<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/NCT02987959</url>
  </required_header>
  <id_info>
    <org_study_id>SAR-081</org_study_id>
    <nct_id>NCT02987959</nct_id>
  </id_info>
  <brief_title>Study of TAK-228 (MLN0128) in Soft Tissue Sarcomas</brief_title>
  <official_title>Phase II Study of TAK-228 (MLN0128) in Soft Tissue Sarcomas With Dysregulation of the mTOR Pathway</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fox Chase Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fox Chase Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label phase II study of TAK-228 for patients ≥ 18 years of age with complex&#xD;
      genomic sarcomas exhibiting Phosphoinositide-3 Kinase (PI3K) pathway dysregulation. Patients&#xD;
      must have surgically unresectable or metastatic disease that is refractory to at least one&#xD;
      prior line of therapy (not including neoadjuvant or adjuvant therapy in a curative setting).&#xD;
      Patients disease must also have evidence of progression prior to enrollment. The purpose of&#xD;
      this study is to determine the antitumor activity in this group of patients. Patients must&#xD;
      meet all eligibility criteria as detailed in section 10. A total of up to 33 patients will be&#xD;
      included in the study. Patients will undergo screening evaluations to determine eligibility&#xD;
      within 28 days of the first dose. All patients will be required to submit baseline tumor&#xD;
      samples for analysis. Patients who have had their tumors tested commercially for PI3K/&#xD;
      AKT/mechanistic Target of Rapamycin (mTOR) alterations will be assessed on a case by case&#xD;
      basis for eligibility and for determination as to whether additional tissue is required.&#xD;
&#xD;
      TAK-228 will be administered orally at 3 mg daily for a 21 day cycle. Clinical and laboratory&#xD;
      assessments will be made on day 1 of each cycle. Disease will be assessed by comparing&#xD;
      unidimensional tumor measurements on pre and peritreatment imaging (CT or MRI) after weeks 6,&#xD;
      12, 18 and every 12 weeks thereafter. Response will be assessed according to RECIST 1.1.&#xD;
      Therapy will continue until disease progression or unacceptable toxicity or withdrawal of&#xD;
      consent.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Closed to accrual due to Funding Sponsor withdrawing support due to low accrual&#xD;
  </why_stopped>
  <start_date type="Actual">February 21, 2017</start_date>
  <completion_date type="Actual">July 24, 2020</completion_date>
  <primary_completion_date type="Actual">January 30, 2019</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>The Progression Free Survival Rate With TAK-228 in Sarcoma Patients With PI3K/AKT/mTOR Pathway Dysregulation</measure>
    <time_frame>12 weeks post-treatment</time_frame>
    <description>Progression free rate will be determined by determining the number of patients with complete response, partial response and stable disease</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Rate of Toxicity of TAK-228 in This Patient Population as Per Common Terminology Criteria for Adverse Events (CTCAE)v4.03 Criteria.</measure>
    <time_frame>1 year</time_frame>
    <description>Toxicity will be assessed by calculating number of participants experiencing adverse events as per CTCAEv4.03 criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Objective Response Rate (ORR) of TAK-228 in This Patient Population.</measure>
    <time_frame>upto 4 years</time_frame>
    <description>Objective response rate will be defined as patients with complete response and partial response. As per RECIST v1.1 guidelines, complete response is defined as the disappearance of all measurable lesions, and partial response is defined as &gt;=30% decrease in sum of diameters of target lesions compared to the baseline sum of diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival in This Patient Population.</measure>
    <time_frame>upto 4 years</time_frame>
    <description>Progression Free Survival, defined as the time from initiation of treatment until disease progression will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival Rate in This Patient Population</measure>
    <time_frame>upto 4 years</time_frame>
    <description>Overall Survival, defined as the time from initiation of treatment until death from any cause will be calculated.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Soft-tissue Sarcoma</condition>
  <arm_group>
    <arm_group_label>TAK-228 treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAK-228</intervention_name>
    <description>TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
    <arm_group_label>TAK-228 treatment</arm_group_label>
    <other_name>MLN0128</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  This trial has two step inclusion criteria.&#xD;
&#xD;
        Step 1 Inclusion Criteria&#xD;
&#xD;
          1. Male or female patients 18 years or older.&#xD;
&#xD;
          2. Patients must have a diagnosis of a locally advanced or metastatic sarcoma that is&#xD;
             progressing. The following subtypes (considered genomically complex) will be eligible:&#xD;
