<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/NCT01720173</url>
  </required_header>
  <id_info>
    <org_study_id>GOG-0170R</org_study_id>
    <secondary_id>NCI-2012-01936</secondary_id>
    <secondary_id>NSC #757172</secondary_id>
    <secondary_id>CDR0000742512</secondary_id>
    <secondary_id>GOG-0170R</secondary_id>
    <secondary_id>GOG-0170R</secondary_id>
    <secondary_id>U10CA180868</secondary_id>
    <secondary_id>U10CA027469</secondary_id>
    <nct_id>NCT01720173</nct_id>
  </id_info>
  <brief_title>Dalantercept in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer</brief_title>
  <official_title>A Phase II Evaluation of Dalantercept (NSC #757172), a Novel Soluble Recombinant Activin Receptor-Like Kinase 1 (ALK-1) Inhibitor Receptor-Fusion Protein, in the Treatment of Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gynecologic Oncology Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>GOG Foundation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies the side effects and how well dalantercept works in treating&#xD;
      patients with ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer that&#xD;
      has returned. Dalantercept may stop the growth of tumor cells by blocking some of the enzymes&#xD;
      needed for cell growth. Dalantercept may also stop the growth of tumor cells by blocking&#xD;
      blood flow to the tumor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To estimate the proportion of patients who survive progression-free for at least 6 months&#xD;
      and the proportion of patients who have objective tumor response (complete or partial) in&#xD;
      patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary&#xD;
      peritoneal carcinoma, treated with dalantercept.&#xD;
&#xD;
      II. To determine the frequency and severity of adverse events associated with treatment with&#xD;
      dalantercept as assessed by the Active Version of the National Cancer Institute (NCI) Common&#xD;
      Terminology Criteria for Adverse Events (CTCAE).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the duration of progression-free survival (PFS) and overall survival (OS).&#xD;
&#xD;
      TERTIARY OBJECTIVES:&#xD;
&#xD;
      I. To measure the expression of vascular endothelial growth factor (VEGF), fibroblast growth&#xD;
      factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-B),&#xD;
      activin receptor-like kinase 1 (ALK1), cluster of differentiation 105 (CD105), and other&#xD;
      markers via immunohistochemistry (IHC) and determine if there is correlation between&#xD;
      expression and clinical response to treatment.&#xD;
&#xD;
      II. To determine the correlation between ALK1 gene expression, other markers, and clinical&#xD;
      response to treatment.&#xD;
&#xD;
      III. To determine the correlation between concentration of VEGF, bone morphogenetic protein&#xD;
      (BMP)9, BMP10, and ALK1 in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay&#xD;
      (ELISA), and clinical response to treatment.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive dalantercept subcutaneously (SC) on day 1. Courses repeat every 3 weeks in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months for 2 years and&#xD;
      then every 6 months for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2012</start_date>
  <completion_date type="Actual">February 19, 2019</completion_date>
  <primary_completion_date type="Actual">October 31, 2015</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>Progression-free for at Least 6 Months Without Non-protocol Therapy From Study Entry</measure>
    <time_frame>Every other cycle for first 6 months</time_frame>
    <description>Percentage of participants who survive progression-free for at least 6 months without non-protocol therapy after study entry. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 4.0</measure>
    <time_frame>Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up</time_frame>
    <description>Number of participants with a maximum grade of 3 or higher during the treatment period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Tumor Response</measure>
    <time_frame>Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease, up to 5 years.</time_frame>
    <description>Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.</time_frame>
    <description>Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease, up to 5 years.</time_frame>
    <description>Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Gene Expression Levels of ALK1 and Other Markers</measure>
    <time_frame>Baseline</time_frame>
    <description>Associated with measures of clinical response to treatment, including PFS and OS.</description>
  </other_outcome>
  <other_outcome>
    <measure>IHC Expression Levels of VEGF, FGF, TGFB, ALK1, CD105 and Other Markers</measure>
    <time_frame>Baseline</time_frame>
    <description>Associated with measures of clinical response to treatment, including PFS and OS.</description>
  </other_outcome>
  <other_outcome>
    <measure>Pre-treatment Plasma Concentration Levels of VEGF, BMP9, BMP10, and ALK1</measure>
    <time_frame>Baseline</time_frame>
    <description>Associated with measures of clinical response to treatment, including PFS and OS.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Recurrent Fallopian Tube Carcinoma</condition>
  <condition>Recurrent Ovarian Carcinoma</condition>
  <condition>Recurrent Primary Peritoneal Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (dalantercept)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive dalantercept SC on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Dalantercept</intervention_name>
    <description>Given SC</description>
    <arm_group_label>Treatment (dalantercept)</arm_group_label>
    <other_name>ACE-041</other_name>
    <other_name>Activin Receptor-like Kinase 1 Inhibitor ACE-041</other_name>
