<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/NCT04469764</url>
  </required_header>
  <id_info>
    <org_study_id>20-000769</org_study_id>
    <secondary_id>NCI-2020-04544</secondary_id>
    <nct_id>NCT04469764</nct_id>
  </id_info>
  <brief_title>Abemaciclib for the Treatment of Recurrent Ovarian or Endometrial Cancer</brief_title>
  <official_title>An Open Label Phase II Study of the Efficacy and Safety of Abemaciclib, a Cyclin Dependent Kinase (CDK4/6) Inhibitor in Selected Patients With Recurrent Ovarian or Endometrial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jonsson Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eli Lilly and Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Jonsson Comprehensive Cancer Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well abemaciclib works in treating patients with ovarian or&#xD;
      endometrial cancer that has an activation of the CDK4/6 pathway and that has come back&#xD;
      (recurrent). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes&#xD;
      needed for cell growth. Giving abemaciclib may work better for the treatment of recurrent&#xD;
      ovarian and endometrial cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To obtain an estimate of the proportion of patients' progression-free at 16 weeks (16 week&#xD;
      progression free survival [PFS] rate) in patients with recurrent ovarian (including fallopian&#xD;
      tube and primary peritoneal) or recurrent endometrial cancer following treatment with&#xD;
      abemaciclib as a molecularly matched targeted therapy.&#xD;
&#xD;
      SECONDARY OBJECTIVE:&#xD;
&#xD;
      I. To assess objective response rate (ORR) as per Response Evaluation Criteria in Solid&#xD;
      Tumors (RECIST), progression free survival (PFS) and safety following treatment with&#xD;
      abemaciclib as a molecularly matched targeted therapy.&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. To explore the relationship between response to abemaciclib and somatic gene alterations&#xD;
      that lead to CDK4/6 activation in ovarian cancer.&#xD;
&#xD;
      II. To explore the relationship between response to abemaciclib and hormone receptor&#xD;
      expression levels as well as somatic gene alterations that lead to CDK4/6 activation in&#xD;
      endometrial cancer.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Patients with tumors&#xD;
      that are hormone receptor positive also receive anastrozole or letrozole per standard of&#xD;
      care. Cycles repeat every 28 days in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 30 days, and then every 12&#xD;
      weeks up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 16, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">July 1, 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients who are progression-free</measure>
    <time_frame>At 16 weeks</time_frame>
    <description>Will be calculated with corresponding 95% unadjusted exact binomial confidence interval (CI).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Assessed per Response Evaluation Criteria in Solid Tumors (RECIST).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS)</measure>
    <time_frame>Time from registration until date of progression or death, assessed up to 1 year</time_frame>
    <description>Date of progression will be defined as the date of the first imaging or clinical exam or biochemical occurrence showing disease progression. PFS will be calculated with corresponding 95% unadjusted exact binomial confidence interval. Kaplan-Meier estimates and Kaplan Meier plots of this endpoint will be produced. Two-sided 95% confidence intervals will accompany the Kaplan-Meier estimate of the median.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>At 16 weeks and up to 90 days after completion of treatment</time_frame>
    <description>To assess safety</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical benefit rate</measure>
    <time_frame>Up to 1 year after completion of treatment</time_frame>
    <description>Defined as achieving a confirmed objective response (complete response [CR] or partial response [PR]) or achieving stable disease for a minimum duration of 4 months, will be provided with the exact two-sided 95% confidence interval.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">32</enrollment>
  <condition>Recurrent Endometrial Carcinoma</condition>
  <condition>Recurrent Fallopian Tube Carcinoma</condition>
  <condition>Recurrent Ovarian Carcinoma</condition>
