<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/NCT03029403</url>
  </required_header>
  <id_info>
    <org_study_id>PESCO</org_study_id>
    <nct_id>NCT03029403</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of Pembrolizumab, DPX-Survivac Vaccine and Cyclophosphamide in Advanced Ovarian, Primary Peritoneal or Fallopian Tube Cancer</brief_title>
  <official_title>A Phase 2 Study of Pembrolizumab (MK-3475), DPX-Survivac Vaccine and Low Dose of Cyclophosphamide Combination in Patients With Advanced Ovarian, Primary Peritoneal or Fallopian Tube Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>ImmunoVaccine Technologies, Inc. (IMV Inc.)</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase 2 study whose purpose is to see whether the combination of of pembrolizumab,&#xD;
      DPX-Survivac vaccine and low-dose cyclophosphamide has anti-tumor activity in patients with&#xD;
      advanced epithelial ovarian, fallopian tube or primary peritoneal cancer.&#xD;
&#xD;
      DPX-Survivac is an investigational vaccine. A vaccine is a substance that is often given to&#xD;
      stimulate the body's immune system (the structure and processes in the body that protects&#xD;
      against harmful substances) to help prevent against certain diseases. DPX-Survivac is a&#xD;
      vaccine that may teach the immune system to recognize cancer cells and to kill them.&#xD;
&#xD;
      Pembrolizumab is a drug that is approved for the treatment of a certain type of melanoma (a&#xD;
      type of skin cancer) and non-small cell lung cancer. Pembrolizumab blocks the function of a&#xD;
      protein called programmed cell death receptor-1 (PD-1). PD-1 works by keeping the immune&#xD;
      system from destroying cancer cells. Stopping PD-1 from working may help the immune system to&#xD;
      fight cancer cells.&#xD;
&#xD;
      Cyclophosphamide is chemotherapy drug that is approved for the treatment of various cancers&#xD;
      alone and in combination with other drugs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study has two phases: a dose escalation phase and a dose expansion phase.&#xD;
&#xD;
      For the dose escalation part, groups of participants will receive one of two dose levels of&#xD;
      study drugs to determine the best dose level for further testing.&#xD;
&#xD;
      Once the best dose level is found, additional participant will be enrolled to the dose&#xD;
      expansion to further test the safety, tolerability, and efficacy of the study drugs at that&#xD;
      dose level in specific types of cancers. All participants will receive pembrolizumab,&#xD;
      DPX-Survivac, and low-dose cyclophosphamide.&#xD;
&#xD;
      Participants will be screened for eligibility by standard safety tests and procedures within&#xD;
      28 days of the start of the study drug. Tests and procedures done for research purposes only&#xD;
      during this time include archival tumor tissue collection, fresh research biopsy, and blood&#xD;
      sample collection for biomarker/genetic/immune research. Participants will also be asked if&#xD;
      they agree to an optional fresh research biopsy at disease progression&#xD;
&#xD;
      Eligible participants will receive the following every 21 day cycle:&#xD;
&#xD;
        -  Pembrolizumab, intravenously, at 200 mg, on Day 1 of every cycle.&#xD;
&#xD;
        -  DPX-Survivac, by injection under the skin of the upper thigh in clinic. Participants&#xD;
           will receive one priming dose of 0.25 mL of DPX-Survivac on Cycle 1 Day 1. After about 6&#xD;
           weeks, participants will receive an additional boosting dose of 0.25 or 0.5 mL&#xD;
           DPX-Survivac depending on the assigned dose level.&#xD;
&#xD;
        -  Cyclophosphamide, orally, at 50 mg, twice a day, starting about 7 days before Cycle 1&#xD;
           Day 1, then continue 7 days off, 7 days on.&#xD;
&#xD;
      While receiving the study treatment, participants will be asked to visit the study site on&#xD;
      Day 1 of Cycles 1-8 for tests and procedures. Tests and procedures done for research purposes&#xD;
      only include additional blood sample collection and a second fresh research biopsy for&#xD;
      biomarker/genetic/immune research.&#xD;
&#xD;
      Participants who benefit from the study treatment may be able to receive additional treatment&#xD;
      if they progress after stopping the study treatment.&#xD;
&#xD;
      When participants are taken off the study treatment permanently, they will be asked to return&#xD;
      to the study site for an End of Study Treatment visit about 30 days after stopping the study&#xD;
      treatment to have tests and procedures done for safety purposes.&#xD;
&#xD;
      Participants who are taken off the study treatment for any reason other than disease&#xD;
      progression will continue to have radiological assessments and blood draws every 12 weeks for&#xD;
      the first year and every 24 weeks after year 1 until they start a new anti-cancer treatment,&#xD;
      disease progression, or the study ends. Participants will continue to be followed for&#xD;
      survival and to review any new anti-cancer therapies every 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 12, 2018</start_date>
  <completion_date type="Anticipated">February 12, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 12, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>5 years</time_frame>
    <description>ORR will be used to evaluate the clinical anti-tumor activity of Pembrolizumab, DPX Survivac and oral cyclophosphamide combination.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) rate</measure>
    <time_frame>5 years</time_frame>
    <description>PFS rate from start of study treatment to time of progression or death whichever comes first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) rate</measure>
    <time_frame>5 years</time_frame>
    <description>OS rate from start of study treatment until death for every cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of side effects</measure>
    <time_frame>5 years</time_frame>
    <description>Adverse events will be analyzed as safety parameters</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Advanced Cancer</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Primary Peritoneal Carcinoma</condition>
  <condition>Fallopian Tube Cancer</condition>
  <arm_group>
    <arm_group_label>Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with epithelial ovarian, fallopian tube or primary peritoneal cancer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion - Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion - Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion - Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with recurrent advanced epithelial ovarian, fallopian tube and primary peritoneal patients with uncommon tumor histologies, including clear cell, mucinous and low grade serous or low grade endometrioid ovarian subtypes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given intravenously in clinic, at 200 mg, on Day 1 of every 21-day cycle.</description>
    <arm_group_label>Dose Escalation</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort A</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort B</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort C</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>DPX-Survivac</intervention_name>
    <description>Given by injection under the skin of the upper thigh in clinic. Participants will receive one priming dose of 0.25 mL of DPX-Survivac on Cycle 1 Day 1. After about 6 weeks, participants will receive an additional boosting dose of 0.25 or 0.5 mL DPX-Survivac.</description>
    <arm_group_label>Dose Escalation</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort A</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort B</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort C</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>Given orally, at 50 mg, twice a day, starting about 7 days before Cycle 1 Day 1, then continue 7 days off, 7 days on.</description>
    <arm_group_label>Dose Escalation</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort A</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort B</arm_group_label>
    <arm_group_label>Dose Expansion - Cohort C</arm_group_label>
    <other_name>Procytox</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically or cytologically confirmed advanced epithelial&#xD;
             ovarian, primary peritoneal or fallopian tube carcinomas.&#xD;
&#xD;
          -  Patients must have radiologically documented disease progression from their prior line&#xD;
             of therapy.&#xD;
&#xD;
          -  Patients must have measurable disease based on RECIST 1.1.&#xD;
&#xD;
          -  Have received a front line platinum-based regimen (administered via either IV or IP)&#xD;
             following primary or interval debulking surgery with documented disease recurrence.&#xD;
&#xD;
          -  Have fulfilled the following additional requirements regarding prior treatments&#xD;
             depending on the cohort that the patient is to be enrolled in.&#xD;
&#xD;
          -  Eastern Cooperative Group (ECOG) performance status &lt;=1.&#xD;
&#xD;
          -  Life expectancy greater than 16 weeks.&#xD;
&#xD;
          -  Availability of archival tumor tissue samples. Additional samples may be requested if&#xD;
             tumor tissue provided is not adequate for quality and/or quantity as assessed by the&#xD;
             laboratory.&#xD;
&#xD;
          -  Be willing to provide tumor tissue from a newly obtained core or excisional biopsy&#xD;
             prior to start treatment and on day 15 of cycle 1.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents.&#xD;
&#xD;
          -  Diagnosis of immunodeficiency or therapy with systemic steroid or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of trial treatment.&#xD;
&#xD;
          -  History of autoimmune disease, such as but not restricted to, rheumatoid arthritis,&#xD;
             inflammatory bowel disease, systemic lupus erythematous, ankylosing spondylitis,&#xD;
             scleroderma, or multiple sclerosis requiring treatment within the last two years.&#xD;
             Patients with vitiligo or diabetes are not excluded.&#xD;
&#xD;
          -  Patients with history of thyroiditis within 5 years.&#xD;
&#xD;
          -  Patients with known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
          -  Patients with known active central nervous system (CNS) metastases and/or&#xD;
             carcinomatous meningitis.&#xD;
&#xD;
          -  Hypersensitivity to Pembrolizumab, DPX-Survivac immunovaccine, Cyclophosphamide or any&#xD;
             of their excipients.&#xD;
&#xD;
          -  Patients that have received a live vaccine within 30 days of planned start of study&#xD;
             therapy.&#xD;
&#xD;
          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or DPX-Survivac vaccine.&#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>Amit Oza, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Princess Margaret Cancer Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 20, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 24, 2017</study_first_posted>
  <last_update_submitted>June 15, 2023</last_update_submitted>
  <last_update_submitted_qc>June 15, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03029403
org study id: PESCO
nct id: NCT03029403
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a phase 2 study whose purpose is to see whether the combination of of pembrolizumab,
      DPX-Survivac vaccine and low-dose cyclophosphamide has anti-tumor activity in patients with
      advanced epithelial ovarian, fallopian tube or primary peritoneal cancer.

      DPX-Survivac is an investigational vaccine. A vaccine is a substance that is often given to
      stimulate the body's immune system (the structure and processes in the body that protects
      against harmful substances) to help prevent against certain diseases. DPX-Survivac is a
      vaccine that may teach the immune system to recognize cancer cells and to kill them.

      Pembrolizumab is a drug that is approved for the treatment of a certain type of melanoma (a
      type of skin cancer) and non-small cell lung cancer. Pembrolizumab blocks the function of a
      protein called programmed cell death receptor-1 (PD-1). PD-1 works by keeping the immune
      system from destroying cancer cells. Stopping PD-1 from working may help the immune system to
      fight cancer cells.

      Cyclophosphamide is chemotherapy drug that is approved for the treatment of various cancers
      alone and in combination with other drugs.
This study has two phases: a dose escalation phase and a dose expansion phase.

      For the dose escalation part, groups of participants will receive one of two dose levels of
      study drugs to determine the best dose level for further testing.

      Once the best dose level is found, additional participant will be enrolled to the dose
      expansion to further test the safety, tolerability, and efficacy of the study drugs at that
      dose level in specific types of cancers. All participants will receive pembrolizumab,
      DPX-Survivac, and low-dose cyclophosphamide.

      Participants will be screened for eligibility by standard safety tests and procedures within
      28 days of the start of the study drug. Tests and procedures done for research purposes only
      during this time include archival tumor tissue collection, fresh research biopsy, and blood
      sample collection for biomarker/genetic/immune research. Participants will also be asked if
      they agree to an optional fresh research biopsy at disease progression

      Eligible participants will receive the following every 21 day cycle:

        -  Pembrolizumab, intravenously, at 200 mg, on Day 1 of every cycle.

        -  DPX-Survivac, by injection under the skin of the upper thigh in clinic. Participants
           will receive one priming dose of 0.25 mL of DPX-Survivac on Cycle 1 Day 1. After about 6
           weeks, participants will receive an additional boosting dose of 0.25 or 0.5 mL
           DPX-Survivac depending on the assigned dose level.

        -  Cyclophosphamide, orally, at 50 mg, twice a day, starting about 7 days before Cycle 1
           Day 1, then continue 7 days off, 7 days on.

      While receiving the study treatment, participants will be asked to visit the study site on
      Day 1 of Cycles 1-8 for tests and procedures. Tests and procedures done for research purposes
      only include additional blood sample collection and a second fresh research biopsy for
      biomarker/genetic/immune research.

      Participants who benefit from the study treatment may be able to receive additional treatment
      if they progress after stopping the study treatment.

      When participants are taken off the study treatment permanently, they will be asked to return
      to the study site for an End of Study Treatment visit about 30 days after stopping the study
      treatment to have tests and procedures done for safety purposes.

      Participants who are taken off the study treatment for any reason other than disease
      progression will continue to have radiological assessments and blood draws every 12 weeks for
      the first year and every 24 weeks after year 1 until they start a new anti-cancer treatment,
      disease progression, or the study ends. Participants will continue to be followed for
      survival and to review any new anti-cancer therapies every 12 weeks.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall response rate (ORR)
time frame: 5 years
description: ORR will be used to evaluate the clinical anti-tumor activity of Pembrolizumab, DPX Survivac and oral cyclophosphamide combination.
measure: Progression free survival (PFS) rate
time frame: 5 years
description: PFS rate from start of study treatment to time of progression or death whichever comes first
measure: Overall survival (OS) rate
time frame: 5 years
description: OS rate from start of study treatment until death for every cause
measure: Number of side effects
time frame: 5 years
description: Adverse events will be analyzed as safety parameters
arm group label: Dose Escalation
arm group type: Experimental
description: Patients with epithelial ovarian, fallopian tube or primary peritoneal cancer.
arm group label: Dose Expansion - Cohort A
arm group type: Experimental
description: Patients with platinum-sensitive epithelial ovarian, fallopian tube or primary peritoneal cancer.
arm group label: Dose Expansion - Cohort B
arm group type: Experimental
description: Patients with platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer.
arm group label: Dose Expansion - Cohort C
arm group type: Experimental
description: Patients with recurrent advanced epithelial ovarian, fallopian tube and primary peritoneal patients with uncommon tumor histologies, including clear cell, mucinous and low grade serous or low grade endometrioid ovarian subtypes.
intervention type: Drug
intervention name: Pembrolizumab
description: Given intravenously in clinic, at 200 mg, on Day 1 of every 21-day cycle.
arm group label: Dose Escalation
arm group label: Dose Expansion - Cohort A
arm group label: Dose Expansion - Cohort B
arm group label: Dose Expansion - Cohort C
other name: Keytruda
intervention type: Biological
intervention name: DPX-Survivac
description: Given by injection under the skin of the upper thigh in clinic. Participants will receive one priming dose of 0.25 mL of DPX-Survivac on Cycle 1 Day 1. After about 6 weeks, participants will receive an additional boosting dose of 0.25 or 0.5 mL DPX-Survivac.
arm group label: Dose Escalation
arm group label: Dose Expansion - Cohort A
arm group label: Dose Expansion - Cohort B
arm group label: Dose Expansion - Cohort C
intervention type: Drug
intervention name: Cyclophosphamide
description: Given orally, at 50 mg, twice a day, starting about 7 days before Cycle 1 Day 1, then continue 7 days off, 7 days on.
arm group label: Dose Escalation
arm group label: Dose Expansion - Cohort A
arm group label: Dose Expansion - Cohort B
arm group label: Dose Expansion - Cohort C
other name: Procytox
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Amit Oza, M.D.
role: Principal Investigator
affiliation: Princess Margaret Cancer Centre
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Fallopian Tube Neoplasms
mesh term: Cyclophosphamide
mesh term: Pembrolizumab
sharing ipd: No