    <other_name>ALK1-Fc Fusion Protein ACE-041</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (dalantercept)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or&#xD;
             primary peritoneal carcinoma; histologic documentation of the original primary tumor&#xD;
             is required via the pathology report&#xD;
&#xD;
          -  All patients must have measurable disease as defined by Response Evaluation Criteria&#xD;
             in Solid Tumors (RECIST) 1.1; measurable disease is defined as at least one lesion&#xD;
             that can be accurately measured in at least one dimension (longest diameter to be&#xD;
             recorded); each lesion must be &gt;= 10 mm when measured by computed tomography (CT),&#xD;
             magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or &gt;= 20 mm&#xD;
             when measured by chest x-ray; lymph nodes must be &gt;= 15 mm in short axis when measured&#xD;
             by CT or MRI&#xD;
&#xD;
          -  Patient must have at least one &quot;target lesion&quot; to be used to assess response on this&#xD;
             protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be&#xD;
             designated as &quot;non-target&quot; lesions unless progression is documented or a biopsy is&#xD;
             obtained to confirm persistence at least 90 days following completion of radiation&#xD;
             therapy&#xD;
&#xD;
          -  Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)&#xD;
             protocol, if one exists; in general, this would refer to any active GOG phase III&#xD;
             protocol or Rare Tumor protocol for the same patient population&#xD;
&#xD;
          -  Patients who have received one prior regimen must have a GOG performance status of 0,&#xD;
             1, or 2; patients who have received two prior regimens must have a GOG performance&#xD;
             status of 0 or 1&#xD;
&#xD;
          -  Recovery from effects of recent surgery, radiotherapy, or chemotherapy:&#xD;
&#xD;
               -  Patients should be free of active infection requiring antibiotics (with the&#xD;
                  exception of uncomplicated urinary tract infection [UTI])&#xD;
&#xD;
               -  Any hormonal therapy directed at the malignant tumor must be discontinued at&#xD;
                  least one week prior to registration; continuation of hormone replacement therapy&#xD;
                  is permitted&#xD;
&#xD;
               -  Any other prior therapy directed at the malignant tumor, including immunologic&#xD;
                  agents, must be discontinued at least three weeks prior to registration; therapy&#xD;
                  with nitrosoureas or mitomycin must be discontinued at least six weeks prior to&#xD;
                  registration&#xD;
&#xD;
               -  Any prior radiation therapy must be discontinued at least four weeks prior to&#xD;
                  registration&#xD;
&#xD;
               -  At least 4 weeks must have elapsed since the patient underwent any major surgery&#xD;
                  (e.g., major: laparotomy, laparoscopy); there is no delay in treatment for minor&#xD;
                  procedures (e.g., central venous access catheter placement)&#xD;
&#xD;
          -  Prior therapy:&#xD;
&#xD;
               -  Patients must have had one prior platinum-based chemotherapeutic regimen for&#xD;
                  management of primary disease containing carboplatin, cisplatin, or another&#xD;
                  organoplatinum compound; this initial treatment may have included intraperitoneal&#xD;
                  therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g.,&#xD;
                  bevacizumab) or extended therapy administered after surgical or non-surgical&#xD;
                  assessment&#xD;
&#xD;
               -  Patients are allowed to receive, but are not required to receive, one additional&#xD;
                  cytotoxic regimen for management of recurrent or persistent disease&#xD;
&#xD;
               -  Patients who have received only one prior cytotoxic regimen (platinum-based&#xD;
                  regimen for management of primary disease), must have a platinum-free interval of&#xD;
                  less than 12 months, or have progressed during platinum-based therapy, or have&#xD;
                  persistent disease after a platinum-based therapy&#xD;
&#xD;
               -  Patients are allowed to receive, but are not required to receive,&#xD;
                  biologic/targeted (non-cytotoxic) therapy as part of their primary treatment&#xD;
                  regimen&#xD;
&#xD;
               -  Patients must have NOT received any biologic/targeted (non-cytotoxic) therapy&#xD;
                  targeting the VEGF pathway for management of recurrent or persistent disease&#xD;
&#xD;
               -  For the purposes of this study, poly (ADP-ribose) polymerase (PARP) inhibitors&#xD;
                  will be considered ?cytotoxic?; patients are allowed to receive, but are not&#xD;
                  required to receive, PARP inhibitors for management of primary or&#xD;
                  recurrent/persistent disease (either alone or in combination with cytotoxic&#xD;
                  chemotherapy); PARP inhibitors will NOT count as a prior regimen when given alone&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl&#xD;
&#xD;
          -  Platelets greater than or equal to100,000/mcl&#xD;
&#xD;
          -  Hemoglobin greater than or equal to 9 g/dl&#xD;
&#xD;
          -  Creatinine less than or equal to 1.5 x institutional upper limit normal (ULN)&#xD;
&#xD;
          -  Sodium greater than or equal to 130 mEq/L (CTCAE version 4 [v. 4], grade 0 or 1)&#xD;
&#xD;
          -  Urine protein should be screened by urinalysis; if protein is 2+ or higher, 24-hour&#xD;
             urine protein should be obtained and the level should be &lt; 1000 mg (&lt; 1.0 g/24 hrs)&#xD;
             for patient enrollment&#xD;
&#xD;
          -  Bilirubin less than or equal to 1.5 x ULN&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal&#xD;
             to 3 x ULN&#xD;
&#xD;
          -  Alkaline phosphatase less than or equal to 3 x ULN&#xD;
&#xD;
          -  Albumin greater than or equal to 3 (CTCAE v. 4, grade 0 or 1)&#xD;
&#xD;
          -  Prothrombin time (PT) such that international normalized ratio (INR) is less than or&#xD;
             equal to 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a&#xD;
             stable dose of therapeutic warfarin) and partial thromboplastin time (PTT) less than&#xD;
             or equal to 1.5 x ULN&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) greater than 50% (measured by echocardiogram&#xD;
             or MUGA [multi-gated acquisition] scan)&#xD;
&#xD;
          -  Patients must have signed an approved informed consent and authorization permitting&#xD;
             release of personal health information&#xD;
&#xD;
          -  Patients must meet pre-entry requirements&#xD;
&#xD;
          -  Patients of childbearing potential must have a negative pregnancy test prior to the&#xD;
             study entry and be practicing an effective form of contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had previous treatment with dalantercept or any other anti-ALK1&#xD;
             (activin receptor-like kinase 1) agent&#xD;
&#xD;
          -  Patients with a history of other invasive malignancies, with the exception of&#xD;
             non-melanoma skin cancer and other specific malignancies, are excluded if there is any&#xD;
             evidence of other malignancy being present within the last three years; patients are&#xD;
             also excluded if their previous cancer treatment contraindicates this protocol therapy&#xD;
&#xD;
          -  Patients who have received prior radiotherapy to any portion of the abdominal cavity&#xD;
             or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary&#xD;
             peritoneal cancer within the last three years are excluded; prior radiation for&#xD;
             localized cancer of the breast, head and neck, or skin is permitted, provided that it&#xD;
             was completed more than three years prior to registration, and the patient remains&#xD;
             free of recurrent or metastatic disease&#xD;
&#xD;
          -  Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER&#xD;
             THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within&#xD;
             the last three years are excluded; patients may have received prior adjuvant&#xD;
             chemotherapy for localized breast cancer, provided that it was completed more than&#xD;
             three years prior to registration, and that the patient remains free of recurrent or&#xD;
             metastatic disease&#xD;
&#xD;
          -  Patients with a past history of primary endometrial cancer are excluded unless all of&#xD;
             the following conditions are met: stage not greater than I-B; no more than superficial&#xD;
             myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated&#xD;
             subtypes, including papillary serious, clear cell or other International Federation of&#xD;
             Gynecology and Obstetrics (FIGO) grade 3 lesions&#xD;
&#xD;
          -  Patients with history or evidence upon physical exam of central nervous system (CNS)&#xD;
             disease, including primary brain tumor, seizures not controlled with standard medical&#xD;
             therapy or any brain metastases&#xD;
&#xD;
          -  Serious or non-healing wound, ulcer or bone fracture&#xD;
&#xD;
          -  History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess&#xD;
             within 6 months&#xD;
&#xD;
          -  Patients requiring parenteral hydration or parenteral/total parenteral nutrition&#xD;
&#xD;
          -  Patients with:&#xD;
&#xD;
               -  Active bleeding (e.g., active hemoptysis, defined as bright red blood of greater&#xD;
                  than or equal to 1/2 teaspoon [2.5 ml] in any 24 hour period within 2 weeks prior&#xD;
                  to registration or gastrointestinal bleeding within 3 months prior to&#xD;
                  registration)&#xD;
&#xD;
               -  Hereditary hemorrhagic telangiectasia (HHT)&#xD;
&#xD;
               -  Platelet function abnormality&#xD;
&#xD;
               -  Autoimmune or hereditary hemolysis&#xD;
&#xD;
               -  Coagulopathy&#xD;
&#xD;
               -  Tumor involving major vessels (defined as any lesion invading or abutting the&#xD;
                  wall [i.e., no fat plane evident] of major blood vessels as assessed by CT or&#xD;
                  MRI)&#xD;
&#xD;
          -  Patients receiving treatment with full dose aspirin (325mg oral daily), clopidogrel&#xD;
             (Plavix) or dabigatran (Pradaxa)&#xD;
&#xD;
          -  Patients with peripheral edema greater than or equal to grade 1, within 4 weeks of&#xD;
             registration&#xD;
&#xD;
          -  Patients with clinically significant cardiovascular disease:&#xD;
&#xD;
               -  Uncontrolled hypertension, defined as systolic &gt; 150 mm Hg or diastolic &gt; 90 mm&#xD;
                  Hg despite antihypertensive medications&#xD;
&#xD;
               -  Evidence of hypertrophic cardiomyopathy&#xD;
&#xD;
               -  New York Heart Association (NYHA) class II or greater congestive heart failure&#xD;
                  (CHF)&#xD;
&#xD;
               -  Any of the following within 6 months prior to study registration:&#xD;
&#xD;
                    -  Bypass surgery&#xD;
&#xD;
                    -  Stent placement&#xD;
&#xD;
                    -  Myocardial infarction&#xD;
&#xD;
                    -  Acute coronary syndrome/unstable angina&#xD;
&#xD;
                    -  Hospitalization for CHF&#xD;
&#xD;
