<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/NCT03283943</url>
  </required_header>
  <id_info>
    <org_study_id>OZM-078</org_study_id>
    <nct_id>NCT03283943</nct_id>
  </id_info>
  <brief_title>PDL-1 Inhibition and Focal Sensitizing Radiotherapy in Recurrent Ovarian/Primary Peritoneal/Fallopian Tube Cancers.</brief_title>
  <official_title>Phase I (Safety Assessment) of Durvalumab (MEDI4736) With Focal Sensitizing Radiotherapy in Platinum Resistant Ovarian, Primary Peritoneal or Fallopian Tube Epithelial Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>British Columbia Cancer Agency</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ozmosis Research Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>British Columbia Cancer Agency</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is postulated that focal sensitizing radiotherapy may potentiate the effectiveness of&#xD;
      durvalumab. The purpose of this study is to test the safety and tolerability of 2 different&#xD;
      dose levels of focal sensitizing radiation therapy given with durvalumab.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Durvalumab is a PDL-1 inhibitor, part of class of agents (called checkpoint inhibitors)&#xD;
      designed to increase the ability of the immune system to recognize and work to eliminate&#xD;
      cancers. Checkpoint inhibitors have been studied in recurrent ovarian, primary peritoneal and&#xD;
      Fallopian cancers, and on their own show a low level of activity.&#xD;
&#xD;
      Radiation therapy is usually used in women with recurrent ovarian, primary peritoneal and&#xD;
      Fallopian cancers to palliate symptoms related to progressive disease. However, radiation is&#xD;
      know to modify the cancer immune environment and to release tumour antigens. These actions&#xD;
      may potentiate the function of immune checkpoint inhibitors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 1, 2018</start_date>
  <completion_date type="Anticipated">December 16, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 16, 2020</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>Determine the maximum tolerated dose of durvalumab combined with focal irradiation for use in recurrent ovarian cancer</measure>
    <time_frame>First 4 weeks of therapy</time_frame>
    <description>The maximum tolerated dose will be defined by dose-limiting toxicities and serious adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months</time_frame>
    <description>Objective Response rate as evaluated by RECIST (v 1.1) criteria 2) Progression free survival 3) Overall survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CA-125 response rate</measure>
    <time_frame>From date of study enrollment until confirmed CA-125 progression, through study completion, an average of 1 year</time_frame>
    <description>Using GCIG CA-125 response criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune-related response rate</measure>
    <time_frame>From date of study enrollment until confirmed immune-related disease progression, through study completion, an average of one1year</time_frame>
    <description>Using Immune-related response criteria</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Survival</measure>
    <time_frame>From date of study enrollment until death or study completion (maximum 12 months).</time_frame>
    <description>Progression free survival and overall survival of the study population</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">22</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Primary Peritoneal Carcinoma</condition>
  <condition>Fallopian Tube Cancer</condition>
  <arm_group>
    <arm_group_label>Durvalumab and focal radiotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Durvalumab 1500 mg IV every 28 days, and 2 fractions of focal sensitizing radiation with cycles 1 and 2 of treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Focal radiotherapy</intervention_name>
    <description>Focal sensitizing radiotherapy will be given at a starting dose level of 24 Gray (6 Gy X 4 fractions), and may be escalated to 32 Gy (8Gy X4 fractions).</description>
    <arm_group_label>Durvalumab and focal radiotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Durvalumab 1500 mg IV every 28 days</description>
    <arm_group_label>Durvalumab and focal radiotherapy</arm_group_label>
    <other_name>MEDI 4736</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of written informed consent prior to any study specific procedures&#xD;
&#xD;
          -  Female patients aged 19 years and older&#xD;
&#xD;
          -  Platinum-resistant (progression within 6 months of platinum based regimen) or&#xD;
             platinum-refractory ovarian/fallopian tube/peritoneal origin.&#xD;
&#xD;
          -  High grade serous, endometrioid, clear cell, mucinous, malignant mixed Mullerian&#xD;
             tumor, and low grade serous histotypes are permitted. Non-epithelial tumours will not&#xD;
