<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/NCT02262455</url>
  </required_header>
  <id_info>
    <org_study_id>STM-434-001</org_study_id>
    <nct_id>NCT02262455</nct_id>
  </id_info>
  <brief_title>Effects of STM 434 Alone or in Combination With Liposomal Doxorubicin in Patients With Ovarian Cancer or Other Advanced Solid Tumors</brief_title>
  <official_title>An Open-Label Multiple Ascending Dose Phase 1/1B Pharmacokinetic and Pharmacodynamic Study of STM 434, an Activin Type 2B Receptor Fc Fusion, Alone and in Combination With Liposomal Doxorubicin in Patients With Ovarian Cancer or Other Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Santa Maria Biotherapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Santa Maria Biotherapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I study to test the safety, pharmacokinetics and effectiveness of STM 434&#xD;
      alone, or in combination with liposomal doxorubicin, in patients with ovarian cancer or other&#xD;
      advanced solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label (identity of assigned study drug will be known) study to evaluate the&#xD;
      safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of&#xD;
      what a drug does to the body), and anti-tumor activities of STM 434 (an inhibitor of activin&#xD;
      A) in patients with ovarian cancer and other advanced solid tumors. The study will be&#xD;
      conducted in 3 phases (Part 1, Part 2 and Part 3). In the first part of the study (Part 1),&#xD;
      which will enroll patients with multiple solid tumor types, the maximum tolerated dose (MTD)&#xD;
      of STM 434 will be determined for use in the second and third parts of the study (Parts 2 and&#xD;
      3). In the second part (Part 2), which will enroll patients with ovarian cancer, STM 434 will&#xD;
      be administered alone, and in the third part (Part 3), which will enroll patients with&#xD;
      ovarian cancer, STM 434 will be given together with a chemotherapy called liposomal&#xD;
      doxorubicin. Doses of STM 434 (starting at 0.25 mg/kg up to a maximum of 4 mg/kg) will be&#xD;
      taken on one of three dosing schedules to determine the MTD. Patients will continue taking&#xD;
      STM 434 until their tumor progresses. Serial blood samples will be collected for&#xD;
      pharmacokinetic and pharmacodynamic testing and safety will be monitored throughout the&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">January 13, 2017</completion_date>
  <primary_completion_date type="Actual">January 13, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD)</measure>
    <time_frame>MTD will be assessed for STM 434 alone in Part 1 and in combination with liposomal doxorubicin in Part 3 once the last subject in each cohort completes 28 days of treatment.</time_frame>
    <description>To define the maximum tolerated dose (MTD) of STM 434 administered alone or in combination with liposomal doxorubicin chemotherapy in patients with ovarian cancer or other advanced solid tumors.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recommended Phase 2 dose (RP2D)</measure>
    <time_frame>RP2D will be assessed in Part 1 once the last subject in each cohort completes 28 days of treatment.</time_frame>
    <description>To define the recommended Phase 2 dose (RP2D) in the event that there is no maximum tolerated dose (MTD) reached.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic response rate</measure>
    <time_frame>Efficacy parameters will be assessed at three points in the study: once Part 1 and Part 3 are fully enrolled, and during Part 2 of the study. On average the review is expected to occur once every 8 months, for up to 24 months.</time_frame>
    <description>To collect preliminary radiographic response data, including CT, MRI scans, during therapy with STM 434.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Muscle function and body composition</measure>
    <time_frame>Efficacy parameters will be assessed at three points in the study: once Part 1 and Part 3 are fully enrolled, and during Part 2 of the study. On average the review is expected to occur once every 8 months for up to 24 months.</time_frame>
    <description>To collect preliminary anti-cachexia data, including body composition and laboratory parameters, during therapy with STM 434.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Endometrial Cancer</condition>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>STM 434</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>STM 434 and Liposomal Doxorubicin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>STM 434</intervention_name>
    <description>STM 434 will be administered by IV injection. There are five planned dose levels, from 0.25mg/kg to 4mg/kg, which is dependent on the cohort (group) a participant is assigned to.</description>
    <arm_group_label>STM 434</arm_group_label>