               -  Serious cardiac arrhythmia requiring medication; this does not include&#xD;
                  asymptomatic, atrial fibrillation with controlled ventricular rate&#xD;
&#xD;
               -  Prolonged corrected QT (QTc) interval &gt; 450 ms&#xD;
&#xD;
               -  Prior anthracycline cumulative dose &gt; 450 mg/m^2&#xD;
&#xD;
          -  History of severe (National Cancer Institute-Common Terminology Criteria for Adverse&#xD;
             Events [NCI-CTCAE] v.4.0 &gt;= grade 3) allergic or anaphylactic reaction or&#xD;
             hypersensitivity to recombinant proteins or Tris buffered saline&#xD;
&#xD;
          -  Patients who are pregnant or nursing&#xD;
&#xD;
          -  History of syndrome of inappropriate antidiuretic hormone secretion (SIADH)&#xD;
&#xD;
          -  Patients who have undergone a therapeutic paracentesis within 4 weeks of registration&#xD;
&#xD;
          -  Known history of positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV)&#xD;
             surface antigen (HBsAg) or HBV core antibody, or human immunodeficiency virus (HIV)&#xD;
             antibody results&#xD;
&#xD;
          -  Clinically significant active pulmonary risk including pulmonary hypertension,&#xD;
             pulmonary embolism, or history of pulmonary edema&#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>Robert A Burger</last_name>
    <role>Principal Investigator</role>
    <affiliation>NRG Oncology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Poudre Valley Hospital</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80524</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Hospital of Central Connecticut</name>
      <address>
        <city>New Britain</city>
        <state>Connecticut</state>
        <zip>06050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beebe Medical Center</name>
      <address>
        <city>Lewes</city>
        <state>Delaware</state>
        <zip>19958</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care Health System-Christiana Hospital</name>
      <address>
        <city>Newark</city>
        <state>Delaware</state>
        <zip>19718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lewis Cancer and Research Pavilion at Saint Joseph's/Candler</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Decatur Memorial Hospital</name>
      <address>
        <city>Decatur</city>
        <state>Illinois</state>
        <zip>62526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa/Holden Comprehensive Cancer Center</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maine Medical Center-Bramhall Campus</name>
      <address>
        <city>Portland</city>
        <state>Maine</state>
        <zip>04102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christiana Care - Union Hospital</name>
      <address>
        <city>Elkton</city>
        <state>Maryland</state>
        <zip>21921</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMass Memorial Medical Center - Memorial Division</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Michigan Cancer Center</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <zip>49007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Mississippi Medical Center</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Methodist Hospital</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of New Mexico Cancer Center</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</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>Case Western Reserve University</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Cancer Center/Fairview Hospital</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hillcrest Hospital Cancer Center</name>
      <address>
        <city>Mayfield Heights</city>
        <state>Ohio</state>
        <zip>44124</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UH Seidman Cancer Center at Lake Health Mentor Campus</name>
      <address>
        <city>Mentor</city>
        <state>Ohio</state>
        <zip>44060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oklahoma Health Sciences Center</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jefferson Abington Hospital</name>
      <address>
        <city>Abington</city>
        <state>Pennsylvania</state>
        <zip>19001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fox Chase Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Women and Infants Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Cancer Center Oncology Clinic</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford NCI Community Oncology Research Program of the North Central Plains</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford USD Medical Center - Sioux Falls</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57117-5134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Don and Sybil Harrington Cancer Center</name>
      <address>
        <city>Amarillo</city>
        <state>Texas</state>
        <zip>79106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Gynecology Specialists</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center - Northwest</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Washington Medical Center - Montlake</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology at Saint Vincent Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301-3526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Vincent Hospital Cancer Center Green Bay</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Green Bay Oncology Limited at Saint Mary's Hospital</name>
      <address>
        <city>Green Bay</city>
        <state>Wisconsin</state>
        <zip>54303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Family Memorial Hospital</name>
      <address>
        <city>Manitowoc</city>
        <state>Wisconsin</state>
        <zip>54221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Area Medical Center</name>
      <address>