             leiomyosarcoma (well differentiated or poorly differentiated), undifferentiated&#xD;
             pleomorphic sarcoma, myxofibrosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic&#xD;
             liposarcoma, malignant peripheral nerve sheath tumor, angiosarcoma or extraskeletal&#xD;
             osteosarcoma. Other potentially genomically complex Soft Tissue Sarcomas (STS)&#xD;
             subtypes may be included on a case-by-case basis after discussion with the principal&#xD;
             investigator.&#xD;
&#xD;
          3. Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of&#xD;
             previous radiation fields or progressed within a previous radiation field), described&#xD;
             in detail in section 15.&#xD;
&#xD;
          4. Progression of disease by radiographic imaging (10% increase in size by RECIST v1.1&#xD;
             within 6 months of registration) or presence of new lesions.&#xD;
&#xD;
          5. Must have received at least 1 prior systemic therapy for advanced disease (does not&#xD;
             include adjuvant/neoadjuvant therapy in a curative setting).&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.&#xD;
&#xD;
          7. Adequate contraception as follows:&#xD;
&#xD;
             For women:&#xD;
&#xD;
             Postmenopausal for at least 1 year before the screening visit, OR Surgically sterile,&#xD;
             OR If they are of childbearing potential, agree to practice 1 effective method of&#xD;
             contraception, and 1 additional (barrier) method, at the same time, from the time of&#xD;
             signing the informed consent through 90 days (or longer, as mandated by local labeling&#xD;
             [eg. United Surgical Partners Internationals (USPI), Summary of Product&#xD;
             Characteristics (SmPC), etc;]) after the last dose of study drug OR agree to practice&#xD;
             true abstinence, when this is in line with the preferred and usual lifestyle of the&#xD;
             patient (Periodic abstinence [e.g, calendar, ovulation, symptothermal, postovulation&#xD;
             methods] and withdrawal, spermicides only, and lactational amenorrhea are not&#xD;
             acceptable methods of contraception. Female and male condoms should not be used&#xD;
             together.)&#xD;
&#xD;
             Highly effective methods:&#xD;
&#xD;
             Intra-uterine devices (IUD) Hormonal (birth control pills/oral contraceptives,&#xD;
             injectable contraceptives, contraceptive patches, or contraceptive implants)&#xD;
&#xD;
             Other effective Methods:&#xD;
&#xD;
             Latex Condoms Diaphragm with spermicide; Cervical cap;Sponge&#xD;
&#xD;
             For men, even if surgically sterilized (ie, status post-vasectomy), they must:&#xD;
&#xD;
             Agree to practice highly effective barrier contraception during the entire study&#xD;
             treatment period and through 120 days after the last dose of study drug, OR agree to&#xD;
             practice true abstinence, when this is in line with the preferred and usual lifestyle&#xD;
             of the patient (Periodic abstinence [e.g, calendar, ovulation, symptothermal,&#xD;
             postovulation methods for the female partner] and withdrawal, spermicides only, and&#xD;
             lactational amenorrhea are not acceptable methods of contraception. Female and male&#xD;
             condoms should not be used together.)&#xD;
&#xD;
             Agree not to donate sperm during the course of this study or 120 days after receiving&#xD;
             their last dose of study drug&#xD;
&#xD;
          8. Screening clinical laboratory values as specified below:&#xD;
&#xD;
             a) Bone marrow reserve consistent with: i. absolute neutrophil count (ANC) ≥ 1.5 x&#xD;
             10(9)/L; ii. platelet count ≥ 100 x 10(9)/L; iii. hemoglobin ≥ 9 g/dL without&#xD;
             transfusion within 1 week preceding study drug administration b) Hepatic: i. total&#xD;
             bilirubin ≤ 1.5 x upper limit of normal (ULN), ii. transaminases (Aspartate&#xD;
             aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and Alanine&#xD;
             aminotransferase/Serum Glutamic Pyruvic Transaminase (ALT/SGPT) ≤ 2.5 x ULN (≤ 5 x ULN&#xD;
             if liver metastases are present); c) Renal: creatinine clearance ≥ 50 mL/min based&#xD;
             either on Cockcroft-Gault estimate or based on urine collection (12 or 24 hour); d)&#xD;
             Metabolic: i. Glycosylated hemoglobin (HbA1c) ≤ 7.0%, ii. fasting serum glucose ≤ 130&#xD;
             mg/dL iii. fasting triglycerides ≤ 300 mg/dL&#xD;
&#xD;
          9. Ability to swallow oral medications.&#xD;
&#xD;
         10. Voluntary written consent must be given before performance of any study related&#xD;
             procedure not part of standard medical care, with the understanding that consent may&#xD;
             be withdrawn by the patient at any time without prejudice to future medical care.&#xD;
&#xD;
         11. Patients who have a history of brain metastasis are eligible for the study provided&#xD;
             that all the following criteria are met:&#xD;