             be permitted.&#xD;
&#xD;
          -  ECOG performance status 0-1.&#xD;
&#xD;
          -  No more than 2 lines of therapy in the platinum-resistant setting.&#xD;
&#xD;
          -  No bowel obstructions within the preceding 6 months.&#xD;
&#xD;
          -  Last radiation therapy treatment ≥3 months prior to enrollment.&#xD;
&#xD;
          -  Expected survival &gt;3 months.&#xD;
&#xD;
          -  All patients much have at least one site of measurable disease as defined by RECIST&#xD;
             criteria (v.1.1).&#xD;
&#xD;
          -  All patients must have disease suitable for core biopsy and agree to study related&#xD;
             biopsies. Disease suitable for biopsy can serve as radiation targets, but cannot be&#xD;
             used for response assessment.&#xD;
&#xD;
          -  All patients must have at least 2 additional sites of disease that serve are suitable&#xD;
             radiation targets (see section 6.2.1).&#xD;
&#xD;
          -  Lesions suitable for radiation targeting must meet all of the following criteria:&#xD;
&#xD;
          -  each target must be &gt; 4 cc in volume by standard imaging techniques, such as CT scan,&#xD;
             MRI, or radiograph&#xD;
&#xD;
          -  for each lesion, partial treatment of a tumour mass is permitted, but the treatment&#xD;
             volume cannot be less than the equivalent of a 2cm sphere (4cc) and the two targets&#xD;
             cannot be part of the same contiguous mass&#xD;
&#xD;
          -  must be outside of previously irradiated fields 12. Adequate organ and marrow function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who cannot meet all the radiation planning constraints will not be eligible&#xD;
             for this trial.&#xD;
&#xD;
          -  Participation in another clinical study with an investigational agent during the last&#xD;
             4 weeks.&#xD;
&#xD;
          -  Concurrent enrolment in another clinical study, the only exception being observational&#xD;
             (non-interventional) clinical studies.&#xD;
&#xD;
          -  History of pneumonitis requiring treatment with steroids, or has a history of&#xD;
             interstitial lung disease.&#xD;
&#xD;
          -  Patients who have contraindications to receiving radiation therapy, such as:&#xD;
             Rheumatoid Arthritis, connective tissue disorders, Lupus, scleroderma, CREST syndrome,&#xD;
             Crohn's syndrome, Ulcerative colitis, or other conditions identified by the Radiation&#xD;
             Oncologist as unsuitable for radiation therapy.&#xD;
&#xD;
          -  Current or prior use of immunosuppressive medication within 28 days before the first&#xD;
             dose of the study drug, with the exception of intra-nasal and inhaled corticosteroids&#xD;
             or systemic corticosteroids at physiologic doses, which must not exceed 10 mg/day of&#xD;
             prednisone, or an equivalent corticosteroid.&#xD;
&#xD;
          -  Prior exposure to an anti-PD-1 or anti-PD-L1 antibody.(including durvalumab&#xD;
&#xD;
          -  History of acute diverticulitis, intra-abdominal abscess, or GI obstruction.&#xD;
&#xD;
          -  Previous severe hypersensitivity reaction to another monoclonal antibody (mAb).&#xD;
&#xD;
          -  Active autoimmune disease or a documented history of autoimmune disease or syndrome&#xD;
             that requires systemic steroids or immunosuppressive agents. Patients with Vitiligo,&#xD;
             Grave's disease or psoriasis not requiring systemic treatment (within the past 2&#xD;
             years) or those with resolved childhood asthma/atopy are not excluded.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including: infection requiring therapy, symptomatic&#xD;
             congestive heart failure, uncontrolled hypertension (systolic blood pressure &gt; 150 and&#xD;
             diastolic blood pressure &gt;100), unstable angina pectoris, cardiac arrhythmia, active&#xD;
             peptic ulcer disease or gastritis, active bleeding diatheses.&#xD;
&#xD;
          -  Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from using&#xD;
             Frediricia'sCorrection.&#xD;
&#xD;
          -  Positive for Human Immunodeficiency Virus (HIV), Hepatitis B (Hepatitis B Surface&#xD;
             Antigen [HBsAg] reactive), or Hepatitis C virus (Hepatitis C Virus Ribonucleic Acid&#xD;
             [HCV RNA] (qualitative) is detected).&#xD;
&#xD;
          -  Previous clinical diagnosis of active tuberculosis.&#xD;
&#xD;
          -  Receipt of a live attenuated vaccination within 30 days of study entry or within 30&#xD;
             days or receiving the study drug.&#xD;
&#xD;
          -  History of another malignancy, with the exception of:&#xD;
&#xD;
          -  Malignancy treated with curative intent without evidence of recurrence for ≥ 5 years&#xD;
&#xD;
          -  Adequately treated non -melanoma skin cancer or lentigo maligna without evidence of&#xD;
