<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/NCT02996825</url>
  </required_header>
  <id_info>
    <org_study_id>16294</org_study_id>
    <secondary_id>NCI-2016-01913</secondary_id>
    <secondary_id>16294</secondary_id>
    <nct_id>NCT02996825</nct_id>
  </id_info>
  <brief_title>Mirvetuximab Soravtansine and Gemcitabine Hydrochloride in Treating Patients With FRalpha-Positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial, or Triple Negative Breast Cancer</brief_title>
  <official_title>A Phase I Dose-Escalation Safety and Tolerability Study of MirvetuximabSoravtansine (IMGN853) and Gemcitabine in Patients With FRa-positive Recurrent Ovarian, Primary Peritoneal, Fallopian Tube, Endometrial Cancer, or Triple Negative Breast Cancer (TNBC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>City of Hope Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>City of Hope Medical Center</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>
      This phase I trial studies the side effects and best dose of mirvetuximab soravtansine and&#xD;
      gemcitabine hydrochloride in treating patients with folate receptor (FR) alpha-positive&#xD;
      ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer&#xD;
      that has come back. Mirvetuximab soravtansine is a monoclonal antibody, called mirvetuximab,&#xD;
      linked to a chemotherapy drug called DM4. Mirvetuximab attaches to FOLR1 positive cancer&#xD;
      cells in a targeted way and delivers DM4 to kill them. Drugs used in the chemotherapy, such&#xD;
      as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells,&#xD;
      either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
      spreading. Giving mirvetuximab soravtansine and gemcitabine may work better in treating&#xD;
      patients with FRalpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or&#xD;
      triple negative breast cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of&#xD;
      gemcitabine hydrochloride (gemcitabine) when given in combination with mirvetuximab&#xD;
      soravtansine (IMGN853) to patients with FRalpha-positive recurrent ovarian, primary&#xD;
      peritoneal, fallopian tube, endometrial cancer, or triple negative breast cancer (TNBC).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To explore the toxicity, response rate (RR) and progression free survival (PFS) in three&#xD;
      expanded cohorts of heavily pre-treated FRalpha-positive a) TNBC patients; b) endometrial&#xD;
      cancer patients; and c) ovarian, primary peritoneal, or fallopian tube cancer patients, all&#xD;
      treated at the initial recommended phase II dose.&#xD;
&#xD;
      II. To provide additional safety data from the expanded cohorts to help inform on the RP2D&#xD;
      for each cohort.&#xD;
&#xD;
      III. To evaluate the relationship between intratumoral levels of DM4, tumoral expression of&#xD;
      FRalpha, and plasma concentration of DM4 at 48 and 72 hours following the first dose.&#xD;
&#xD;
      IV. To determine the pharmacokinetics (PK) of DM4 and gemcitabine when given in combination.&#xD;
&#xD;
      EXPLORATORY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the role of archival FRalpha expression as a substitute for the 48-72 hour (H)&#xD;
      expression in determining intratumoral concentration of DM4.&#xD;
&#xD;
      OUTLINE: This is a dose escalation study.&#xD;
&#xD;
      Patients receive mirvetuximab soravtansine intravenously (IV) on day 1 and gemcitabine&#xD;
      hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 3 weeks in the absence&#xD;
      of disease progression or unexpected toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are follow up at 30 days and then every 12&#xD;
      weeks thereafter.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 22, 2017</start_date>
  <completion_date type="Anticipated">November 22, 2023</completion_date>
  <primary_completion_date type="Anticipated">November 22, 2023</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>Recommended phase II dose assessed by Common Terminology Criteria for Adverse Events version 4</measure>
    <time_frame>Up to 3 weeks</time_frame>
    <description>Tables will be created to summarize toxicities by dose level, cycles delivered, and total dose delivered, and side effects by dose and by cycle.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events and clinically significant &gt;= grade 3 changes assessed by Common Terminology Criteria for Adverse Events version 4.0</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will assess the type, severity and attribution, time to onset, and duration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>Up to 2 years</time_frame>
    <description>Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Time from study entry to disease progression, assessed up to 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of biological correlatives assessed by biopsy</measure>
    <time_frame>Up to 2 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>FRalpha expression</measure>
    <time_frame>Day 1</time_frame>
    <description>FRalpha expression at baseline (in archival tissue) and in a single research biopsy (Cohort C only) at 48-72H will be correlated to intratumoral and circulating levels of DM4. Will develop a model incorporating both blood levels and FRalpha expression as predictors of DM4 intratumoral drug concentration.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Recurrent Breast Carcinoma</condition>
  <condition>Recurrent Fallopian Tube Carcinoma</condition>
  <condition>Recurrent Ovarian Carcinoma</condition>
  <condition>Recurrent Primary Peritoneal Carcinoma</condition>
  <condition>Recurrent Uterine Corpus Carcinoma</condition>
  <condition>Triple-Negative Breast Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (IMGN853, gemcitabine hydrochloride)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive mirvetuximab soravtansine IV on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 3 weeks in the absence of disease progression or unexpected toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (IMGN853, gemcitabine hydrochloride)</arm_group_label>
    <other_name>dFdC</other_name>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gemcitabine Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (IMGN853, gemcitabine hydrochloride)</arm_group_label>
    <other_name>dFdCyd</other_name>
    <other_name>Difluorodeoxycytidine Hydrochloride</other_name>
    <other_name>FF 10832</other_name>
    <other_name>FF-10832</other_name>
    <other_name>FF10832</other_name>
    <other_name>Gemcitabine HCI</other_name>
    <other_name>Gemzar</other_name>
    <other_name>LY-188011</other_name>
    <other_name>LY188011</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (IMGN853, gemcitabine hydrochloride)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mirvetuximab Soravtansine</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (IMGN853, gemcitabine hydrochloride)</arm_group_label>
    <other_name>IMGN853</other_name>
    <other_name>M9346A-sulfo-SPDB-DM4</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (IMGN853, gemcitabine hydrochloride)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients must have one of the following pathologically documented recurrent tumor&#xD;
             types with FRalpha positivity by the Ventana immunohistochemistry (IHC):&#xD;
&#xD;
               -  Ovarian, primary peritoneal, fallopian tube (with exclusion of low grade, clear&#xD;
                  cell or sarcomatoid histologies for ovarian cancer) &gt;= 50% of tumor staining &gt;=&#xD;
                  2+ intensity&#xD;
&#xD;
               -  Endometrial &gt;= 50% of tumor staining &gt;= 2+ intensity&#xD;
&#xD;
               -  TNBC confirmed by medical history of HER2-negative (confirmed by IHC 0, 1+&#xD;
                  regardless of fluorescence in situ hybridization [FISH] ratio; IHC 2+ with FISH&#xD;
                  ratio &lt; 2.0 or HER2 gene copy &lt; 6.0; FISH ratio of 0, indicating gene deletion;&#xD;
                  when positive and negative in situ hybridization controls are present); estrogen&#xD;
                  receptor (ER) negative (confirmed as ER expression =&lt; 1% positive tumor nuclei);&#xD;
                  progesterone receptor (PR) negative (confirmed as PR expression =&lt; 1% positive&#xD;
                  tumor nuclei): &gt;= 25% of tumor staining &gt;= 1+ intensity&#xD;
&#xD;
          -  Patients must have measurable disease, defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension (longest diameter to be recorded for&#xD;
             non-nodal lesions &gt;= 10 mm and short axis for nodal lesions &gt;= 15 mm); patients with&#xD;
             recurrent ovarian, primary peritoneal, fallopian tube cancer may have biochemical&#xD;
             relapse only, with baseline values of CA-125 at least 2 X upper limit of normal (ULN)&#xD;
&#xD;
          -  Treatment with targeted agents, immunotherapy, or hormones is allowed; patients are&#xD;
             only eligible if they have received and failed, or have been intolerant to standard&#xD;
             treatments known to confer clinical benefit&#xD;
&#xD;
          -  Life expectancy of greater than 3 months&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1.5 x 10^9/L, determined within 14 days of registration&#xD;
&#xD;
          -  Platelets &gt;= 100 x 10^9/L, determined within 14 days of registration&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN), determined within 14 days of&#xD;
             registration&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 X institutional upper limit of normal, determined within 14 days of&#xD;
             registration&#xD;
&#xD;
          -  Alkaline phosphatase =&lt; 2.5 X institutional upper limit of normal, determined within&#xD;
             14 days of registration&#xD;
&#xD;
          -  Creatinine clearance &gt;= 50 mL/min/1.73 m^2 for patients with creatinine levels above&#xD;
             institutional normal, determined within 14 days of registration&#xD;
&#xD;
          -  Women of childbearing potential must have a negative pregnancy test at screening and&#xD;
             must agree to use adequate contraception prior to study entry, for the duration of&#xD;
             study participation, and for 3 months after the last dose of IMGN853 and gemcitabine&#xD;
&#xD;
          -  Patients must consent to analysis on archival tissue&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
          -  Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy&#xD;
             to grade 1 or less (except alopecia)&#xD;
&#xD;
          -  Cohort A: Patients with TNBC must have received no more than 4 lines of systemic&#xD;
             cytotoxic chemotherapy; patients must have received and failed, or have been&#xD;
             intolerant to anthracycline, taxanes, capecitabine, eribulin or other agents known to&#xD;
             confer clinical benefit; patients are not required to fail all these agents if, in the&#xD;
             investigator's opinion, patients would benefit from treatment on current protocol&#xD;
&#xD;
          -  Cohort B: Patients with recurrent endometrial cancer may have received up to 2 lines&#xD;
             of cytotoxic chemotherapy (adjuvant and one line for recurrent disease, or 2 lines of&#xD;
             chemotherapy for recurrent uterine cancer in patients who did not receive adjuvant&#xD;
             chemotherapy); patients must have received and failed, or have been intolerant to&#xD;
             platinum agents, taxanes, liposomal doxorubicin or other agents known to confer&#xD;
             clinical benefit; patients are not required to fail all these agents if, in the&#xD;