    <arm_group_label>STM 434 and Liposomal Doxorubicin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Liposomal doxorubicin</intervention_name>
    <description>Liposomal doxorubicin (40 mg/m2) will be administered once every 28 days by IV infusion prior to STM 434 for those participants enrolled in Part 3 of the trial. Liposomal doxorubicin will be administered for a maximum of 6 cycles (each cycle being 28 days).</description>
    <arm_group_label>STM 434 and Liposomal Doxorubicin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and postmenopausal females, 18 years or older&#xD;
&#xD;
          -  Advanced solid tumors with histologic diagnosis confirming cancer&#xD;
&#xD;
          -  Patients with recurrent metastatic or locally advanced disease considered refractory&#xD;
             or intolerant to all standard treatment available for their tumor, or those tumors for&#xD;
             which no standard treatment is available&#xD;
&#xD;
          -  Subjects with serous ovarian/fallopian tube/primary peritoneal, granulosa cell tumors&#xD;
             or clear cell tumors considered platinum refractory/resistant, defined as having at&#xD;
             least one prior platinum-based chemotherapeutic regimen with a subsequent&#xD;
             platinum-free interval of &lt; 12 months, having progression during platinum-based&#xD;
             therapy, or having persistent disease after a platinum-based therapy, are eligible.&#xD;
             Intolerant subjects, defined as unable to receive further platinum due to toxicity,&#xD;
             are eligible.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of gastrointestinal bleeding within the past 6 months&#xD;
&#xD;
          -  History of epistaxis requiring medical/surgical intervention (such as nasal packing)&#xD;
             within the past 6 months&#xD;
&#xD;
          -  History of central nervous system hemorrhage&#xD;
&#xD;
          -  History of bleeding diathesis or known qualitative platelet defect (including von&#xD;
             Willebrand disease)&#xD;
&#xD;
          -  Ongoing need for therapeutic anticoagulants (full dose heparin, warfarin, factor Xa or&#xD;
             direct thrombin inhibitors; rivaroxaban, apixaban, dabigatran) chronic use of aspirin&#xD;
             or anti-platelet agents (ticlopidine or clopidogrel)&#xD;
&#xD;
          -  History of hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu syndrome)&#xD;
&#xD;
          -  Myocardial infarction, unstable angina within the past 6 months, or congestive heart&#xD;
             failure New York Heart Association Class II or greater&#xD;
&#xD;
          -  Chemotherapy, hormonal therapy or radiation therapy within the past 3 weeks,&#xD;
             antibody/biologic therapy within 5 half-lives or within the past 4 weeks (whichever is&#xD;
             longer)&#xD;
&#xD;
          -  Current bowel obstruction&#xD;
&#xD;
          -  Brain metastasis&#xD;
&#xD;
          -  Known HIV infection and/or active Hepatitis B or C infection&#xD;
&#xD;
          -  Prior treatment with any investigational product within the past 4 weeks&#xD;
&#xD;
          -  Not willing to use contraception (inclusive of abstinence)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Willis Navarro, MD</last_name>
    <role>Study Director</role>
    <affiliation>Santa Maria Biotherapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2017</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>February 10, 2017</last_update_submitted>
  <last_update_submitted_qc>February 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">February 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Serous tumor</keyword>
  <keyword>Granulosa tumor</keyword>
  <keyword>Clear Cell tumor</keyword>
  <keyword>Endometrial cancer</keyword>
  <keyword>Advanced solid tumors</keyword>
  <keyword>Adenocarcinoma</keyword>
  <keyword>Prostate cancer</keyword>
  <keyword>Head and Neck cancer</keyword>
  <keyword>Lung cancer</keyword>
  <keyword>Non-small cell lung cancer</keyword>
  <keyword>Small cell lung cancer</keyword>
  <keyword>Gastric cancer</keyword>
  <keyword>Kidney cancer</keyword>
  <keyword>Pancreatic cancer</keyword>
  <keyword>Breast cancer</keyword>
  <keyword>Colorectal cancer</keyword>
  <keyword>Bladder cancer</keyword>
  <keyword>Esophagus cancer</keyword>
  <keyword>Liver cancer</keyword>
  <keyword>Hepatobiliary cancer</keyword>
  <keyword>Skin cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Endometrial Neoplasms</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>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</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/NCT02262455
org study id: STM-434-001
nct id: NCT02262455
lead sponsor: 
has dmc: No
This is a Phase I study to test the safety, pharmacokinetics and effectiveness of STM 434
      alone, or in combination with liposomal doxorubicin, in patients with ovarian cancer or other
      advanced solid tumors.
