<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/NCT03836157</url>
  </required_header>
  <id_info>
    <org_study_id>OUSCC-IMGN-001</org_study_id>
    <nct_id>NCT03836157</nct_id>
  </id_info>
  <brief_title>Mirvetuximab Soravtansine (IMGN853) and Bevacizumab in Patients With Endometrial Cancer</brief_title>
  <official_title>Phase II Trial of Mirvetuximab Soravtansine (IMGN853) and Bevacizumab in Patients With Endometrial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oklahoma</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ImmunoGen, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oklahoma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      IMGN853 is designed to inhibit cell division and cell growth of folate receptor 1&#xD;
      (FRα)-expressing tumor cells. The purpose of this study is to test the safety of IMGN853 and&#xD;
      bevacizumab and see what effects (good and bad) that this combination treatment has on&#xD;
      subjects with recurrent endometrial cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      SCREENING: During the screening portion of the study, the subject will need to have tumor&#xD;
      tissue tested and other exams to determine if s/he may proceed to the treatment part of the&#xD;
      study. The subject's tumor tissue will be tested from either a previous or recent surgery or&#xD;
      biopsy to see if it contains the FRα protein. If the tumor is positive and the patient meets&#xD;
      all other eligibility, then the subject may proceed to treatment.&#xD;
&#xD;
      TREATMENT: Study drugs (IMGN853 and bevacizumab) will be given by vein (IV) once each cycle&#xD;
      on day 1 of 21 day cycle.&#xD;
&#xD;
      Regular cancer care exams, tests, and procedures will occur. Additionally, an eye doctor&#xD;
      visit with complete eye examination every other treatment cycle. Subjects will also&#xD;
      self-administer eye drops as prescribed by the eye doctor.&#xD;
&#xD;
      Study participation is up to three years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was not initiated.&#xD;
  </why_stopped>
  <start_date type="Anticipated">May 31, 2019</start_date>
  <completion_date type="Anticipated">May 2022</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2021</primary_completion_date>
  <phase>Phase 2</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>Response rate of patients who remain progression free</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of patients who remain progression free</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>up to 3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Endometrial Cancer</condition>
  <condition>Endometrial Adenocarcinoma</condition>
  <condition>Endometrial Serous Adenocarcinoma</condition>
  <condition>Endometrial Clear Cell Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Mirvetuximab and Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Mirvetuximab Soravtansine 6mg/kg IV (adjusted ideal body weight), on day 1 of each 21 day cycle.&#xD;
Bevacizumab 15 mg/kg, IV, on day 1 of each 21-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mirvetuximab Soravtansine</intervention_name>
    <description>The dose will not be recalculated unless the patient has ±10% weight change.</description>
    <arm_group_label>Mirvetuximab and Bevacizumab</arm_group_label>
    <other_name>IMGN853</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Subject will receive IMGN853 first followed by bevacizumab. There is no planned delay between the IMGN853 and bevacizumab administration.</description>
    <arm_group_label>Mirvetuximab and Bevacizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histological diagnosis of endometrial carcinoma (including others per&#xD;
             protocol).&#xD;
&#xD;
          2. Expression of folate receptor alpha (FRα) on either archival tumor or new biopsy is&#xD;
             required.&#xD;
&#xD;
          3. Measurable disease&#xD;
&#xD;
          4. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has&#xD;
             relapsed or is refractory to curative therapy or established treatments.&#xD;
&#xD;
          5. At least 1 prior platinum-based chemotherapeutic regimen, but not more than 2 prior&#xD;
             chemotherapeutic regimens, for management of endometrial carcinoma. Prior treatment&#xD;
             may include chemotherapy, or chemotherapy/radiation therapy . Chemotherapy&#xD;
             administered in conjunction with primary radiation as a radio-sensitized therapy will&#xD;
             be considered a systemic chemotherapy regimen&#xD;
