<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/NCT03009201</url>
  </required_header>
  <id_info>
    <org_study_id>STUDY00016070</org_study_id>
    <secondary_id>NCI-2016-01794</secondary_id>
    <secondary_id>STUDY00016070</secondary_id>
    <nct_id>NCT03009201</nct_id>
  </id_info>
  <brief_title>Ribociclib and Doxorubicin in Treating Patients With Metastatic or Advanced Soft Tissue Sarcomas That Cannot Be Removed by Surgery</brief_title>
  <official_title>A Phase 1B Study of Ribociclib in Combination With Doxorubicin in Advanced Soft Tissue Sarcomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OHSU Knight Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>OHSU Knight Cancer Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase Ib trial studies the side effects and best dose of ribociclib when giving together&#xD;
      with doxorubicin hydrochloride in treating patients with soft tissue sarcomas that has spread&#xD;
      to other places or that cannot be removed by surgery (advanced). Ribociclib may stop the&#xD;
      growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in&#xD;
      chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of&#xD;
      tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them&#xD;
      from spreading. Giving ribociclib and doxorubicin hydrochloride may work better in treating&#xD;
      patients with soft tissue sarcoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the recommended phase 2 dose (RP2D) of ribociclib in combination with&#xD;
      doxorubicin in subjects with advanced soft tissue sarcomas.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To assess preliminary anti-tumor activity of ribociclib in combination with doxorubicin in&#xD;
      subjects with advanced soft tissue sarcomas.&#xD;
&#xD;
      II. To characterize the safety and tolerability of ribociclib in combination with&#xD;
      doxorubicin.&#xD;
&#xD;
      OUTLINE: This is a dose-escalation study of ribociclib.&#xD;
&#xD;
      Patients receive ribociclib orally (PO) daily on days 1-7, and doxorubicin hydrochloride&#xD;
      intravenously (IV) on day 10. Treatment repeats every 21 days for up to 6 cycles in the&#xD;
      absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      MAINTENANCE: Patients without disease progression after 6 cycles receive ribociclib PO daily&#xD;
      on days 1-21. Cycles repeat every 28 days in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up within 30 days and then every&#xD;
      12 weeks for 12 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 10, 2017</start_date>
  <completion_date type="Actual">June 30, 2023</completion_date>
  <primary_completion_date type="Actual">October 8, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of dose limiting toxicities (DLTs) of adverse events</measure>
    <time_frame>Up to 21 days</time_frame>
    <description>Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. All adverse events (AEs) will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Serious adverse events (SAE) specific incidence and exact 95% confidence interval will be provided where appropriate.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>From first dose of protocol therapy to time of documented radiographic and/or clinical disease progression or death from any cause, whichever occurs first, assessed up to 12 months</time_frame>
    <description>The Kaplan-Meier product limit method will be used to estimate PFS of the median PFS and PFS rates at clinically relevant time points will be provided with the 90% confidence interval (CI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be defined as the proportion of patients who achieved a complete response or a partial response. Will be assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1. The ORR, along with exact two-sided 95% confidence intervals, will be reported for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events, SAEs</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Will be assessed by NCI CTCAE v 4.03. Analyses will be performed for all patients having received at least one dose of study drug. Serious adverse events, AEs will be summarized using descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of dose modifications (interruptions, reductions, intensity) due to adverse events</measure>
    <time_frame>Up to 12 months</time_frame>
    <description>Analyses will be performed for all patients having received at least one dose of study drug. AEs leading to withdrawal/dose interruptions/dose modification will be summarized using descriptive statistics.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Advanced Soft Tissue Sarcoma</condition>
  <condition>Locally Advanced Angiosarcoma</condition>
  <condition>Locally Advanced Leiomyosarcoma</condition>
  <condition>Locally Advanced Liposarcoma</condition>
  <condition>Locally Advanced Malignant Peripheral Nerve Sheath Tumor</condition>
  <condition>Locally Advanced Myxofibrosarcoma</condition>
  <condition>Locally Advanced Undifferentiated Pleomorphic Sarcoma</condition>
  <condition>Metastatic Angiosarcoma</condition>
  <condition>Metastatic Epithelioid Sarcoma</condition>
  <condition>Metastatic Fibrosarcoma</condition>
  <condition>Metastatic Liposarcoma</condition>
  <condition>Metastatic Malignant Peripheral Nerve Sheath Tumor</condition>
  <condition>Metastatic Myxofibrosarcoma</condition>
  <condition>Metastatic Soft Tissue Sarcoma</condition>
  <condition>Metastatic Synovial Sarcoma</condition>
  <condition>Metastatic Undifferentiated Pleomorphic Sarcoma</condition>
  <condition>Myxofibrosarcoma</condition>
  <condition>Pleomorphic Rhabdomyosarcoma</condition>
  <condition>Stage III Soft Tissue Sarcoma AJCC v7</condition>
  <condition>Stage IV Soft Tissue Sarcoma AJCC v7</condition>
  <condition>Undifferentiated (Embryonal) Sarcoma</condition>
  <condition>Unresectable Leiomyosarcoma</condition>
  <condition>Unresectable Liposarcoma</condition>
  <condition>Unresectable Malignant Peripheral Nerve Sheath Tumor</condition>
  <condition>Unresectable Soft Tissue Sarcoma</condition>
  <condition>Unresectable Synovial Sarcoma</condition>
  <condition>Unresectable Undifferentiated Pleomorphic Sarcoma</condition>
  <arm_group>
    <arm_group_label>Treatment (ribociclib, doxorubicin hydrochloride)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive ribociclib PO daily on days 1-7, and doxorubicin hydrochloride IV on day 10. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.&#xD;
MAINTENANCE: Patients receive ribociclib PO daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Doxorubicin Hydrochloride</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (ribociclib, doxorubicin hydrochloride)</arm_group_label>
    <other_name>5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)</other_name>
    <other_name>ADM</other_name>
    <other_name>Adriacin</other_name>
    <other_name>Adriamycin</other_name>
    <other_name>Adriamycin Hydrochloride</other_name>
    <other_name>Adriamycin PFS</other_name>
    <other_name>Adriamycin RDF</other_name>
    <other_name>ADRIAMYCIN, HYDROCHLORIDE</other_name>
    <other_name>Adriamycine</other_name>
    <other_name>Adriblastina</other_name>
    <other_name>Adriblastine</other_name>
    <other_name>Adrimedac</other_name>
    <other_name>Chloridrato de Doxorrubicina</other_name>
    <other_name>DOX</other_name>
    <other_name>DOXO-CELL</other_name>
    <other_name>Doxolem</other_name>
    <other_name>Doxorubicin HCl</other_name>
    <other_name>Doxorubicin.HCl</other_name>
    <other_name>Doxorubin</other_name>
    <other_name>Farmiblastina</other_name>
    <other_name>FI 106</other_name>
    <other_name>FI-106</other_name>
    <other_name>hydroxydaunorubicin</other_name>
    <other_name>Rubex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ribociclib, doxorubicin hydrochloride)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (ribociclib, doxorubicin hydrochloride)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ribociclib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (ribociclib, doxorubicin hydrochloride)</arm_group_label>
    <other_name>Kisqali</other_name>
    <other_name>LEE-011</other_name>
    <other_name>LEE011</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Pathologically confirmed diagnosis of intermediate or high-grade soft tissue sarcoma&#xD;
             for which single-agent doxorubicin is appropriate therapy, including but not limited&#xD;
             to:&#xD;
&#xD;
               -  Synovial sarcoma&#xD;
&#xD;
               -  Fibrosarcoma&#xD;
&#xD;
               -  Undifferentiated sarcoma&#xD;
&#xD;
               -  Liposarcoma&#xD;
&#xD;
               -  Leiomyosarcoma&#xD;
&#xD;
               -  Angiosarcoma&#xD;
&#xD;
               -  Malignant peripheral nerve sheath tumor&#xD;
&#xD;
               -  Pleomorphic rhabdomyosarcoma&#xD;
&#xD;
               -  Myxofibrosarcoma&#xD;
&#xD;
               -  Epithelioid sarcoma&#xD;
&#xD;
               -  Undifferentiated pleomorphic sarcoma&#xD;
&#xD;
          -  Locally advanced unresectable or metastatic disease with no standard curative therapy&#xD;
             available&#xD;
&#xD;
          -  Archival tumor tissue retinoblastoma-associated protein (pRb) positive by&#xD;
             immunohistochemistry (IHC)&#xD;
&#xD;
          -  Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1&#xD;
             criteria&#xD;
&#xD;
          -  All races and ethnic groups will be included; for subjects between the ages of 12-18&#xD;
             years only, body surface area (BSA) must be &gt;= 1.28 m^2&#xD;
&#xD;
          -  Ejection fraction of &gt;= 50% by echocardiogram or multi-gated acquisition (MUGA) scan&#xD;
&#xD;
          -  Female subjects of childbearing potential must have a negative urine beta-human&#xD;
             chorionic gonadotropin (beta-hCG) pregnancy test at time of screening and within 14&#xD;
             days prior to planned first dose of ribociclib&#xD;
&#xD;
          -  Willing to use adequate contraception throughout the study and for 3 weeks after study&#xD;
             drug discontinuation&#xD;
&#xD;
          -  Meets the following standard 12-lead electrocardiography (ECG) parameters at screening&#xD;
             (defined as the mean of the triplicate ECGs; ECGs done in triplicate do not have a&#xD;
             defined interval between assessments):&#xD;
&#xD;
               -  Corrected QT using Fridericia's correction formula (QTcF) interval at screening &lt;&#xD;
                  450 msec for males and &lt; 470 msec for females (using Fridericia's correction)&#xD;
&#xD;
               -  Resting heart rate =&lt; 100 beats per minute (bpm)&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1.5 K/cu mm&#xD;
&#xD;
          -  Platelets (no transfusion within prior 7 days) &gt;= 100 K/cu mm&#xD;
&#xD;
          -  Hemoglobin (no transfusion within prior 7 days) &gt;= 9.0 g/dL&#xD;
&#xD;
          -  Total bilirubin &lt; institutional upper limit of normal (ULN), except for subjects with&#xD;
             documented Gilbert's syndrome, for which =&lt; 3.0 x ULN or direct bilirubin =&lt; 1.5 x ULN&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and&#xD;
             alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT) in the&#xD;
             absence of liver metastases: =&lt; 2.5 x ULN; if the subject has liver metastases: &lt; 5 x&#xD;
             ULN&#xD;
&#xD;
          -  Serum creatinine &lt; 1.7 mg/dL&#xD;
&#xD;
          -  Potassium within institutional normal limit (WNL)&#xD;
&#xD;
          -  Corrected calcium WNL&#xD;
&#xD;
          -  Magnesium WNL&#xD;
&#xD;
          -  International normalized ratio (INR) =&lt; 1.5&#xD;
&#xD;
               -  Use of rivaroxaban, apixaban, edoxaban or warfarin is an exclusion criteria;&#xD;
                  therapy with heparin, low molecular weight heparin (LMWH), dabigatran or&#xD;
                  fondaparinux is allowed&#xD;
&#xD;
          -  All prior treatment-related toxicities resolved to =&lt; grade 1 or are determined to be&#xD;
             clinically stable by the investigator&#xD;
&#xD;
          -  Has completed prior therapies according to the criteria below:&#xD;
&#xD;
               -  Cytotoxic chemotherapy - at least 21 days since last dose prior to first dose of&#xD;
                  ribociclib&#xD;
&#xD;
               -  Small molecule inhibitors - at least 14 days since last dose prior to first dose&#xD;
                  of ribociclib&#xD;
&#xD;
               -  Monoclonal antibodies - at least 3 half-lives since last dose prior to first dose&#xD;
                  of ribociclib; exception: denosumab for bony metastases is allowable&#xD;
&#xD;
               -  Immunotherapy (e.g. tumor vaccines) - at least 42 days since last dose prior to&#xD;
                  first dose of ribociclib&#xD;
&#xD;
               -  Radiation - at least 14 days since last dose prior to first dose of ribociclib&#xD;