        <city>Marinette</city>
        <state>Wisconsin</state>
        <zip>54143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>October 30, 2012</study_first_submitted>
  <study_first_submitted_qc>October 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 2, 2012</study_first_posted>
  <results_first_submitted>August 3, 2017</results_first_submitted>
  <results_first_submitted_qc>November 1, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 8, 2017</results_first_posted>
  <last_update_submitted>September 28, 2021</last_update_submitted>
  <last_update_submitted_qc>September 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2021</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>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulin Fc Fragments</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was activated on 11/5/2012 and closed to accrual on 10/2/2013.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Dalantercept</title>
          <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Eligible and treated patients</population>
      <group_list>
        <group group_id="B1">
          <title>Dalantercept</title>
          <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.0" spread="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>30-39 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40-49 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50-59 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression-free for at Least 6 Months Without Non-protocol Therapy From Study Entry</title>
        <description>Percentage of participants who survive progression-free for at least 6 months without non-protocol therapy after study entry. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.</description>
        <time_frame>Every other cycle for first 6 months</time_frame>
        <population>Eligible and treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Dalantercept</title>
            <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free for at Least 6 Months Without Non-protocol Therapy From Study Entry</title>
          <description>Percentage of participants who survive progression-free for at least 6 months without non-protocol therapy after study entry. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.</description>
          <population>Eligible and treated participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20" lower_limit="11" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 4.0</title>
        <description>Number of participants with a maximum grade of 3 or higher during the treatment period.</description>
        <time_frame>Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up</time_frame>
        <population>Eligible and treated patients</population>
        <group_list>
          <group group_id="O1">
            <title>Dalantercept</title>
            <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 4.0</title>
          <description>Number of participants with a maximum grade of 3 or higher during the treatment period.</description>
          <population>Eligible and treated patients</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Neutropenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other Investigations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cardiac disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gastrointestinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>General disorders and administration site conditio</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Infections and infestations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolism and nutrition disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Musculoskeletal and connective tissue disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Renal and urinary disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Reproductive system and breast disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory, thoracic and mediastinal disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Objective Tumor Response</title>
        <description>Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.</description>
        <time_frame>Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease, up to 5 years.</time_frame>
        <population>Eligible and treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Dalantercept</title>
            <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Tumor Response</title>
          <description>Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.</description>
          <population>Eligible and treated participants</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.</description>
        <time_frame>Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.</time_frame>
        <population>Eligible and treated participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Dalantercept</title>
            <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.</description>
          <population>Eligible and treated participants.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.8" lower_limit="8.8" upper_limit="24.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.</description>
        <time_frame>Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease, up to 5 years.</time_frame>
        <population>Eligible and treated participants</population>
        <group_list>
          <group group_id="O1">
            <title>Dalantercept</title>
            <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.</description>
          <population>Eligible and treated participants</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.7" lower_limit="1.3" upper_limit="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Gene Expression Levels of ALK1 and Other Markers</title>
        <description>Associated with measures of clinical response to treatment, including PFS and OS.</description>