&#xD;
               1. Brain metastases which have been treated&#xD;
&#xD;
               2. No evidence of disease progression for ≥ 3 months or hemorrhage after treatment&#xD;
&#xD;
               3. Off-treatment with dexamethasone for 4 weeks before administration of the first&#xD;
                  dose of TAK-228&#xD;
&#xD;
               4. No ongoing requirement for dexamethasone or anti-epileptic drugs&#xD;
&#xD;
        Step 2 Inclusion Criteria: Must be met after meeting step1inclusion and exclusion criteria.&#xD;
&#xD;
        1. Tumor must have dysregulation of the PI3K/AKT/mTOR pathway. For the purposes of this&#xD;
        study, patients must have either PTEN protein or genomic loss, or&#xD;
        phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)/&#xD;
        Phosphatase and tensin homolog (PTEN) mutation. Patients must be willing to provide&#xD;
        sufficient archival tissue. If this is not available fresh tumor for biopsy is required. In&#xD;
        the event that a patient has had tumor analyzed for PTEN/PIK3CA status through commercial&#xD;
        means, their eligibility and need for additional tissue will be determined on a case by&#xD;
        case basis by the principle investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Step 1 Exclusion Criteria&#xD;
&#xD;
               1. Any clinically significant co-morbidities, such as uncontrolled pulmonary&#xD;
                  disease, active central nervous system disease, active infection, or any other&#xD;
                  condition that could compromise the patient's participation in the study.&#xD;
&#xD;
               2. Known human immunodeficiency virus infection.&#xD;
&#xD;
               3. Known hepatitis B surface antigen-positive, or known or suspected active&#xD;
                  hepatitis C infection.&#xD;
&#xD;
               4. Any serious medical or psychiatric illness that could, in the investigator's&#xD;
                  opinion, potentially interfere with the completion of treatment according to this&#xD;
                  protocol.&#xD;
&#xD;
               5. Diagnosed or treated for another malignancy within 2 years before administration&#xD;
                  of the first dose of study drug, or previously diagnosed with another malignancy&#xD;
                  and have any evidence of residual disease. Patients with nonmelanoma skin cancer&#xD;
                  or carcinoma in situ of any type are not excluded if they have undergone complete&#xD;
                  resection.&#xD;
&#xD;
               6. Breast feeding or pregnant.&#xD;
&#xD;
               7. Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI&#xD;
                  disease, or for an unknown reason that may alter the absorption of TAK-228. In&#xD;
                  addition, patients with enteric stomata are also excluded.&#xD;
&#xD;
               8. Treatment with any investigational products, radiation therapy, surgery, tumor&#xD;
                  embolization, chemotherapy or immunotherapy within 21 days before the first dose&#xD;
                  of the study drug. For biologic or hormonal therapy treatment within 14 days or&#xD;
                  five half-lives of a drug (whichever is longer) before the first dose of study&#xD;
                  drug.&#xD;
&#xD;
               9. History of any of the following within the last 6 months before administration of&#xD;
                  the first dose of the drug:&#xD;
&#xD;
                    1. Ischemic myocardial event, including angina requiring therapy and artery&#xD;
                       revascularization procedures&#xD;
&#xD;
                    2. Ischemic cerebrovascular event, including transient ischemic attack and&#xD;
                       artery revascularization procedures&#xD;
&#xD;
                    3. Requirement for inotropic support (excluding digoxin) or serious&#xD;
                       (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation,&#xD;
                       ventricular fibrillation or ventricular tachycardia)&#xD;
&#xD;
                    4. Placement of a pacemaker for control of rhythm&#xD;
&#xD;
                    5. New York Heart Association (NYHA) Class III or IV heart failure&#xD;
&#xD;
                    6. Pulmonary embolism&#xD;
&#xD;
              10. Significant active cardiovascular or pulmonary disease including:&#xD;
&#xD;
                    1. Uncontrolled hypertension (i.e., systolic blood pressure &gt;180 mm Hg,&#xD;
                       diastolic blood pressure &gt;95 mm Hg). Use of anti-hypertensive agents to&#xD;
                       control hypertension before Cycle1 Day 1 is allowed.&#xD;
&#xD;
                    2. Pulmonary hypertension&#xD;
&#xD;
                    3. Uncontrolled asthma or O2 saturation &lt; 90% by arterial blood gas analysis or&#xD;
                       pulse oximetry on room air&#xD;
&#xD;
                    4. Significant valvular disease; severe regurgitation or stenosis by imaging&#xD;
                       independent of symptom control with medical intervention, or history of&#xD;
                       valve replacement&#xD;
&#xD;
                    5. Medically significant (symptomatic) bradycardia&#xD;
&#xD;
                    6. History of arrhythmia requiring an implantable cardiac defibrillator&#xD;
&#xD;
                    7. Baseline prolongation of the rate-corrected QT interval (QTc) (e.g.,&#xD;
                       repeated demonstration of QTc interval &gt;480 milliseconds, or history of&#xD;
                       congenital long QT syndrome, or torsades de pointes)&#xD;
&#xD;
              11. Poorly controlled diabetes mellitus defined as glycosylated hemoglobin (HbA1c)&#xD;
                  &gt;7% ; patients with a history of transient glucose intolerance due to&#xD;
                  corticosteroid administration or gestational diabetes may be enrolled in this&#xD;
                  study if all other inclusion/exclusion criteria are met.&#xD;
&#xD;
              12. Treatment with strong inhibitors and/or inducers of cytochrome P450 (CYP) 3A4,&#xD;
                  CYP2C19 or CYP2C9 within 1 week preceding the first dose of study drug.&#xD;
&#xD;
              13. Patients receiving systemic corticosteroids (either IV or oral steroids,&#xD;
                  excluding inhalers or low-dose hormone replacement therapy) within 1 week before&#xD;
                  administration of the first dose of study drug.&#xD;
&#xD;
              14. Daily or chronic use of a proton pump inhibitor (PPI) and/or having taken a PPI&#xD;
                  within 7 days before receiving the first dose of study drug.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>December 2, 2016</study_first_submitted>
  <study_first_submitted_qc>December 7, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 9, 2016</study_first_posted>
  <results_first_submitted>August 7, 2020</results_first_submitted>
  <results_first_submitted_qc>February 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 24, 2021</results_first_posted>
  <last_update_submitted>September 19, 2022</last_update_submitted>
  <last_update_submitted_qc>September 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>TAK-228</keyword>
  <keyword>MLN0128</keyword>
  <keyword>mTOR</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT02987959/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 1, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/59/NCT02987959/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>TAK-228 Treatment</title>
          <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Grantor stopped supply of drugs</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TAK-228 Treatment</title>
          <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53" lower_limit="27" upper_limit="79"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tumor type</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Leiomyosarcoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Extraskeletal osteosarcoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Soft tissue sarcoma</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Progression Free Survival Rate With TAK-228 in Sarcoma Patients With PI3K/AKT/mTOR Pathway Dysregulation</title>
        <description>Progression free rate will be determined by determining the number of patients with complete response, partial response and stable disease</description>
        <time_frame>12 weeks post-treatment</time_frame>
        <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
        <group_list>
          <group group_id="O1">
            <title>TAK-228 Treatment</title>
            <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
          </group>
        </group_list>
        <measure>
          <title>The Progression Free Survival Rate With TAK-228 in Sarcoma Patients With PI3K/AKT/mTOR Pathway Dysregulation</title>
          <description>Progression free rate will be determined by determining the number of patients with complete response, partial response and stable disease</description>
          <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Rate of Toxicity of TAK-228 in This Patient Population as Per Common Terminology Criteria for Adverse Events (CTCAE)v4.03 Criteria.</title>
        <description>Toxicity will be assessed by calculating number of participants experiencing adverse events as per CTCAEv4.03 criteria</description>
        <time_frame>1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TAK-228 Treatment</title>
            <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
          </group>
        </group_list>
        <measure>
          <title>The Rate of Toxicity of TAK-228 in This Patient Population as Per Common Terminology Criteria for Adverse Events (CTCAE)v4.03 Criteria.</title>
          <description>Toxicity will be assessed by calculating number of participants experiencing adverse events as per CTCAEv4.03 criteria</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Objective Response Rate (ORR) of TAK-228 in This Patient Population.</title>
        <description>Objective response rate will be defined as patients with complete response and partial response. As per RECIST v1.1 guidelines, complete response is defined as the disappearance of all measurable lesions, and partial response is defined as &gt;=30% decrease in sum of diameters of target lesions compared to the baseline sum of diameters.</description>
        <time_frame>upto 4 years</time_frame>
        <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
        <group_list>
          <group group_id="O1">
            <title>TAK-228 Treatment</title>
            <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
          </group>
        </group_list>
        <measure>
          <title>The Objective Response Rate (ORR) of TAK-228 in This Patient Population.</title>
          <description>Objective response rate will be defined as patients with complete response and partial response. As per RECIST v1.1 guidelines, complete response is defined as the disappearance of all measurable lesions, and partial response is defined as &gt;=30% decrease in sum of diameters of target lesions compared to the baseline sum of diameters.</description>
          <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival in This Patient Population.</title>
        <description>Progression Free Survival, defined as the time from initiation of treatment until disease progression will be calculated.</description>
        <time_frame>upto 4 years</time_frame>
        <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
        <group_list>
          <group group_id="O1">
            <title>TAK-228 Treatment</title>
            <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival in This Patient Population.</title>
          <description>Progression Free Survival, defined as the time from initiation of treatment until disease progression will be calculated.</description>
          <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival Rate in This Patient Population</title>
        <description>Overall Survival, defined as the time from initiation of treatment until death from any cause will be calculated.</description>
        <time_frame>upto 4 years</time_frame>
        <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
        <group_list>
          <group group_id="O1">
            <title>TAK-228 Treatment</title>
            <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival Rate in This Patient Population</title>
          <description>Overall Survival, defined as the time from initiation of treatment until death from any cause will be calculated.</description>
          <population>Insufficient number of patients accrued for a meaningful analysis. No data collected from any participant.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 year</time_frame>
      <group_list>
        <group group_id="E1">
          <title>TAK-228 Treatment</title>
          <description>Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228&#xD;
TAK-228: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intractable nausea and vomiting</sub_title>
                <description>Patient was hospitalized after 4 days of nausea and vomiting with some loose stools</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Septic arthritis</sub_title>
                <description>Grade 3 septic arthritis in the knee</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <description>Grade 3 acute kidney injury</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <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="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <description>Anemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <description>Light headedness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <description>Palpitations</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <description>Eye itching</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Taste alteration</sub_title>
                <description>Gastrointestinal disorders - Other</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Edema</sub_title>
                <description>Edema limbs</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infections and infestations - Other, specify</sub_title>
                <description>Infection</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wound complication</sub_title>
                <description>Wound right knee</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <description>Discomfort anterior portion right leg Sweats</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <description>Activated partial thromboplastin time prolonged</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <description>Alanine aminotransferase increased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <description>Weight loss</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <description>White blood cell decreased</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <description>Anorexia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <description>Hyperglycemia</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <description>Myalgia</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <description>Back pain</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <description>Generalized muscle weakness</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Right hip cramps</sub_title>