  <condition>Recurrent Primary Peritoneal Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (abemaciclib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive abemaciclib PO BID on days 1-28. Patients with tumors that are hormone receptor positive also receive and anastrozole or letrozole per standard of care. 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>Abemaciclib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (abemaciclib)</arm_group_label>
    <other_name>LY-2835219</other_name>
    <other_name>LY2835219</other_name>
    <other_name>Verzenio</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anastrozole</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (abemaciclib)</arm_group_label>
    <other_name>Anastrazole</other_name>
    <other_name>Arimidex</other_name>
    <other_name>ICI D1033</other_name>
    <other_name>ICI-D1033</other_name>
    <other_name>ZD-1033</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Letrozole</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (abemaciclib)</arm_group_label>
    <other_name>CGS 20267</other_name>
    <other_name>Femara</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically-confirmed ovarian epithelial (including fallopian tube and primary&#xD;
             peritoneal) cancer or endometrial cancer&#xD;
&#xD;
          -  Molecular tumor board confirms that patient's archival ovarian cancer tumor specimen&#xD;
             has been assessed using standard of care genomic profiling and demonstrates CDK4/6&#xD;
             activation features&#xD;
&#xD;
          -  Molecular tumor board confirms that patient's archival endometrial cancer tumor&#xD;
             specimen has been assessed using standard of care genomic profiling and is of&#xD;
             endometrioid histology, has positive hormone receptor expression and lack of Cyclin E&#xD;
             gene (CCNE) amplification or retinoblastoma susceptibility gene product (RB) loss&#xD;
&#xD;
          -  At least one prior chemotherapy regimen for the treatment of recurrent ovarian or&#xD;
             endometrial cancer&#xD;
&#xD;
          -  Patients who received chemotherapy must have recovered (Common Terminology Criteria&#xD;
             for Adverse Events [CTCAE] grade =&lt; 1) from the acute effects of chemotherapy except&#xD;
             for residual alopecia or grade 2 peripheral neuropathy prior to enrollment. A washout&#xD;
             period of at least 21 days is required between last chemotherapy dose and study&#xD;
             initiation&#xD;
&#xD;
          -  Patients who received radiotherapy must have completed and fully recovered from the&#xD;
             acute effects of radiotherapy. A washout period of at least 14 days is required&#xD;
             between end of radiotherapy and study initiation&#xD;
&#xD;
          -  The patient is able to swallow oral medications&#xD;
&#xD;
          -  Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2&#xD;
&#xD;
          -  Patient must be willing and able to comply with scheduled visits, treatment plans,&#xD;
             laboratory tests, and other study procedures&#xD;
&#xD;
          -  Informed consent must be obtained in writing for all patients prior to performing&#xD;
             study/screening procedures and prior to registration into the study&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1.5 x 10^9/L&#xD;
&#xD;
          -  Platelets &gt;= 100 x 10^9/L&#xD;
&#xD;
          -  Hemoglobin &gt;= 8 g/dL. Patients may receive erythrocyte transfusions to achieve this&#xD;
             hemoglobin level at the discretion of the investigator. Initial treatment must not&#xD;
             begin earlier than the day after the erythrocyte transfusion&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x upper limit of normal (ULN). Patients with Gilbert's syndrome&#xD;
             with a total bilirubin =&lt; 2.0 times ULN and direct bilirubin within normal limits are&#xD;
             permitted&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x ULN&#xD;
&#xD;
          -  Female participants of childbearing potential must have a negative serum pregnancy&#xD;
             test within 7 days of the first dose of abemaciclib and agree to use a highly&#xD;
             effective contraception method during the treatment period and for 3 weeks following&#xD;
             the last dose of abemaciclib&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Anticipation of immediate need for a major surgical procedure (e.g., impending bowel&#xD;
             obstruction, gastrointestinal perforation) or radiation therapy during the trial&#xD;
&#xD;
          -  Diagnosis of any second malignancy within the last 5 years, except for adequately&#xD;
             treated basal cell or squamous cell skin cancer, or for in situ carcinoma of the&#xD;
             cervix uteri or breast&#xD;
&#xD;
          -  Treatment with chemotherapy, surgery, blood products, or an investigational agent&#xD;