        <time_frame>Baseline</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>IHC Expression Levels of VEGF, FGF, TGFB, ALK1, CD105 and Other Markers</title>
        <description>Associated with measures of clinical response to treatment, including PFS and OS.</description>
        <time_frame>Baseline</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Pre-treatment Plasma Concentration Levels of VEGF, BMP9, BMP10, and ALK1</title>
        <description>Associated with measures of clinical response to treatment, including PFS and OS.</description>
        <time_frame>Baseline</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All Adverse Events (AEs) occurring during treatment and up to 30 days after stopping the study treatment are reported. The average time of study treatment was 3 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Dalantercept</title>
          <description>Dalantercept administered subcutaneously at a dose of 1.2mg/kg (maximum starting dose of 120 mg*) once every three weeks until disease progression or adverse effects prohibit further therapy. One cycle is 3 weeks.&#xD;
*Patients weighing more than 100kg will start treatment at 120mg, and if dalantercept is tolerated for 2 cycles (i.e. toxicities are tolerable, less than grade 2 and resolved), the patient can be dose escalated to dosing based on actual body weight.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colonic Obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin And Subcutaneous Tissue Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymph Node Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Heart Failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinus Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ear Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperparathyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral Dysesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Mucositis Oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lower Gastrointestinal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Disorders - Other</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oral Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal Distension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fecal Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Localized Edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Injection Site Reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Edema Trunk</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Non-Cardiac Chest Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Edema Limbs</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Edema Face</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic Reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Peripheral Nerve Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lip Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Weight Gain</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Platelet Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutrophil Count Decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>White Blood Cell Decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Aspartate Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alkaline Phosphatase Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alanine Aminotransferase Increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Activated Partial Thromboplastin Time Prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypernatremia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperkalemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain In Extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Osteoporosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chest Wall Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Peripheral Motor Neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Memory Impairment</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cognitive Disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Incontinence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary Tract Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal Hemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pelvic Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vaginal Discharge</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory, Thoracic And Mediastinal Disorders -</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sore Throat</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Sinus Disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nasal Congestion</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pleuritic Pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash Acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Periorbital Edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash Maculo-Papular</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Telangiectasia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Erythema Multiforme</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic Event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Angela Kuras on behalf of Wei Deng, PhD</name_or_title>
      <organization>NRG Oncology</organization>
      <phone>716-845-5702</phone>
      <email>kurasa@nrgoncology.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01720173
org study id: GOG-0170R
secondary id: NCI-2012-01936
secondary id: NSC #757172
secondary id: CDR0000742512
secondary id: GOG-0170R
secondary id: GOG-0170R
secondary id: U10CA180868
secondary id: U10CA027469
nct id: NCT01720173
lead sponsor: 
collaborator: 
has dmc: Yes
This phase II trial studies the side effects and how well dalantercept works in treating
      patients with ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer that
      has returned. Dalantercept may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Dalantercept may also stop the growth of tumor cells by blocking
      blood flow to the tumor.