             disease&#xD;
&#xD;
          -  Adequately treated carcinoma in situ without evidence of disease e.g. cervical&#xD;
             carcinoma in situ&#xD;
&#xD;
          -  Female patients who are pregnant, breast-feeding or of childbearing potential who are&#xD;
             not employing an effective method of birth control (see Table 3).&#xD;
&#xD;
          -  Any condition that, in the opinion of the investigator, would interfere with&#xD;
             evaluation of the study drug or interpretation of patient safety or study.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Anna Tinker, MD</last_name>
    <phone>604-877-6000</phone>
    <email>atinker@bccancer.bc.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>BC Cancer Agency</name>
      <address>
        <city>Vancouver</city>
        <state>British Columbia</state>
        <zip>V5Z 4E6</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Tinker, MD</last_name>
      <phone>6048776000</phone>
      <email>atinker@bccancer.bc.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>June 30, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>July 10, 2018</last_update_submitted>
  <last_update_submitted_qc>July 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>British Columbia Cancer Agency</investigator_affiliation>
    <investigator_full_name>Anna Tinker</investigator_full_name>
    <investigator_title>Medical Oncologist</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/43/NCT03283943/Prot_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03283943
org study id: OZM-078
nct id: NCT03283943
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
It is postulated that focal sensitizing radiotherapy may potentiate the effectiveness of
      durvalumab. The purpose of this study is to test the safety and tolerability of 2 different
      dose levels of focal sensitizing radiation therapy given with durvalumab.
Durvalumab is a PDL-1 inhibitor, part of class of agents (called checkpoint inhibitors)
      designed to increase the ability of the immune system to recognize and work to eliminate
      cancers. Checkpoint inhibitors have been studied in recurrent ovarian, primary peritoneal and
      Fallopian cancers, and on their own show a low level of activity.

      Radiation therapy is usually used in women with recurrent ovarian, primary peritoneal and
      Fallopian cancers to palliate symptoms related to progressive disease. However, radiation is
      know to modify the cancer immune environment and to release tumour antigens. These actions
      may potentiate the function of immune checkpoint inhibitors.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determine the maximum tolerated dose of durvalumab combined with focal irradiation for use in recurrent ovarian cancer
time frame: First 4 weeks of therapy
description: The maximum tolerated dose will be defined by dose-limiting toxicities and serious adverse events.
measure: Objective response rate
time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
description: Objective Response rate as evaluated by RECIST (v 1.1) criteria 2) Progression free survival 3) Overall survival
measure: CA-125 response rate
time frame: From date of study enrollment until confirmed CA-125 progression, through study completion, an average of 1 year
description: Using GCIG CA-125 response criteria
measure: Immune-related response rate
time frame: From date of study enrollment until confirmed immune-related disease progression, through study completion, an average of one1year
description: Using Immune-related response criteria
measure: Survival
time frame: From date of study enrollment until death or study completion (maximum 12 months).
description: Progression free survival and overall survival of the study population
arm group label: Durvalumab and focal radiotherapy
arm group type: Experimental
description: Durvalumab 1500 mg IV every 28 days, and 2 fractions of focal sensitizing radiation with cycles 1 and 2 of treatment.
intervention type: Radiation
intervention name: Focal radiotherapy
description: Focal sensitizing radiotherapy will be given at a starting dose level of 24 Gray (6 Gy X 4 fractions), and may be escalated to 32 Gy (8Gy X4 fractions).
arm group label: Durvalumab and focal radiotherapy
intervention type: Drug
intervention name: Durvalumab
description: Durvalumab 1500 mg IV every 28 days
arm group label: Durvalumab and focal radiotherapy
other name: MEDI 4736
criteria: 
gender: Female
gender based: Yes
minimum age: 19 Years
maximum age: 99 Years
healthy volunteers: No
last name: Anna Tinker, MD
phone: 604-877-6000
email: atinker@bccancer.bc.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: British Columbia Cancer Agency
investigator full name: Anna Tinker
investigator title: Medical Oncologist
mesh term: Carcinoma
mesh term: Fallopian Tube Neoplasms
mesh term: Durvalumab
sharing ipd: No
provided document: 