xml: <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/NCT06025747</url>
    </required_header>
    <id_info>
      <org_study_id>RG1123382</org_study_id>
      <secondary_id>NCI-2023-05595</secondary_id>
      <secondary_id>RG1123382</secondary_id>
      <nct_id>NCT06025747</nct_id>
    </id_info>
    <brief_title>Evaluation of Abemaciclib and Radiation Therapy Before Surgery for the Treatment of High-Risk Adipocytic Retroperitoneal Sarcoma</brief_title>
    <official_title>A Phase 1 Study of Neoadjuvant Abemaciclib in Combination With Radiation Therapy for High-Risk Adipocytic Retroperitoneal Sarcomas</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Washington</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Eli Lilly and Company</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Washington</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase I trial tests the safety, side effects, and best dose of abemaciclib and how well&#xD;
        it works with radiation therapy before surgery in treating patients with high-risk adipocytic&#xD;
        retroperitoneal sarcoma. Abemaciclib may stop the growth of tumor cells by blocking some of&#xD;
        the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor&#xD;
        cells and shrink tumors. Giving abemaciclib together with radiation therapy before surgery&#xD;
        may shrink tumors in patients with high-risk adipocytic retroperitoneal sarcoma.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        OUTLINE: This is a dose-escalation study of abemaciclib.&#xD;
  &#xD;
        Prior to surgery, patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28.&#xD;
        Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or&#xD;
        unacceptable toxicity. Patients undergo radiation therapy over 28 fractions starting on cycle&#xD;
        1 day 15 in the absence of disease progression or unacceptable toxicity. After completion of&#xD;
        radiation therapy, patients may undergo surgery. Patients also undergo computed tomography&#xD;
        (CT) or magnetic resonance imaging (MRI) during screening and on study.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up at 30 days.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">March 3, 2026</completion_date>
    <primary_completion_date type="Anticipated">March 3, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Recommended phase 2 dose of abemaciclib in combination with radiation</measure>
      <time_frame>Up to 28 days</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Rate of pathologic response</measure>
      <time_frame>Up to 2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of surgical excision with negative margins</measure>
      <time_frame>Up to 2 years</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events</measure>
      <time_frame>Up to 30 days post treatment</time_frame>
      <description>Will be assessed by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of discontinuation of abemaciclib monotherapy</measure>
      <time_frame>Within the first 15 days (+7 days) of Cycle 1 Day 1 (Cycle is 28 days)</time_frame>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Retroperitoneal Sarcoma</condition>
    <arm_group>
      <arm_group_label>Treatment (abemaciclib, radiation therapy, surgery)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Prior to surgery, patients receive abemaciclib orally PO BID on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy over 28 fractions starting on cycle 1 day 15 in the absence of disease progression or unacceptable toxicity. After completion of radiation therapy, patients may undergo surgery. Patients also undergo CT or MRI during screening and on study.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Abemaciclib</intervention_name>
      <description>Given PO</description>
      <arm_group_label>Treatment (abemaciclib, radiation therapy, surgery)</arm_group_label>
      <other_name>LY-2835219</other_name>
      <other_name>LY2835219</other_name>
      <other_name>Verzenio</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT</description>
      <arm_group_label>Treatment (abemaciclib, radiation therapy, surgery)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Magnetic Resonance Imaging</intervention_name>
      <description>Undergo MRI</description>
      <arm_group_label>Treatment (abemaciclib, radiation therapy, surgery)</arm_group_label>
      <other_name>Magnetic Resonance</other_name>
      <other_name>Magnetic resonance imaging (procedure)</other_name>
      <other_name>Magnetic Resonance Imaging Scan</other_name>
      <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
      <other_name>MR</other_name>
      <other_name>MR Imaging</other_name>
      <other_name>MRI</other_name>
      <other_name>MRI Scan</other_name>
      <other_name>NMR Imaging</other_name>
      <other_name>NMRI</other_name>
      <other_name>Nuclear Magnetic Resonance Imaging</other_name>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>Radiation Therapy</intervention_name>
      <description>Undergo radiation therapy</description>
      <arm_group_label>Treatment (abemaciclib, radiation therapy, surgery)</arm_group_label>
      <other_name>Cancer Radiotherapy</other_name>
      <other_name>Energy Type</other_name>
      <other_name>ENERGY_TYPE</other_name>
      <other_name>Irradiate</other_name>
      <other_name>Irradiated</other_name>
      <other_name>Irradiation</other_name>
      <other_name>Radiation</other_name>
      <other_name>Radiation Therapy, NOS</other_name>
      <other_name>Radiotherapeutics</other_name>
      <other_name>Radiotherapy</other_name>
      <other_name>RT</other_name>
      <other_name>Therapy, Radiation</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Therapeutic Surgical Procedure</intervention_name>
      <description>Undergo surgery</description>
      <arm_group_label>Treatment (abemaciclib, radiation therapy, surgery)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Subjects, &gt;= 18 years old, must have newly diagnosed or locally recurrent MDM2 or&#xD;
               CDK4-amplified adipocytic sarcoma as determined by fluorescence in situ hybridization&#xD;
               (FISH), or other clinically appropriate methodology in the opinion of the reviewing&#xD;
               pathologist. Histologic or imaging evidence of the presence of a dedifferentiated&#xD;
               component must be present&#xD;
  &#xD;
            -  Subjects must have one or more measurable target lesions by Response Evaluation&#xD;
               Criteria in Solid Tumors version 1.1 (RECIST v1.1), assessed via CT scan or MRI&#xD;
  &#xD;
            -  At the time of study enrollment, subjects must have a tumor burden that is judged to&#xD;
               be surgically resectable&#xD;
  &#xD;
            -  Have plans to undergo neoadjuvant radiation therapy followed by surgical resection.&#xD;
               Review and approval of final treatment plans for subjects receiving radiotherapy&#xD;
               locally/at an outside institution must be reviewed and approved by a radiation&#xD;
               oncologist investigator prior to initiation of radiotherapy&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3 (&gt;= 1.5 GI/L) without granulocyte&#xD;
               colony-stimulating factor support in the last 14 days&#xD;
  &#xD;
            -  White blood cell count &gt;= 2500/mm^3 (&gt;= 2.5 GI/L) (subjects may not have received&#xD;
               blood product transfusion or granulocyte colony-stimulating factor [G-CSF] within 14&#xD;
               days prior to screening)&#xD;
  &#xD;
            -  Platelets &gt;= 100,000/mm^3 (&gt;= 100 GI/L) (subjects may not have received blood product&#xD;
               transfusion or G-CSF within 14 days prior to screening)&#xD;
  &#xD;
            -  Hemoglobin &gt;= 8 g/dL (&gt;= 80 g/L) (subjects may not have received blood product&#xD;
               transfusion or G-CSF within 14 days prior to screening)&#xD;
  &#xD;
            -  Alanine aminotransferase (ALT), aspartate aminotransferase (AST) =&lt; 3 x upper limit of&#xD;
               normal (ULN) (subjects may not have received blood product transfusion or G-CSF within&#xD;
               14 days prior to screening)&#xD;
  &#xD;
            -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN) (subjects with Gilbert's disease&#xD;
               =&lt; 2 x ULN and direct bilirubin within normal limits are permitted) (subjects may not&#xD;
               have received blood product transfusion or G-CSF within 14 days prior to screening)&#xD;
  &#xD;
            -  Serum albumin &gt;= 2.8 g/dl (subjects may not have received blood product transfusion or&#xD;
               G-CSF within 14 days prior to screening)&#xD;
  &#xD;
            -  Serum creatinine =&lt; 2.0 x ULN or calculated creatinine clearance &gt;= 30 mL/min (&gt;= 0.5&#xD;
               mL/sec) using the Cockcroft-Gault equation (subjects may not have received blood&#xD;
               product transfusion or G-CSF within 14 days prior to screening)&#xD;
  &#xD;
            -  Urine protein/creatinine ratio (UPCR) =&lt; 1 mg/mg (=&lt; 113.2 mg/mmol) (subjects may not&#xD;
               have received blood product transfusion or G-CSF within 14 days prior to screening)&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
  &#xD;
            -  Male or non-pregnant and non-breast feeding female:&#xD;
  &#xD;
                 -  Women of child-bearing potential (WOCBP) must agree to use highly effective&#xD;
                    contraception without interruption from initiation of therapy and continue until&#xD;
                    4 months (120 days) after last dose of study therapy. WOCBP must have a negative&#xD;
                    serum pregnancy test (beta-human chorionic gonadotropin [hCG]) result at&#xD;
                    screening and agree to ongoing pregnancy testing during the study, and at the end&#xD;
                    of study treatment. A highly effective method of contraception is defined as one&#xD;
                    that results in a low failure rate (that is, &lt; 1% per year), when used&#xD;
                    consistently and correctly, such as implants, injectables, combined oral&#xD;
                    contraceptives, some intrauterine contraceptive devices, sexual abstinence, or a&#xD;
                    vasectomized partner&#xD;
  &#xD;
                 -  Male subjects must practice abstinence or agree to use a condom during sexual&#xD;
                    contact with a pregnant female or a female of childbearing potential while&#xD;
                    participating in the study&#xD;
  &#xD;
            -  Life expectancy of &gt; 3 months, as determined by the investigator&#xD;
  &#xD;
            -  Ability to understand and sign informed consent&#xD;
  &#xD;
            -  Willingness and ability to comply with scheduled visits, laboratory tests, and other&#xD;
               study procedures&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy&#xD;
               (including investigational) for the investigational diagnosis&#xD;
  &#xD;
            -  Receipt of any prior radiation therapy for any reason to the affected area&#xD;
  &#xD;
            -  Known central nervous system (CNS) metastases&#xD;
  &#xD;
            -  Evidence of distant metastatic disease at time of treatment initiation&#xD;
  &#xD;
            -  History of thromboembolic event within 1 year of treatment initiation. Thromboembolic&#xD;
               events include, but are not limited to, deep vein thrombosis, pulmonary embolism,&#xD;
               pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary&#xD;
               vein thrombosis, and inferior vena cava thrombosis&#xD;
  &#xD;
            -  History of any of the following conditions: syncope of cardiovascular etiology,&#xD;
               ventricular arrhythmia of pathological origin (including, but not limited to,&#xD;
               ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest&#xD;
  &#xD;
            -  History of any major surgery within 14 days prior to enrollment&#xD;
  &#xD;
            -  Receipt of ongoing anti-coagulation for treatment or prophylaxis of thromboembolic&#xD;
               event in the setting of prior thromboembolic event&#xD;
  &#xD;
            -  History of interstitial lung disease&#xD;
  &#xD;
            -  Subjects with serious and/or uncontrolled preexisting medical condition(s) that, in&#xD;
               the judgment of the investigator, would preclude participation in this study (for&#xD;
               example, interstitial lung disease, severe dyspnea at rest or requiring oxygen&#xD;
               therapy, severe renal impairment [e.g. estimated creatinine clearance &lt; 30ml/min],&#xD;
               history of major surgical resection involving the stomach or small bowel, or&#xD;
               preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition&#xD;
               resulting in baseline grade 2 or higher diarrhea)&#xD;
  &#xD;
            -  Pregnant or lactating females&#xD;
  &#xD;
            -  Inability to swallow tablets&#xD;
  &#xD;
            -  Previously identified allergy or hypersensitivity to components of the study treatment&#xD;
               formulations&#xD;
  &#xD;
            -  Diagnosis of another malignancy within 2 years before first dose of study treatment,&#xD;
               except for superficial skin cancers, or localized tumors deemed cured and not treated&#xD;
               with systemic therapy&#xD;
  &#xD;
            -  Concurrent use of medications (especially those interacting with CYP3A) that&#xD;
               potentially interact unsafely with abemaciclib which cannot be discontinued or&#xD;
               substituted&#xD;
  &#xD;
            -  Recent infection requiring systemic anti-infective treatment that was completed =&lt; 14&#xD;
               days prior to enrollment (except for uncomplicated urinary tract infection or upper&#xD;
               respiratory tract infection). Any active systemic bacterial infection (requiring&#xD;
               intravenous [IV] antibiotics at time of initiating study treatment), fungal infection,&#xD;
               or detectable viral infection (such as known human immunodeficiency virus positivity&#xD;
               or with known active hepatitis B or C [for example, hepatitis B surface antigen&#xD;
               positive]. Screening for human immunodeficiency virus (HIV)/hepatitis is not required&#xD;
               for enrollment&#xD;
  &#xD;
            -  Concurrent enrollment in any other type of medical research (for example: medical&#xD;
               device) judged by the investigator not to be scientifically or medically compatible&#xD;
               with this study&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lee Cranmer</last_name>
      <role>Principal Investigator</role>
      <affiliation>Fred Hutch/University of Washington Cancer Consortium</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Roxanne Moore</last_name>
      <phone>206-606-6425</phone>
      <email>sarcomaresearch@fredhutch.org</email>
    </overall_contact>
    <location>
      <facility>
        <name>Fred Hutch/University of Washington Cancer Consortium</name>
        <address>
          <city>Seattle</city>
          <state>Washington</state>
          <zip>98109</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Roxanne Moore</last_name>
        <phone>206-606-6425</phone>
        <email>sarcomaresearch@fredhutch.org</email>
      </contact>
      <investigator>
        <last_name>Lee Cranmer</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 6, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sarcoma</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06025747
  org study id: RG1123382
  secondary id: NCI-2023-05595
  secondary id: RG1123382
  nct id: NCT06025747
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This phase I trial tests the safety, side effects, and best dose of abemaciclib and how well
        it works with radiation therapy before surgery in treating patients with high-risk adipocytic
        retroperitoneal sarcoma. Abemaciclib may stop the growth of tumor cells by blocking some of
        the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor
        cells and shrink tumors. Giving abemaciclib together with radiation therapy before surgery
        may shrink tumors in patients with high-risk adipocytic retroperitoneal sarcoma.
  OUTLINE: This is a dose-escalation study of abemaciclib.
  
        Prior to surgery, patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28.
        Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or
        unacceptable toxicity. Patients undergo radiation therapy over 28 fractions starting on cycle
        1 day 15 in the absence of disease progression or unacceptable toxicity. After completion of
        radiation therapy, patients may undergo surgery. Patients also undergo computed tomography
        (CT) or magnetic resonance imaging (MRI) during screening and on study.
  
        After completion of study treatment, patients are followed up at 30 days.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Recommended phase 2 dose of abemaciclib in combination with radiation
  time frame: Up to 28 days
  measure: Rate of pathologic response
  time frame: Up to 2 years
  measure: Rate of surgical excision with negative margins
  time frame: Up to 2 years
  measure: Incidence of adverse events
  time frame: Up to 30 days post treatment
  description: Will be assessed by National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
  measure: Rate of discontinuation of abemaciclib monotherapy
  time frame: Within the first 15 days (+7 days) of Cycle 1 Day 1 (Cycle is 28 days)
  arm group label: Treatment (abemaciclib, radiation therapy, surgery)
  arm group type: Experimental
  description: Prior to surgery, patients receive abemaciclib orally PO BID on days 1-28. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo radiation therapy over 28 fractions starting on cycle 1 day 15 in the absence of disease progression or unacceptable toxicity. After completion of radiation therapy, patients may undergo surgery. Patients also undergo CT or MRI during screening and on study.
  intervention type: Drug
  intervention name: Abemaciclib
  description: Given PO
  arm group label: Treatment (abemaciclib, radiation therapy, surgery)
  other name: LY-2835219
  other name: LY2835219
  other name: Verzenio
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT
  arm group label: Treatment (abemaciclib, radiation therapy, surgery)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Procedure
  intervention name: Magnetic Resonance Imaging
  description: Undergo MRI
  arm group label: Treatment (abemaciclib, radiation therapy, surgery)
  other name: Magnetic Resonance
  other name: Magnetic resonance imaging (procedure)
  other name: Magnetic Resonance Imaging Scan
  other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  other name: MR
  other name: MR Imaging
  other name: MRI
  other name: MRI Scan
  other name: NMR Imaging
  other name: NMRI
  other name: Nuclear Magnetic Resonance Imaging
  intervention type: Radiation
  intervention name: Radiation Therapy
  description: Undergo radiation therapy
  arm group label: Treatment (abemaciclib, radiation therapy, surgery)
  other name: Cancer Radiotherapy
  other name: Energy Type
  other name: ENERGY_TYPE
  other name: Irradiate
  other name: Irradiated
  other name: Irradiation
  other name: Radiation
  other name: Radiation Therapy, NOS
  other name: Radiotherapeutics
  other name: Radiotherapy
  other name: RT
  other name: Therapy, Radiation
  intervention type: Procedure
  intervention name: Therapeutic Surgical Procedure
  description: Undergo surgery
  arm group label: Treatment (abemaciclib, radiation therapy, surgery)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lee Cranmer
  role: Principal Investigator
  affiliation: Fred Hutch/University of Washington Cancer Consortium
  last name: Roxanne Moore
  phone: 206-606-6425
  email: sarcomaresearch@fredhutch.org
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Sarcoma
  sharing ipd: No