&#xD;
          -  Able to swallow capsules&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2 (Karnofsky &gt;= 60%)&#xD;
&#xD;
          -  Life expectancy &gt; 3 months&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document;&#xD;
             subject has signed the informed consent (ICF) prior to any screening procedures being&#xD;
             performed and is able to comply with protocol requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with low grade tumors (histologic grade 1/3)&#xD;
&#xD;
          -  Histologic diagnosis for which single-agent doxorubicin is NOT appropriate therapy,&#xD;
             including but not limited to:&#xD;
&#xD;
               -  Alveolar or embryonal rhabdomyosarcoma&#xD;
&#xD;
               -  Ewings sarcoma or primitive neuroectodermal tumor (PNET)&#xD;
&#xD;
               -  Osteosarcoma&#xD;
&#xD;
               -  Gastrointestinal stromal tumor (GIST)&#xD;
&#xD;
          -  Prior systemic therapy with an anthracycline for any indication&#xD;
&#xD;
          -  Known hypersensitivity to any of the excipients of ribociclib or doxorubicin&#xD;
             (including to peanut and soy)&#xD;
&#xD;
          -  Currently receiving any of the following that cannot be discontinued at least 7 days&#xD;
             prior to starting study drug:&#xD;
&#xD;
               -  Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit&#xD;
                  hybrids, pummelos, star-fruit, and Seville oranges&#xD;
&#xD;
               -  Medications with a narrow therapeutic window that are predominantly metabolized&#xD;
                  through CYP3A4/5&#xD;
&#xD;
               -  Herbal supplements, such as St. John's wort; the use of marijuana or its&#xD;
                  derivatives is allowed in States with statutes permitting the use of recreational&#xD;
                  or medical marijuana&#xD;
&#xD;
          -  Uncontrolled intercurrent medical condition including, but not limited to:&#xD;
&#xD;
               -  Uncontrolled infection&#xD;
&#xD;
               -  Symptomatic congestive heart failure (New York Heart Association [NYHA] class&#xD;
                  III-IV)&#xD;
&#xD;
               -  Acute coronary syndromes (including myocardial infarction, unstable angina,&#xD;
                  coronary artery bypass grafting, coronary angioplasty, or stenting) or&#xD;
                  symptomatic pericarditis within 6 months prior to screening&#xD;
&#xD;
               -  Uncontrolled cardiac arrhythmia or arrhythmia requiring medication other than&#xD;
                  beta blocker&#xD;
&#xD;
               -  Psychiatric illness/social situations that would limit compliance with study&#xD;
                  requirements&#xD;
&#xD;
               -  Any other concurrent severe and/or uncontrolled medical condition that would, in&#xD;
                  the investigator's judgment, cause unacceptable safety risks or compromise&#xD;
                  compliance with the protocol (e.g. chronic pancreatitis, chronic active&#xD;
                  hepatitis, etc.)&#xD;
&#xD;
          -  Concurrent malignancy or malignancy within 3 years prior to starting study drug,&#xD;
             except:&#xD;
&#xD;
               -  Malignancies that have completed therapy and are considered by their physician to&#xD;
                  be at less than 30% risk of relapse, or&#xD;
&#xD;
               -  Malignancies not requiring treatment (e.g., RAI stage 0 chronic lymphocytic&#xD;
                  leukemia [CLL])&#xD;
&#xD;
          -  Central nervous system (CNS) involvement unless they meet ALL of the following&#xD;
             criteria:&#xD;
&#xD;
               -  At least 4 weeks from prior therapy completion (including radiation and/or&#xD;
                  surgery) to starting the study treatment&#xD;
&#xD;
               -  Clinically stable CNS tumor at the time of screening and not receiving steroids&#xD;
                  and/or enzyme-inducing anti-epileptic medications for brain metastases&#xD;
&#xD;
          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
             alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled&#xD;
             nausea/vomiting/diarrhea, malabsorption syndrome, or major small bowel resection)&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) infection (testing not mandatory);&#xD;