This is an open-label (identity of assigned study drug will be known) study to evaluate the
      safety, pharmacokinetics (study of what the body does to a drug), pharmacodynamics (study of
      what a drug does to the body), and anti-tumor activities of STM 434 (an inhibitor of activin
      A) in patients with ovarian cancer and other advanced solid tumors. The study will be
      conducted in 3 phases (Part 1, Part 2 and Part 3). In the first part of the study (Part 1),
      which will enroll patients with multiple solid tumor types, the maximum tolerated dose (MTD)
      of STM 434 will be determined for use in the second and third parts of the study (Parts 2 and
      3). In the second part (Part 2), which will enroll patients with ovarian cancer, STM 434 will
      be administered alone, and in the third part (Part 3), which will enroll patients with
      ovarian cancer, STM 434 will be given together with a chemotherapy called liposomal
      doxorubicin. Doses of STM 434 (starting at 0.25 mg/kg up to a maximum of 4 mg/kg) will be
      taken on one of three dosing schedules to determine the MTD. Patients will continue taking
      STM 434 until their tumor progresses. Serial blood samples will be collected for
      pharmacokinetic and pharmacodynamic testing and safety will be monitored throughout the
      study.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD)
time frame: MTD will be assessed for STM 434 alone in Part 1 and in combination with liposomal doxorubicin in Part 3 once the last subject in each cohort completes 28 days of treatment.
description: To define the maximum tolerated dose (MTD) of STM 434 administered alone or in combination with liposomal doxorubicin chemotherapy in patients with ovarian cancer or other advanced solid tumors.
measure: Recommended Phase 2 dose (RP2D)
time frame: RP2D will be assessed in Part 1 once the last subject in each cohort completes 28 days of treatment.
description: To define the recommended Phase 2 dose (RP2D) in the event that there is no maximum tolerated dose (MTD) reached.
measure: Radiographic response rate
time frame: Efficacy parameters will be assessed at three points in the study: once Part 1 and Part 3 are fully enrolled, and during Part 2 of the study. On average the review is expected to occur once every 8 months, for up to 24 months.
description: To collect preliminary radiographic response data, including CT, MRI scans, during therapy with STM 434.
measure: Muscle function and body composition
time frame: Efficacy parameters will be assessed at three points in the study: once Part 1 and Part 3 are fully enrolled, and during Part 2 of the study. On average the review is expected to occur once every 8 months for up to 24 months.
description: To collect preliminary anti-cachexia data, including body composition and laboratory parameters, during therapy with STM 434.
arm group label: STM 434
arm group type: Experimental
arm group label: STM 434 and Liposomal Doxorubicin
arm group type: Experimental
intervention type: Drug
intervention name: STM 434
description: STM 434 will be administered by IV injection. There are five planned dose levels, from 0.25mg/kg to 4mg/kg, which is dependent on the cohort (group) a participant is assigned to.
arm group label: STM 434
arm group label: STM 434 and Liposomal Doxorubicin
intervention type: Drug
intervention name: Liposomal doxorubicin
description: Liposomal doxorubicin (40 mg/m2) will be administered once every 28 days by IV infusion prior to STM 434 for those participants enrolled in Part 3 of the trial. Liposomal doxorubicin will be administered for a maximum of 6 cycles (each cycle being 28 days).
arm group label: STM 434 and Liposomal Doxorubicin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Willis Navarro, MD
role: Study Director
affiliation: Santa Maria Biotherapeutics
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Endometrial Neoplasms
mesh term: Fallopian Tube Neoplasms
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin