<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/NCT02981940</url>
  </required_header>
  <id_info>
    <org_study_id>16-383</org_study_id>
    <nct_id>NCT02981940</nct_id>
  </id_info>
  <brief_title>A Study of Abemaciclib in Recurrent Glioblastoma</brief_title>
  <official_title>A Phase 0/2 Study of Abemaciclib in Recurrent Glioblastoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dana-Farber Cancer Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Dana-Farber 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 research study is studying a targeted therapy as a possible treatment for recurrent&#xD;
      glioblastoma (GBM).&#xD;
&#xD;
      The following intervention will be used in this study:&#xD;
&#xD;
      -Abemaciclib&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This research study is a Phase 0/II clinical trial. Phase 0 clinical trials use only a few&#xD;
      small doses of a drug. Phase II clinical trials test the safety and effectiveness of an&#xD;
      investigational drug to learn whether the drug works in treating a specific disease.&#xD;
      &quot;Investigational&quot; means that the drug is being studied.&#xD;
&#xD;
      The FDA (the U.S. Food and Drug Administration) has not approved abemaciclib as a treatment&#xD;
      for any disease.&#xD;
&#xD;
      Many brain cancers show over expression of a protein called cyclin D1. That means that the&#xD;
      body makes too much cyclin D1, which affects enzymes called CDK 4 and CDK 6. Enzymes are&#xD;
      substances in the body that help reactions between cells happen. Too much cyclin D1 triggers&#xD;
      CDK 4 and CDK 6 to make more cells than normal. This extra cell production leads to the&#xD;
      growth of tumors.&#xD;
&#xD;
      In laboratory studies, Abemaciclib was able to enter the brain, stop CDK 4 and CDK 6 from&#xD;
      making cells, and slow growth of mice Glioblastoma.&#xD;
&#xD;
      In this research study, the investigators are looking to see how safe and effect Abemaciclib&#xD;
      is with the participant type of cancer. In the surgical participants, the investigators are&#xD;
      looking to see if Abemaciclib reached the brain tumor.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 9, 2017</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Intratumoral abemaciclib concentration</measure>
    <time_frame>2 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>6-Month Progression Free Survival (PFS6)</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>pRB expression level of tumor tissue</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>2 years</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>4 months</time_frame>
    <description>PK measurements expressed as Area under the plasma concentration versus time curve (AUC) of Abemaciclib [Time Frame C1D1 (pre-treatment), C2D1, C3D1 and C4D1 (each cycle is 28 days)].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>4 months</time_frame>
    <description>PK measurements expressed as Peak Plasma Concentration (Cmax) of Abemaciclib [Time Frame C1D1 (pre-treatment), C2D1, C3D1 and C4D1 (each cycle is 28 days)]</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Response Rate</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Progression Free Survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>2 years</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Glioblastoma</condition>
  <arm_group>
    <arm_group_label>Abemaciclib with Surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Abemaciclib will be administered on a continuous twice daily dosing schedule&#xD;
Patients who require re-operation will receive a short preoperative course of Abemaciclib&#xD;
Tissue will be used to investigate the ability of Abemaciclib to pass through the blood brain barrier.&#xD;
After recovery from surgery, participants will resume Abemaciclib. Each cycle lasts 28 days.&#xD;
NOTE: enrollment to this arm is complete</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Abemaciclib without Surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Abemaciclib will be administered on a continuous twice daily dosing schedule. Each Cycle last 28 days.&#xD;
NOTE: enrollment to this arm is complete</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1 Surgery Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who require reoperation will be treated with abemaciclib for 10-14 days prior to surgery. Tissue will be used to further investigate the abilities of Abemaciclib. After surgery participants will come off study and pursue standard of care treatments at their treating physician's discretion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abemaciclib</intervention_name>
    <description>Abemaciclib capsule</description>
    <arm_group_label>Abemaciclib with Surgery</arm_group_label>
    <arm_group_label>Abemaciclib without Surgery</arm_group_label>
    <arm_group_label>Cohort 1 Surgery Arm</arm_group_label>
    <other_name>LY2835219</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Surgery</intervention_name>
    <description>Surgery</description>
    <arm_group_label>Abemaciclib with Surgery</arm_group_label>
    <arm_group_label>Cohort 1 Surgery Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be able to understand and willing to sign a written informed consent&#xD;
             document.&#xD;
&#xD;
          -  Participants must be able to adhere to the dosing and visit schedules, and agree to&#xD;
             record medication times accurately and consistently in a daily diary.&#xD;
&#xD;
          -  Participants must be at least 18 years old on day of signing informed consent.&#xD;
&#xD;
          -  Participants must have a Karnofsky Performance Status (KPS) ≥ 60&#xD;
&#xD;
          -  Participants must be able to swallow capsules/tablets&#xD;
&#xD;
          -  Participants with a prior or concurrent malignancy whose natural history or treatment&#xD;
             does not have the potential to interfere with the safety or efficacy of the trial are&#xD;
             eligible.&#xD;
&#xD;
        Nature of illness and treatment history&#xD;
&#xD;
          -  Participants must undergo central pathology review to histologically confirm the&#xD;
             diagnosis of glioblastoma, IDH-wildtype; glioblastoma variants; or astrocytoma,&#xD;
             IDH-mutant, WHO grade 4 (1 unstained slide or 1 H&amp;E slide must be submitted to and&#xD;
             reviewed by a pathologist at the DFCI Coordinating Center prior to enrollment of the&#xD;
             participant for central pathology review).&#xD;
&#xD;
          -  To be eligible for the study all participants (Cohort 1 and 2) are required to provide&#xD;
             genomic profiling data from assays performed in a CLIA-certified lab. A&#xD;
             sequencing-based assay is required and must include reporting of the RB1 gene in&#xD;
             explicit terms within the report. Only sequencing assays that include coverage of all&#xD;
             exons of the RB1 gene are able to be utilized (most commonly called a targeted exome&#xD;
             assay; e.g. Oncopanel, Impact, FoundationOne). In addition, patients must provide a&#xD;
             report of copy assessment which reports status of RB1. The reporting may be from a&#xD;
             copy array (ideally Oncoscan SNP array or Agilent array CGH) or can also be from&#xD;
             sequencing assay if copy status is explicitly provided with quantitative information&#xD;
             regarding the status of relevant genes. Specifically, the reporting should provide the&#xD;
             following information with respect to relevant biomarkers required for enrollment to&#xD;
             the study as listed below.&#xD;
&#xD;
          -  Results from genomic profiling must be sent to the DFCI Coordinating Center prior to&#xD;
             enrollment of the participant for central pathology review.&#xD;
&#xD;
               -  Inactivation of CDKN2A/B or C in the tumor by homozygous deletion (evidence for&#xD;
                  more than single copy loss for any of the genes defined as array CGH/SNP log2&#xD;
                  ratio of &lt;0.3 by array CGH; or from sequencing data with sufficient coverage for&#xD;
                  evaluation). Rearrangement/evidence or intragenic breaks by copy or sequencing&#xD;
                  assay also will be considered eligible for study (any copy status).&#xD;
&#xD;
               -  OR&#xD;
&#xD;
               -  CDK4 or CDK6 high-level amplification. (The amplicon size must be &lt;10Mb and the&#xD;
                  magnitude the gain must be log2 ratio &gt;1.5 or estimated as &gt;10 copies).&#xD;
&#xD;
               -  AND&#xD;
&#xD;
               -  Validation of wild-type RB status (no deletion/losses more than single copy by&#xD;
                  copy number or sequencing data; and/or no inactivating mutations by sequencing).&#xD;
&#xD;
          -  Participants must be at first relapse of GBM. Relapse is defined as progression&#xD;
             following initial therapy (i.e. radiation+/- chemo if that was used as initial&#xD;
             therapy). The intent therefore is that patients had no more than 1 prior therapy&#xD;
             (initial treatment). If the patient had a surgical resection for relapsed disease and&#xD;
             no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes&#xD;
             another surgical resection, this is considered to constitute 1 relapse.&#xD;
&#xD;
          -  Participants must have shown unequivocal evidence for tumor progression by MRI or CT&#xD;
             scan.&#xD;
&#xD;
               -  For Cohort 2 subjects, CT or MRI within 14 days prior to study registration. For&#xD;
                  Cohort 2, corticosteroid dose must be stable or decreasing for at least 5 days&#xD;
                  prior to the scan. If steroids are added or the steroid dose is increased between&#xD;
                  the date of the screening MRI or CT scan and the start of treatment, a new&#xD;
                  baseline MRI or CT is required.&#xD;
&#xD;
               -  For Cohort 1 subjects, CT or MRI should be performed ideally within 14 days prior&#xD;
                  to study registration, but because the screening MRI for this subset of subjects&#xD;
                  will not be used for evaluation of response, it is acceptable for this MRI/CT to&#xD;
                  have been performed greater than 14 days prior to registration if unavoidable.&#xD;
                  Furthermore, for this same reason, fluctuation in corticosteroid dose around this&#xD;
                  MRI does not warrant repeat scan so long as there is documented unequivocal&#xD;
                  evidence of tumor progression available.&#xD;
&#xD;
               -  For Cohort 1 subjects, there must be &gt; 2cm2 enhancing tissue available for&#xD;
                  resection and submission for study correlatives as determined by local treating&#xD;
                  team.&#xD;
&#xD;
          -  Confirmation of availability of sufficient tissue from a prior surgery for correlative&#xD;
             studies is required prior to enrollment; these samples must be sent to the DFCI&#xD;
             Coordinating Center within 60 days of registration. Cohort 1 participants must have&#xD;
             sufficient FFPE tissue from any surgery. Cohort 2 participants must have tissue from&#xD;
             biopsy or resection from the most recent recurrence surgery.&#xD;
&#xD;
          -  The following amount of archived tissue is required:&#xD;
&#xD;
               -  20 unstained formalin fixed paraffin embedded (FFPE) sections (standard 4-5&#xD;
                  micrometer thickness)&#xD;
&#xD;
               -  NOTE: if the above-mentioned tissue is not available from the most recent surgery&#xD;
                  revealing GBM, participants may be enrolled with tissue available from any prior&#xD;
                  surgery revealing GBM with prospective approval from the Overall PI.&#xD;
&#xD;
          -  An interval of at least 12 weeks from the completion of radiation therapy to start of&#xD;
             study drug unless there is a new area of enhancement consistent with recurrent tumor&#xD;
             outside the radiation field (defined as the region outside the high-dose region or 80%&#xD;
             isodose line) or there is unequivocal histologic confirmation of tumor progression.&#xD;
&#xD;
          -  Participants must have recovered to grade 0 or 1 or pre-treatment baseline from&#xD;
             clinically significant toxic effects of prior therapy (including but not limited to&#xD;
             exceptions of alopecia, laboratory values listed per inclusion criteria, and&#xD;
             lymphopenia which is common after therapy with temozolomide).&#xD;
&#xD;
          -  From the projected start of scheduled study treatment, the following time periods must&#xD;
             have elapsed:&#xD;
&#xD;
               -  4 weeks or 5 half-lives (whichever is shorter) from any investigational agent;&#xD;
&#xD;
               -  4 weeks from cytotoxic therapy (except 23 days for temozolomide; 6 weeks from&#xD;
                  nitrosoureas);&#xD;
&#xD;
               -  4 weeks from antibodies;&#xD;
&#xD;
               -  4 weeks or 5 half-lives (whichever is shorter) from other anti-tumor therapies.&#xD;
&#xD;
               -  2 days from Novo-TTF&#xD;
&#xD;
          -  Participants with prior therapy that included interstitial brachytherapy or&#xD;
             stereotactic radiosurgery must have confirmation of progressive disease based upon&#xD;
             nuclear imaging, MR spectroscopy, perfusion imaging or histopathology.&#xD;
&#xD;
          -  Participants having undergone recent resection or open biopsy or stereotactic biopsy&#xD;
             of recurrent or progressive tumor will be eligible for Cohort 2 as long as the&#xD;
             following conditions apply:&#xD;
&#xD;
               -  They have recovered from the effects of surgery.&#xD;
&#xD;
               -  Residual disease following resection of recurrent tumor is not mandated for&#xD;
                  eligibility. To best assess the extent of residual disease post-operatively, an&#xD;
                  MRI or CT scan should ideally have been performed no later than 96 hours&#xD;
                  following surgery, or at least 28 days post-operatively, but scans performed&#xD;
                  outside of this window are considered acceptable if no alternative is available.&#xD;
                  In either case, the baseline/screening MRI must be performed within 14 days prior&#xD;
                  to registration. If the participant is taking corticosteroids, the dose must be&#xD;
                  stable or decreasing for at least 5 days prior to the scan. If steroids are added&#xD;
                  or the steroid dose is increased between the date of the screening MRI or CT scan&#xD;
                  and the start of treatment, a new baseline MRI or CT is required.&#xD;
&#xD;
        Clinical labs - performed within 14 days prior to registration&#xD;
&#xD;
          -  Hematology:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1.5 x K/µL&#xD;
&#xD;
               -  Platelet count ≥ 100 x K/µL&#xD;
&#xD;
               -  Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
          -  Biochemistry:&#xD;
&#xD;
               -  Total serum calcium (corrected for serum albumin as needed) or ionized calcium&#xD;
                  within institution's normal range.&#xD;
&#xD;
               -  Magnesium within institution's normal range.&#xD;
&#xD;
               -  AST (SGOT) and ALT (SGPT) ≤ 3.0 x institution's ULN&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 x institution's ULN&#xD;
&#xD;
               -  Serum creatinine ≤ 1.5 x institution's ULN or calculated 24-hour creatinine&#xD;
                  clearance ≥ 50 mL/min&#xD;
&#xD;
               -  Serum amylase ≤ 1.5 x institution's ULN&#xD;
&#xD;
               -  Serum lipase ≤ 1.5 x institution's ULN&#xD;
&#xD;
          -  Coagulation studies:&#xD;
&#xD;
               -  INR &lt; 2.0&#xD;
&#xD;
               -  PTT ≤ institution's ULN, unless receiving therapeutic low molecular weight&#xD;
                  heparin or oral factor Xa inhibitors Pregnancy and Reproduction&#xD;
&#xD;
          -  The effects of abemaciclib on the developing human fetus are unknown. For this reason,&#xD;
             women of child-bearing potential (WOCBP) must agree to use a medically approved&#xD;
             contraceptive method during the treatment period and for 3 months following the last&#xD;
             dose of abemaciclib. Men must agree to use a reliable method of birth control and to&#xD;
             not donate sperm during the study and for at least 3 months following the last dose of&#xD;
             abemaciclib. Contraceptive methods may include an intrauterine device [IUD] or barrier&#xD;
             method. If condoms are used as a barrier method, a spermicidal agent should be added&#xD;
             as a double barrier protection.&#xD;
&#xD;
          -  NOTE: Women are considered post-menopausal and not of child bearing potential if they&#xD;
             have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical&#xD;
             profile (e.g., age appropriate, history of vasomotor symptoms) or six months of&#xD;
             spontaneous amenorrhea with serum FSH levels &gt; 40 mIU/mL and estradiol &lt; 20 pg/mL or&#xD;
             have had surgical bilateral oophorectomy (with or without hysterectomy) at least six&#xD;
             weeks ago. In the case of oophorectomy alone, only when the reproductive status of the&#xD;
             woman has been confirmed by follow up hormone level assessment is she considered not&#xD;
             of child bearing potential.&#xD;
&#xD;
          -  Women of child-bearing potential must have a negative serum pregnancy test within 7&#xD;
             days prior to first dose of abemaciclib .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Pathology&#xD;
&#xD;
          -  Prior evidence of 1p/19q co-deletion.&#xD;
&#xD;
          -  IDH1/2 mutation in any prior biopsy.&#xD;
&#xD;
        Previous therapies&#xD;
&#xD;
          -  Participants who have received prior treatment with a CDK4/6 inhibitor.&#xD;
&#xD;
          -  Participants who have received anti-VEGF targeted agents (e.g. bevacizumab, cediranib,&#xD;
             aflibercept, vandetanib, XL184, sunitinib etc).&#xD;
&#xD;
        Concomitant medications&#xD;
&#xD;
          -  Participants taking an enzyme-inducing anti-epileptic drug (EIAED): phenobarbital,&#xD;
             phenytoin, fosphenytoin, primidone, carbamazepine, oxcarbazepine, eslicarbazepine,&#xD;
             rufinamide, and felbamate. Participants must be off any EIAEDs for at least 14 days&#xD;
             prior to starting study drug. A list of EIAEDs and other inducers of CYP3A4 can be&#xD;
             found.&#xD;
&#xD;
          -  Participants taking a drug known to be a strong inhibitor or inducer of isoenzyme&#xD;
             CYP3A . Participant must be off CYP3A inhibitors and inducers for at least 14 days&#xD;
             prior to starting study drug. NOTE: participants must avoid consumption of Seville&#xD;
             oranges (and juice), grapefruits or grapefruit juice, grapefruit hybrids, pummelos and&#xD;
             exotic citrus fruits from 7 days prior to the first dose of study drug and during the&#xD;
             entire study treatment period due to potential CYP3A4 interaction.&#xD;
&#xD;
          -  Participants receiving any other investigational agents.&#xD;
&#xD;
          -  Current use of herbal preparations/medications, including but not limited to: St.&#xD;
             John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA),&#xD;
             yohimbe, saw palmetto, ginseng. Participants should stop using these herbal&#xD;
             medications 7 days prior to first dose of study drug.&#xD;
&#xD;
          -  Current use of warfarin sodium or any other coumadin-derivative anticoagulant.&#xD;
             Participants must be off Coumadin-derivative anticoagulants for at least 7 days prior&#xD;
             to starting study drug. Low molecular weight heparin is allowed.&#xD;
&#xD;
          -  Requires treatment with high dose systemic corticosteroids defined as dexamethasone &gt;&#xD;
             4 mg/day or bioequivalent for at least 3 consecutive days within 2 weeks of&#xD;
             registration.&#xD;
&#xD;
        Other illnesses&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to abemaciclib.&#xD;
&#xD;
          -  History of intratumoral or peritumoral hemorrhage if deemed significant by the&#xD;
             treating investigator. If there are questions, the treating investigator should&#xD;
             contact the study Overall P.I., Eudocia Quant Lee, MD, at 617-632-2166 or&#xD;
             eqlee@partners.org.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, chronic liver disease (e.g., cirrhosis, hepatitis), chronic renal disease,&#xD;
             pancreatitis, chronic pulmonary disease, or psychiatric illness/social situations that&#xD;
             would limit compliance with study requirements. Subjects must be free of any&#xD;
             clinically relevant disease (other than glioma) that would, in the treating&#xD;
             investigator's opinion, interfere with the conduct of the study or study evaluations.&#xD;
&#xD;
          -  Participant has an active systemic fungal and/or known viral infection (for example,&#xD;
             human immunodeficiency virus antibodies, hepatitis B surface antigen or hepatitis C&#xD;
             antibodies).&#xD;
&#xD;
          -  Participants with diarrhea ≥ CTCAE grade 2&#xD;
&#xD;
          -  Participant has active cardiac disease including any of the following:&#xD;
&#xD;
               -  Angina pectoris that requires the use of anti-anginal medications&#xD;
&#xD;
               -  Ventricular arrhythmias except for benign premature ventricular contractions&#xD;
&#xD;
               -  Supraventricular and nodal arrythmias requiring a pacemaker or not controlled&#xD;
                  with medication&#xD;
&#xD;
               -  Conduction abnormality requiring a pacemaker&#xD;
&#xD;
               -  Valvular disease with document compromise in cardiac function&#xD;
&#xD;
               -  Symptomatic pericarditis&#xD;
&#xD;
          -  Participant has a history of cardiac dysfunction including any of the following:&#xD;
&#xD;
               -  Myocardial infarction within the last 6 months prior to start of study drug,&#xD;
                  documents by persistent elevated cardiac enzymes or persistent regional wall&#xD;
                  abnormalities on assessment of LVEF function&#xD;
&#xD;
               -  History of documented congestive heart failure (New York Heart Association&#xD;
                  functional classification III-IV, see Appendix B)&#xD;
&#xD;
               -  Documented cardiomyopathy&#xD;
&#xD;
               -  Congenital long QT syndrome&#xD;
&#xD;
          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly&#xD;
             alter the absorption of abemaciclib (e.g., ulcerative diseases, uncontrolled nausea,&#xD;
             vomiting, diarrhea, malabsorption syndrome, or extensive small bowel resection).&#xD;
             Participants with unresolved diarrhea ≥ CTCAE grade 2 will be excluded as previously&#xD;
             indicated.&#xD;
&#xD;
          -  Participants who have undergone major systemic surgery ≤ 2 weeks prior to starting&#xD;
             study drug or who have not recovered from side effects of such therapy.&#xD;
&#xD;
          -  Participants who are pregnant or breastfeeding.&#xD;
&#xD;
          -  Participants with history of known coagulopathy that increases risk of bleeding or a&#xD;
             history of clinically significant hemorrhage within 12 months of start 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>
  <overall_official>
    <last_name>Eudocia Q Lee, MD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber Cancer Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143-0372</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan-Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UT, M.D. Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>October 7, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Dana-Farber Cancer Institute</investigator_affiliation>
    <investigator_full_name>Eudocia Quant Lee, MD</investigator_full_name>
    <investigator_title>MD, MPH</investigator_title>
  </responsible_party>
  <keyword>Brain Tumor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02981940
org study id: 16-383
nct id: NCT02981940
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This research study is studying a targeted therapy as a possible treatment for recurrent
      glioblastoma (GBM).

      The following intervention will be used in this study:

      -Abemaciclib
This research study is a Phase 0/II clinical trial. Phase 0 clinical trials use only a few
      small doses of a drug. Phase II clinical trials test the safety and effectiveness of an
      investigational drug to learn whether the drug works in treating a specific disease.
      "Investigational" means that the drug is being studied.

      The FDA (the U.S. Food and Drug Administration) has not approved abemaciclib as a treatment
      for any disease.

      Many brain cancers show over expression of a protein called cyclin D1. That means that the
      body makes too much cyclin D1, which affects enzymes called CDK 4 and CDK 6. Enzymes are
      substances in the body that help reactions between cells happen. Too much cyclin D1 triggers
      CDK 4 and CDK 6 to make more cells than normal. This extra cell production leads to the
      growth of tumors.

      In laboratory studies, Abemaciclib was able to enter the brain, stop CDK 4 and CDK 6 from
      making cells, and slow growth of mice Glioblastoma.

      In this research study, the investigators are looking to see how safe and effect Abemaciclib
      is with the participant type of cancer. In the surgical participants, the investigators are
      looking to see if Abemaciclib reached the brain tumor.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Intratumoral abemaciclib concentration
time frame: 2 years
measure: 6-Month Progression Free Survival (PFS6)
time frame: 6 months
measure: pRB expression level of tumor tissue
time frame: 2 years
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 2 years
description: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
measure: Area under the plasma concentration versus time curve (AUC)
time frame: 4 months
description: PK measurements expressed as Area under the plasma concentration versus time curve (AUC) of Abemaciclib [Time Frame C1D1 (pre-treatment), C2D1, C3D1 and C4D1 (each cycle is 28 days)].
measure: Peak Plasma Concentration (Cmax)
time frame: 4 months
description: PK measurements expressed as Peak Plasma Concentration (Cmax) of Abemaciclib [Time Frame C1D1 (pre-treatment), C2D1, C3D1 and C4D1 (each cycle is 28 days)]
measure: Radiographic Response Rate
time frame: 2 years
measure: Median Progression Free Survival
time frame: 2 years
measure: Overall Survival
time frame: 2 years
arm group label: Abemaciclib with Surgery
arm group type: Experimental
description: Abemaciclib will be administered on a continuous twice daily dosing schedule
Patients who require re-operation will receive a short preoperative course of Abemaciclib
Tissue will be used to investigate the ability of Abemaciclib to pass through the blood brain barrier.
After recovery from surgery, participants will resume Abemaciclib. Each cycle lasts 28 days.
NOTE: enrollment to this arm is complete
arm group label: Abemaciclib without Surgery
arm group type: Experimental
description: Abemaciclib will be administered on a continuous twice daily dosing schedule. Each Cycle last 28 days.
NOTE: enrollment to this arm is complete
arm group label: Cohort 1 Surgery Arm
arm group type: Experimental
description: Participants who require reoperation will be treated with abemaciclib for 10-14 days prior to surgery. Tissue will be used to further investigate the abilities of Abemaciclib. After surgery participants will come off study and pursue standard of care treatments at their treating physician's discretion.
intervention type: Drug
intervention name: Abemaciclib
description: Abemaciclib capsule
arm group label: Abemaciclib with Surgery
arm group label: Abemaciclib without Surgery
arm group label: Cohort 1 Surgery Arm
other name: LY2835219
intervention type: Procedure
intervention name: Surgery
description: Surgery
arm group label: Abemaciclib with Surgery
arm group label: Cohort 1 Surgery Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eudocia Q Lee, MD MPH
role: Principal Investigator
affiliation: Dana-Farber Cancer Institute
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Dana-Farber Cancer Institute
investigator full name: Eudocia Quant Lee, MD
investigator title: MD, MPH
mesh term: Glioblastoma
sharing ipd: No