&#xD;
          6. Female patients 18 years or older&#xD;
&#xD;
          7. Eastern Cooperative Oncology Group performance status of 0 to 1;&#xD;
&#xD;
          8. Patient must have archival tumor tissue available from the primary or recurrent cancer&#xD;
             prior to first dose. If archival tumor sample is not available, tumor sample from new&#xD;
             biopsy is acceptable.&#xD;
&#xD;
          9. Patients must have acceptable organ and marrow function as defined per protocol&#xD;
&#xD;
         10. Time from prior therapy:&#xD;
&#xD;
               1. Systemic anti-neoplastic therapy: five half-lives or four weeks, whichever is&#xD;
                  shorter. Hormonal therapy is not considered anti-neoplastic therapy.&#xD;
&#xD;
               2. Radiotherapy: wide-field radiotherapy (e.g. &gt; 30% of marrow-bearing bones)&#xD;
                  completed at least four weeks, or focal radiation completed at least two weeks,&#xD;
                  prior to starting study treatment&#xD;
&#xD;
         11. Patients must have a life expectancy of at least 3 months&#xD;
&#xD;
         12. Patients should have no major existing co-morbidities or medical conditions that will&#xD;
             preclude therapy&#xD;
&#xD;
         13. Ability to understand and the willingness to sign a written informed consent document,&#xD;
             and to comply with the requirements of the protocol; with the understanding that&#xD;
             consent may be withdrawn by the patient at any time without prejudice to future&#xD;
             medical care.&#xD;
&#xD;
         14. Female patients of reproductive potential and their male partners must agree to&#xD;
             practice 1 highly effective method of contraception and 1 additional effective&#xD;
             (barrier) method at the same time, from the time of signing the informed consent&#xD;
             through at least twelve weeks after the last dose of IMGN853 and/ or bevacizumab.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with mirvetuximab.&#xD;
&#xD;
          2. Invasive cancer within the past 2 years. Noninvasive non-melanoma skin cancers are not&#xD;
             exclusions if they have undergone complete resection.&#xD;
&#xD;
          3. Untreated or symptomatic central nervous system (CNS) metastases. Patients with&#xD;
             asymptomatic CNS metastases are eligible provided they have been clinically stable for&#xD;
             at least 4 weeks prior to first dose of study treatment), have no evidence of new or&#xD;
             emerging CNS metastasis, and are not using steroids for at least 7 days prior to first&#xD;
             dose of study treatment.&#xD;
&#xD;
          4. Unstable angina or myocardial infarction within the previous 6 months; uncontrolled&#xD;
             hypertension (defined as systolic blood pressure &gt; 150 and/or diastolic blood pressure&#xD;
             &gt; 100 mmHg on antihypertensive medications); prior history of hypertensive crisis or&#xD;
             hypertensive encephalopathy; symptomatic congestive heart failure (NYHA Class III and&#xD;
             IV); uncontrolled cardiac arrhythmia; clinically-significant vascular disease (e.g.&#xD;
             aortic aneurysm, or dissecting aneurysm), severe aortic stenosis; clinically&#xD;
             significant peripheral vascular disease; history of any CNS cerebrovascular ischemia&#xD;
             or stroke within the last 6 months.&#xD;
&#xD;
          5. Active pulmonary disease or other coexisting medical condition that would preclude&#xD;
             full compliance with the study.&#xD;
&#xD;
          6. Receiving any other investigational agents.&#xD;
&#xD;
          7. History of prior severe infusion reaction to a monoclonal antibody. Patients with&#xD;
             known hypersensitivity of Chinese hamster ovary cell products or other recombinant&#xD;
             human antibodies.&#xD;
&#xD;
          8. Persisting ≥Grade 2 toxicity (except alopecia) from previous anti-cancer treatment.&#xD;
&#xD;
          9. Patients with &gt; Grade 1 peripheral neuropathy&#xD;
&#xD;
         10. Active or chronic corneal disorder, including but not limited to the following:&#xD;
&#xD;
               -  Sjogren's syndrome&#xD;
&#xD;
               -  Fuchs corneal dystrophy (requiring treatment)&#xD;
&#xD;
               -  History of corneal transplantation&#xD;
&#xD;
               -  Active herpetic keratitis&#xD;
&#xD;
               -  Active ocular conditions requiring on-going treatment/monitoring such as wet&#xD;