             NOTE: HIV-positive subjects on combination antiretroviral therapy are ineligible&#xD;
             because of the potential for pharmacokinetic interactions with ribociclib; in&#xD;
             addition, these subjects are at increased risk of lethal infections when treated with&#xD;
             marrow suppressive therapy; appropriate studies will be undertaken in subjects&#xD;
             receiving combination antiretroviral therapy when indicated&#xD;
&#xD;
          -  Systolic blood pressure (SBP) &gt; 160 mmHg or &lt; 90 mmHg at screening; if initial&#xD;
             screening SBP is outside of the eligible range, blood pressure may be re-checked after&#xD;
             intervention; SBP must be documented as stable and within the eligible range prior to&#xD;
             starting study drug&#xD;
&#xD;
          -  Currently receiving rivaroxaban, apixaban, endoxaban, warfarin or other warfarin&#xD;
             derived anticoagulant; therapy with heparin, low molecular weight heparin (LMWH),&#xD;
             dabigatran or fondaparinux is allowed; if transitioning from a prohibited&#xD;
             anticoagulant, a minimum washout of 7 days from last dose of the prohibited medication&#xD;
             is required prior to ribociclib start&#xD;
&#xD;
          -  Participation in a prior investigational interventional study within 30 days prior to&#xD;
             enrollment or within 5 half-lives of the investigational product, whichever is longer&#xD;
&#xD;
          -  Major surgery within 14 days prior to starting study drug or has not recovered from&#xD;
             surgical complications (tumor biopsy is not considered as major surgery)&#xD;
&#xD;
          -  History of congenital long QT syndrome or torsades de pointes&#xD;
&#xD;
          -  History of non-compliance to medical regimen or inability to grant consent&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women; breastfeeding should be discontinued&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lara E Davis</last_name>
    <role>Principal Investigator</role>
    <affiliation>OHSU Knight Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>OHSU Knight Cancer Institute</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <last_update_submitted>August 14, 2023</last_update_submitted>
  <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 16, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>OHSU Knight Cancer Institute</investigator_affiliation>
    <investigator_full_name>Lara Davis, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Leiomyosarcoma</mesh_term>
    <mesh_term>Liposarcoma</mesh_term>
    <mesh_term>Sarcoma, Synovial</mesh_term>
    <mesh_term>Hemangiosarcoma</mesh_term>
    <mesh_term>Nerve Sheath Neoplasms</mesh_term>
    <mesh_term>Neurofibrosarcoma</mesh_term>
    <mesh_term>Fibrosarcoma</mesh_term>
    <mesh_term>Histiocytoma, Malignant Fibrous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Doxorubicin</mesh_term>
    <mesh_term>Liposomal doxorubicin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03009201
org study id: STUDY00016070
secondary id: NCI-2016-01794
secondary id: STUDY00016070
nct id: NCT03009201
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase Ib trial studies the side effects and best dose of ribociclib when giving together
      with doxorubicin hydrochloride in treating patients with soft tissue sarcomas that has spread
      to other places or that cannot be removed by surgery (advanced). Ribociclib may stop the
      growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of
      tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them
      from spreading. Giving ribociclib and doxorubicin hydrochloride may work better in treating
      patients with soft tissue sarcoma.
PRIMARY OBJECTIVE:

      I. To determine the recommended phase 2 dose (RP2D) of ribociclib in combination with
      doxorubicin in subjects with advanced soft tissue sarcomas.

      SECONDARY OBJECTIVES:

      I. To assess preliminary anti-tumor activity of ribociclib in combination with doxorubicin in
      subjects with advanced soft tissue sarcomas.

      II. To characterize the safety and tolerability of ribociclib in combination with
      doxorubicin.

      OUTLINE: This is a dose-escalation study of ribociclib.

