure: 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
description: Will be summarized by quartiles. Also, confidence intervals will be constructed for the median and the mean.
measure: NY-ESO-l expression using Q-RT-PCR and IHC
time frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
measure: Time to progression
time frame: Up to 6 months
description: Summarized by a Kaplan-Meier survival curve.
measure: NY-ESO-l promoter DNA methylation using pyrosequencing
time frame: Days 1, 8, 15, 36, 43, 64, 71, 92, and 99
measure: 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
arm group label: Treatment (chemotherapy and vaccine therapy)
arm group type: Experimental
description: 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.
intervention type: Drug
intervention name: decitabine
description: Given IV
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: 5-aza-dCyd
other name: 5AZA
other name: DAC
intervention type: Biological
intervention name: NY-ESO-1 peptide vaccine
description: Given SC
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: ESO-1 Peptide Vaccine
intervention type: Drug
intervention name: pegylated liposomal doxorubicin hydrochloride
description: Given IV
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: CAELYX
other name: Dox-SL
other name: DOXIL
other name: doxorubicin hydrochloride liposome
other name: LipoDox
intervention type: Biological
intervention name: sargramostim
description: Given SC
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: GM-CSF
other name: Leukine
other name: Prokine
intervention type: Biological
intervention name: incomplete Freund's adjuvant
description: Given SC
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: IFA
other name: ISA-51
other name: Montanide ISA 51
intervention type: Other
intervention name: immunohistochemistry staining method
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: immunohistochemistry
intervention type: Other
intervention name: liquid chromatography
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: LC
intervention type: Other
intervention name: mass spectrometry
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
intervention type: Genetic
intervention name: reverse transcriptase-polymerase chain reaction
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: RT-PCR
intervention type: Other
intervention name: laboratory biomarker analysis
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
intervention type: Genetic
intervention name: DNA methylation analysis
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
intervention type: Other
intervention name: enzyme-linked immunosorbent assay
description: Correlative studies
arm group label: Treatment (chemotherapy and vaccine therapy)
other name: ELISA
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kunle Odunsi
role: Principal Investigator
affiliation: Roswell Park Cancer Institute
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fallopian Tube Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Recurrence
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin
mesh term: Decitabine
mesh term: Azacitidine
mesh term: Vaccines
mesh term: Sargramostim
mesh term: Freund's Adjuvant