                  age-related macular degeneration requiring intravitreal injections, active&#xD;
                  diabetic retinopathy with macular edema, presence of papilledema, and monocular&#xD;
                  vision.&#xD;
&#xD;
         11. Serious concurrent illness or clinically-relevant active infection, including but not&#xD;
             limited to the following:&#xD;
&#xD;
               -  Known active hepatitis B or C&#xD;
&#xD;
               -  Known Human Immunodeficiency Virus (HIV) infection&#xD;
&#xD;
               -  Varicella-zoster virus (shingles)&#xD;
&#xD;
               -  Cytomegalovirus infection&#xD;
&#xD;
               -  Any other known concurrent infectious disease, requiring IV antibiotics within 2&#xD;
                  weeks of study enrollment&#xD;
&#xD;
         12. History of cirrhotic liver disease&#xD;
&#xD;
         13. History or evidence of thrombotic or hemorrhagic disorders within 6 months before&#xD;
             first study treatment&#xD;
&#xD;
         14. Required used of folate-containing supplements (e.g. for folate deficiency)&#xD;
&#xD;
         15. Pregnancy&#xD;
&#xD;
         16. History of bowel obstruction (including subocclusive disease) related to underlying&#xD;
             disease within 6 months of study treatment.&#xD;
&#xD;
         17. Clinically-significant proteinuria defined per protocol&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Stephenson Cancer Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>June 25, 2019</last_update_submitted>
  <last_update_submitted_qc>June 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mirvetuximab soravtansine</keyword>
  <keyword>gynecologic cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Cystadenocarcinoma, Serous</mesh_term>
    <mesh_term>Adenocarcinoma, Clear Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Mirvetuximab soravtansine</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/NCT03836157
org study id: OUSCC-IMGN-001
nct id: NCT03836157
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
IMGN853 is designed to inhibit cell division and cell growth of folate receptor 1
      (FRα)-expressing tumor cells. The purpose of this study is to test the safety of IMGN853 and
      bevacizumab and see what effects (good and bad) that this combination treatment has on
      subjects with recurrent endometrial cancer.
SCREENING: During the screening portion of the study, the subject will need to have tumor
      tissue tested and other exams to determine if s/he may proceed to the treatment part of the
      study. The subject's tumor tissue will be tested from either a previous or recent surgery or
      biopsy to see if it contains the FRα protein. If the tumor is positive and the patient meets
      all other eligibility, then the subject may proceed to treatment.

      TREATMENT: Study drugs (IMGN853 and bevacizumab) will be given by vein (IV) once each cycle
      on day 1 of 21 day cycle.

      Regular cancer care exams, tests, and procedures will occur. Additionally, an eye doctor
      visit with complete eye examination every other treatment cycle. Subjects will also
      self-administer eye drops as prescribed by the eye doctor.

      Study participation is up to three years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate of patients who remain progression free
time frame: 6 months
measure: Percentage of patients who remain progression free
time frame: 6 months
measure: Incidence of adverse events
time frame: up to 3 years
measure: Progression free survival
time frame: up to 3 years
measure: Overall survival
time frame: up to 3 years
arm group label: Mirvetuximab and Bevacizumab
arm group type: Experimental
description: Mirvetuximab Soravtansine 6mg/kg IV (adjusted ideal body weight), on day 1 of each 21 day cycle.
Bevacizumab 15 mg/kg, IV, on day 1 of each 21-day cycle.
intervention type: Drug
intervention name: Mirvetuximab Soravtansine
description: The dose will not be recalculated unless the patient has ±10% weight change.
arm group label: Mirvetuximab and Bevacizumab
other name: IMGN853
intervention type: Drug
intervention name: Bevacizumab
description: Subject will receive IMGN853 first followed by bevacizumab. There is no planned delay between the IMGN853 and bevacizumab administration.
arm group label: Mirvetuximab and Bevacizumab
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Endometrial Neoplasms
mesh term: Cystadenocarcinoma, Serous
mesh term: Adenocarcinoma, Clear Cell
mesh term: Bevacizumab
mesh term: Maytansine
mesh term: Mirvetuximab soravtansine
sharing ipd: No