      Patients receive ribociclib orally (PO) daily on days 1-7, and doxorubicin hydrochloride
      intravenously (IV) on day 10. Treatment repeats every 21 days for up to 6 cycles in the
      absence of disease progression or unacceptable toxicity.

      MAINTENANCE: Patients without disease progression after 6 cycles receive ribociclib PO daily
      on days 1-21. Cycles repeat every 28 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up within 30 days and then every
      12 weeks for 12 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of dose limiting toxicities (DLTs) of adverse events
time frame: Up to 21 days
description: Will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03. All adverse events (AEs) will be tabulated and summarized by major organ category, grade, anticipation, and drug attribution. Serious adverse events (SAE) specific incidence and exact 95% confidence interval will be provided where appropriate.
measure: Progression-free survival (PFS)
time frame: From first dose of protocol therapy to time of documented radiographic and/or clinical disease progression or death from any cause, whichever occurs first, assessed up to 12 months
description: The Kaplan-Meier product limit method will be used to estimate PFS of the median PFS and PFS rates at clinically relevant time points will be provided with the 90% confidence interval (CI).
measure: Objective response rate (ORR)
time frame: Up to 12 months
description: Will be defined as the proportion of patients who achieved a complete response or a partial response. Will be assessed based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1. The ORR, along with exact two-sided 95% confidence intervals, will be reported for the study.
measure: Incidence of adverse events, SAEs
time frame: Up to 12 months
description: Will be assessed by NCI CTCAE v 4.03. Analyses will be performed for all patients having received at least one dose of study drug. Serious adverse events, AEs will be summarized using descriptive statistics.
measure: Incidence of dose modifications (interruptions, reductions, intensity) due to adverse events
time frame: Up to 12 months
description: Analyses will be performed for all patients having received at least one dose of study drug. AEs leading to withdrawal/dose interruptions/dose modification will be summarized using descriptive statistics.
arm group label: Treatment (ribociclib, doxorubicin hydrochloride)
arm group type: Experimental
description: Patients receive ribociclib PO daily on days 1-7, and doxorubicin hydrochloride IV on day 10. Treatment repeats every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients receive ribociclib PO daily on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Doxorubicin Hydrochloride
description: Given IV
arm group label: Treatment (ribociclib, doxorubicin hydrochloride)
other name: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
other name: ADM
other name: Adriacin
other name: Adriamycin
other name: Adriamycin Hydrochloride
other name: Adriamycin PFS
other name: Adriamycin RDF
other name: ADRIAMYCIN, HYDROCHLORIDE
other name: Adriamycine
other name: Adriblastina
other name: Adriblastine
other name: Adrimedac
other name: Chloridrato de Doxorrubicina
other name: DOX
other name: DOXO-CELL
other name: Doxolem
other name: Doxorubicin HCl
other name: Doxorubicin.HCl
other name: Doxorubin
other name: Farmiblastina
other name: FI 106
other name: FI-106
other name: hydroxydaunorubicin
other name: Rubex
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (ribociclib, doxorubicin hydrochloride)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Treatment (ribociclib, doxorubicin hydrochloride)
intervention type: Drug
intervention name: Ribociclib
description: Given PO
arm group label: Treatment (ribociclib, doxorubicin hydrochloride)
other name: Kisqali
other name: LEE-011
other name: LEE011
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Lara E Davis
role: Principal Investigator
affiliation: OHSU Knight Cancer Institute
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: OHSU Knight Cancer Institute
investigator full name: Lara Davis, MD
investigator title: Principal Investigator
mesh term: Sarcoma
mesh term: Rhabdomyosarcoma
mesh term: Leiomyosarcoma
mesh term: Liposarcoma
mesh term: Sarcoma, Synovial
mesh term: Hemangiosarcoma
mesh term: Nerve Sheath Neoplasms
mesh term: Neurofibrosarcoma
mesh term: Fibrosarcoma
mesh term: Histiocytoma, Malignant Fibrous
mesh term: Doxorubicin
mesh term: Liposomal doxorubicin