PRIMARY OBJECTIVES:

      I. To estimate the proportion of patients who survive progression-free for at least 6 months
      and the proportion of patients who have objective tumor response (complete or partial) in
      patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary
      peritoneal carcinoma, treated with dalantercept.

      II. To determine the frequency and severity of adverse events associated with treatment with
      dalantercept as assessed by the Active Version of the National Cancer Institute (NCI) Common
      Terminology Criteria for Adverse Events (CTCAE).

      SECONDARY OBJECTIVES:

      I. To determine the duration of progression-free survival (PFS) and overall survival (OS).

      TERTIARY OBJECTIVES:

      I. To measure the expression of vascular endothelial growth factor (VEGF), fibroblast growth
      factor (FGF), platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-B),
      activin receptor-like kinase 1 (ALK1), cluster of differentiation 105 (CD105), and other
      markers via immunohistochemistry (IHC) and determine if there is correlation between
      expression and clinical response to treatment.

      II. To determine the correlation between ALK1 gene expression, other markers, and clinical
      response to treatment.

      III. To determine the correlation between concentration of VEGF, bone morphogenetic protein
      (BMP)9, BMP10, and ALK1 in pre-cycle 1 plasma using an enzyme-linked immunosorbent assay
      (ELISA), and clinical response to treatment.

      OUTLINE:

      Patients receive dalantercept subcutaneously (SC) on day 1. Courses repeat every 3 weeks in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years and
      then every 6 months for 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression-free for at Least 6 Months Without Non-protocol Therapy From Study Entry
time frame: Every other cycle for first 6 months
description: Percentage of participants who survive progression-free for at least 6 months without non-protocol therapy after study entry. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
measure: Incidence of Adverse Effects as Assessed by Common Terminology Criteria for Adverse Events Version 4.0
time frame: Assessed every cycle while on treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
description: Number of participants with a maximum grade of 3 or higher during the treatment period.
measure: Objective Tumor Response
time frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease, up to 5 years.
description: Complete and Partial Tumor Response by RECIST 1.1. RECIST 1.1 defines complete response as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm and the disappearance of all non-target lesions and normalization of tumor marker level. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate.
measure: Overall Survival
time frame: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.
description: Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
measure: Progression-free Survival
time frame: Every other cycle for first 6 months; then every 3 months thereafter until disease progression confirmed; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease, up to 5 years.
description: Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1. RECIST 1.1 defines progressive disease as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions or unequivocal progression of non-target lesions is also considered progression.
measure: Gene Expression Levels of ALK1 and Other Markers
time frame: Baseline
description: Associated with measures of clinical response to treatment, including PFS and OS.
measure: IHC Expression Levels of VEGF, FGF, TGFB, ALK1, CD105 and Other Markers
time frame: Baseline
description: Associated with measures of clinical response to treatment, including PFS and OS.
measure: Pre-treatment Plasma Concentration Levels of VEGF, BMP9, BMP10, and ALK1
time frame: Baseline
description: Associated with measures of clinical response to treatment, including PFS and OS.
arm group label: Treatment (dalantercept)
arm group type: Experimental
description: Patients receive dalantercept SC on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
intervention type: Biological
intervention name: Dalantercept
description: Given SC
arm group label: Treatment (dalantercept)
other name: ACE-041
other name: Activin Receptor-like Kinase 1 Inhibitor ACE-041
other name: ALK1-Fc Fusion Protein ACE-041
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (dalantercept)
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert A Burger
role: Principal Investigator
affiliation: NRG Oncology
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country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Recurrence
mesh term: Immunoglobulin Fc Fragments
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 