             investigator's opinion, patients would benefit from treatment on current protocol&#xD;
&#xD;
          -  Cohort C: Eligible patients must have received no more than 4 lines of systemic&#xD;
             cytotoxic chemotherapy and must have disease resistant to platinum therapy (disease&#xD;
             that progressed during or within six months of completing subsequent platinum&#xD;
             therapy); primary platinum refractory patients are eligible providing they meet other&#xD;
             eligibility criteria; in addition to platinum agents, patients must have received and&#xD;
             failed, or have been intolerant to taxanes, liposomal doxorubicin or other agents&#xD;
             known to confer clinical benefit; patients are not required to fail all these agents&#xD;
             if, in the investigator's opinion, patients would benefit from treatment on current&#xD;
             protocol&#xD;
&#xD;
          -  Cohort C: Patients in this cohort only will require a single tumor biopsy 48-72H after&#xD;
             the first administration of IMGN853 and gemcitabine on day 1, cycle 1 of treatment,&#xD;
             providing it is safe/feasible and confers non-significant risk to patient&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with gemcitabine&#xD;
&#xD;
          -  Prior treatment with FR-targeting investigational agents is not allowed&#xD;
&#xD;
          -  Patients who have had chemotherapy (including investigational cytotoxic chemotherapy),&#xD;
             biologic agents (e.g., cytokines or antibodies) within 3 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) before the first dose of study treatment&#xD;
&#xD;
          -  Patients who have received radiation within 14 days before the first dose of study&#xD;
             treatment&#xD;
&#xD;
          -  Any other prior malignancy from which the patient has been disease free for less than&#xD;
             3 years, with the exception of adequately treated and basal or squamous cell skin&#xD;
             cancer, superficial bladder cancer, carcinoma in situ of any site&#xD;
&#xD;
          -  Patients with known brain metastases&#xD;
&#xD;
          -  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 with 2&#xD;
                  weeks of study enrollment&#xD;
&#xD;
          -  Other intercurrent illness including, but not limited to symptomatic congestive heart&#xD;
             failure and/or QT interval &gt; 470 for females and &gt; 450 for males, unstable angina&#xD;
             pectoris, cardiac arrhythmia, hemorrhagic or ischemic stroke within the last 6 months&#xD;
             or psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements&#xD;
&#xD;
          -  History of interstitial pneumonitis&#xD;
&#xD;
          -  History of cirrhotic liver disease&#xD;
&#xD;
          -  Presence of &gt; grade 1 peripheral neuropathy&#xD;
&#xD;
          -  Active or chronic corneal disorder, including but not limited to the following:&#xD;
             Sjogren's syndrome, Fuchs corneal dystrophy (requiring treatment), history of corneal&#xD;
             transplantation, active herpetic keratitis, and also active ocular conditions&#xD;
             requiring on-going treatment/monitoring such as wet age-related macular degeneration&#xD;
             requiring intravitreal injections, active diabetic retinopathy with macular edema,&#xD;
             presence of papilledema, and acquired monocular vision&#xD;
&#xD;
          -  Major surgery within 2 months prior to enrollment or minor surgery within 7 days of&#xD;
             the first day of treatment&#xD;
&#xD;
          -  History or evidence of thrombotic or hemorrhagic disorders within 6 months before&#xD;
             first study treatment&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to gemcitabine or IMGN853&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother is treated with gemcitabine or IMGN853&#xD;
&#xD;
          -  Required used of folate-containing supplements (e.g. folate deficiency)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edward W Wang</last_name>
    <role>Principal Investigator</role>
    <affiliation>City of Hope Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Upland</name>
      <address>
        <city>Upland</city>
        <state>California</state>
        <zip>91786</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>June 14, 2023</last_update_submitted>
  <last_update_submitted_qc>June 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 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>Carcinoma</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gemcitabine</mesh_term>
    <mesh_term>Maytansine</mesh_term>
    <mesh_term>Mirvetuximab soravtansine</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/NCT02996825
org study id: 16294
secondary id: NCI-2016-01913
secondary id: 16294
nct id: NCT02996825
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of mirvetuximab soravtansine and
      gemcitabine hydrochloride in treating patients with folate receptor (FR) alpha-positive
      ovarian, primary peritoneal, fallopian tube, endometrial, or triple negative breast cancer
      that has come back. Mirvetuximab soravtansine is a monoclonal antibody, called mirvetuximab,
      linked to a chemotherapy drug called DM4. Mirvetuximab attaches to FOLR1 positive cancer
      cells in a targeted way and delivers DM4 to kill them. Drugs used in the chemotherapy, such
      as gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells,
      either by killing the cells, by stopping them from dividing, or by stopping them from
      spreading. Giving mirvetuximab soravtansine and gemcitabine may work better in treating
      patients with FRalpha-positive ovarian, primary peritoneal, fallopian tube, endometrial, or
      triple negative breast cancer.
PRIMARY OBJECTIVE:

      I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of
      gemcitabine hydrochloride (gemcitabine) when given in combination with mirvetuximab
      soravtansine (IMGN853) to patients with FRalpha-positive recurrent ovarian, primary
      peritoneal, fallopian tube, endometrial cancer, or triple negative breast cancer (TNBC).

      SECONDARY OBJECTIVES:

      I. To explore the toxicity, response rate (RR) and progression free survival (PFS) in three
      expanded cohorts of heavily pre-treated FRalpha-positive a) TNBC patients; b) endometrial
      cancer patients; and c) ovarian, primary peritoneal, or fallopian tube cancer patients, all
      treated at the initial recommended phase II dose.

      II. To provide additional safety data from the expanded cohorts to help inform on the RP2D
      for each cohort.

      III. To evaluate the relationship between intratumoral levels of DM4, tumoral expression of
      FRalpha, and plasma concentration of DM4 at 48 and 72 hours following the first dose.

      IV. To determine the pharmacokinetics (PK) of DM4 and gemcitabine when given in combination.

      EXPLORATORY OBJECTIVE:

      I. To evaluate the role of archival FRalpha expression as a substitute for the 48-72 hour (H)
      expression in determining intratumoral concentration of DM4.

      OUTLINE: This is a dose escalation study.

      Patients receive mirvetuximab soravtansine intravenously (IV) on day 1 and gemcitabine
      hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 3 weeks in the absence
      of disease progression or unexpected toxicity.

      After completion of study treatment, patients are follow up at 30 days and then every 12
      weeks thereafter.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Recommended phase II dose assessed by Common Terminology Criteria for Adverse Events version 4
time frame: Up to 3 weeks
description: Tables will be created to summarize toxicities by dose level, cycles delivered, and total dose delivered, and side effects by dose and by cycle.
measure: Incidence of treatment-emergent adverse events and clinically significant >= grade 3 changes assessed by Common Terminology Criteria for Adverse Events version 4.0
time frame: Up to 2 years
description: Will assess the type, severity and attribution, time to onset, and duration.
measure: Response
time frame: Up to 2 years
description: Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1.
measure: Progression free survival
time frame: Time from study entry to disease progression, assessed up to 2 years
measure: Assessment of biological correlatives assessed by biopsy
time frame: Up to 2 years
measure: FRalpha expression
time frame: Day 1
description: FRalpha expression at baseline (in archival tissue) and in a single research biopsy (Cohort C only) at 48-72H will be correlated to intratumoral and circulating levels of DM4. Will develop a model incorporating both blood levels and FRalpha expression as predictors of DM4 intratumoral drug concentration.
arm group label: Treatment (IMGN853, gemcitabine hydrochloride)
arm group type: Experimental
description: Patients receive mirvetuximab soravtansine IV on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Cycles repeat every 3 weeks in the absence of disease progression or unexpected toxicity.
intervention type: Drug
intervention name: Gemcitabine
description: Given IV
arm group label: Treatment (IMGN853, gemcitabine hydrochloride)
other name: dFdC
other name: dFdCyd
other name: Difluorodeoxycytidine
intervention type: Drug
intervention name: Gemcitabine Hydrochloride
description: Given IV
arm group label: Treatment (IMGN853, gemcitabine hydrochloride)
other name: dFdCyd
other name: Difluorodeoxycytidine Hydrochloride
other name: FF 10832
other name: FF-10832
other name: FF10832
other name: Gemcitabine HCI
other name: Gemzar
other name: LY-188011
other name: LY188011
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (IMGN853, gemcitabine hydrochloride)
intervention type: Biological
intervention name: Mirvetuximab Soravtansine
description: Given IV
arm group label: Treatment (IMGN853, gemcitabine hydrochloride)
other name: IMGN853
other name: M9346A-sulfo-SPDB-DM4
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (IMGN853, gemcitabine hydrochloride)
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Edward W Wang
role: Principal Investigator
affiliation: City of Hope Medical Center
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Triple Negative Breast Neoplasms
mesh term: Breast Neoplasms
mesh term: Recurrence
mesh term: Gemcitabine
mesh term: Maytansine
mesh term: Mirvetuximab soravtansine