                <description>Musculoskeletal and connective tissue disorder - Other, specify</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>Dizziness</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>Headache</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <description>Syncope</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <description>Tremor</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <description>Depression</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <description>Proteinuria</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <description>Dyspnea</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <description>Cough</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <description>Epistaxis</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <description>Nasal congestion</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, specify</sub_title>
                <description>Shortness of breath</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <description>Rash maculo-papular</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <description>Itching and hives</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <description>Dry skin</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <description>Pruritus</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Protocol Developer</name_or_title>
      <organization>Fox Chase Cancer Center</organization>
      <phone>215-728-4097</phone>
      <email>ryan.romasko@fccc.edu</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/NCT02987959
org study id: SAR-081
nct id: NCT02987959
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label phase II study of TAK-228 for patients ≥ 18 years of age with complex
      genomic sarcomas exhibiting Phosphoinositide-3 Kinase (PI3K) pathway dysregulation. Patients
      must have surgically unresectable or metastatic disease that is refractory to at least one
      prior line of therapy (not including neoadjuvant or adjuvant therapy in a curative setting).
      Patients disease must also have evidence of progression prior to enrollment. The purpose of
      this study is to determine the antitumor activity in this group of patients. Patients must
      meet all eligibility criteria as detailed in section 10. A total of up to 33 patients will be
      included in the study. Patients will undergo screening evaluations to determine eligibility
      within 28 days of the first dose. All patients will be required to submit baseline tumor
      samples for analysis. Patients who have had their tumors tested commercially for PI3K/
      AKT/mechanistic Target of Rapamycin (mTOR) alterations will be assessed on a case by case
      basis for eligibility and for determination as to whether additional tissue is required.

      TAK-228 will be administered orally at 3 mg daily for a 21 day cycle. Clinical and laboratory
      assessments will be made on day 1 of each cycle. Disease will be assessed by comparing
      unidimensional tumor measurements on pre and peritreatment imaging (CT or MRI) after weeks 6,
      12, 18 and every 12 weeks thereafter. Response will be assessed according to RECIST 1.1.
      Therapy will continue until disease progression or unacceptable toxicity or withdrawal of
      consent.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The Progression Free Survival Rate With TAK-228 in Sarcoma Patients With PI3K/AKT/mTOR Pathway Dysregulation
time frame: 12 weeks post-treatment
description: Progression free rate will be determined by determining the number of patients with complete response, partial response and stable disease
measure: The Rate of Toxicity of TAK-228 in This Patient Population as Per Common Terminology Criteria for Adverse Events (CTCAE)v4.03 Criteria.
time frame: 1 year
description: Toxicity will be assessed by calculating number of participants experiencing adverse events as per CTCAEv4.03 criteria
measure: The Objective Response Rate (ORR) of TAK-228 in This Patient Population.
time frame: upto 4 years
description: Objective response rate will be defined as patients with complete response and partial response. As per RECIST v1.1 guidelines, complete response is defined as the disappearance of all measurable lesions, and partial response is defined as >=30% decrease in sum of diameters of target lesions compared to the baseline sum of diameters.
measure: Progression Free Survival in This Patient Population.
time frame: upto 4 years
description: Progression Free Survival, defined as the time from initiation of treatment until disease progression will be calculated.
measure: Overall Survival Rate in This Patient Population
time frame: upto 4 years
description: Overall Survival, defined as the time from initiation of treatment until death from any cause will be calculated.
arm group label: TAK-228 treatment
arm group type: Experimental
description: Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228
intervention type: Drug
intervention name: TAK-228
description: TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).
arm group label: TAK-228 treatment
other name: MLN0128
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Sarcoma
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 