             within 3 weeks of trial enrollment&#xD;
&#xD;
          -  Any of the following within 6 months prior to trial registration: myocardial&#xD;
             infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft,&#xD;
             New York Heart Association (NYHA) class III or IV congestive heart failure,&#xD;
             cerebrovascular accident or transient ischemic attack, pulmonary embolism&#xD;
&#xD;
          -  Unstable brain metastases or carcinomatous meningitis&#xD;
&#xD;
          -  Patient of child-bearing potential is evidently pregnant or is breast feeding. A woman&#xD;
             with child bearing potential is defined as not surgically sterile or being&#xD;
             post-menopausal for less than 6 months&#xD;
&#xD;
          -  Patient of child-bearing potential is not willing to use adequate contraceptive&#xD;
             precautions. Adequate effective method of contraception are those which result in low&#xD;
             failure rates, less than 1% per year, such as non-hormonal intrauterine device (IUD),&#xD;
             condoms, sexual abstinence or vasectomized partner&#xD;
&#xD;
          -  The patient has serious preexisting medical condition(s) that would preclude&#xD;
             participation in this study (for example, interstitial lung disease, severe dyspnea at&#xD;
             rest or requiring oxygen therapy, history of major surgical resection involving the&#xD;
             stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a&#xD;
             preexisting chronic condition resulting in baseline grade 2 or higher diarrhea)&#xD;
&#xD;
          -  The patient has active bacterial infection (requiring intravenous [IV] antibiotics at&#xD;
             time of initiating study treatment), fungal infection, or detectable viral infection&#xD;
             (such as known human immunodeficiency virus positivity or with known active hepatitis&#xD;
             B or C [for example, hepatitis B surface antigen positive]. Screening is not required&#xD;
             for enrollment&#xD;
&#xD;
          -  The patient has a personal history of any of the following conditions: syncope of&#xD;
             cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but&#xD;
             not limited to, ventricular tachycardia and ventricular fibrillation), or sudden&#xD;
             cardiac arrest&#xD;
&#xD;
          -  Current use or anticipated need for: Food or drugs that are known strong CYP3A4&#xD;
             inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole,&#xD;
             posaconazole, erythromycin, clarithromycin, tilithromycin, indinavir, saquinavir,&#xD;
             ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone,&#xD;
             diltiazem, and delaviridine)&#xD;
&#xD;
          -  Other severe acute or chronic medical or psychiatric condition, or significant&#xD;
             laboratory abnormality requiring further investigation that may cause undue risk for&#xD;
             the patient's safety, inhibit protocol participation, or interfere with interpretation&#xD;
             of trial results, and in the judgment of the investigator would make the patient&#xD;
             inappropriate for entry into this trial&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gottfried E Konecny</last_name>
    <role>Principal Investigator</role>
    <affiliation>UCLA / Jonsson Comprehensive Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gina A Khachatrian</last_name>
    <phone>310 825-7028</phone>
    <email>gkhachatrian@mednet.ucla.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Kimberly Kelly</last_name>
    <phone>310-794-5517</phone>
    <email>kmkelly@mednet.ucla.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>UCLA / Jonsson Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kim Kelly</last_name>
      <phone>310-206-8309</phone>
      <email>kmkelly@mednet.ucla.edu</email>
    </contact>
    <investigator>
      <last_name>Gottfried E. Konecny</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <last_update_submitted>June 5, 2023</last_update_submitted>
  <last_update_submitted_qc>June 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 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>Carcinoma</mesh_term>
    <mesh_term>Endometrial Neoplasms</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Letrozole</mesh_term>
    <mesh_term>Anastrozole</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/NCT04469764
org study id: 20-000769
secondary id: NCI-2020-04544
nct id: NCT04469764
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase II trial studies how well abemaciclib works in treating patients with ovarian or
      endometrial cancer that has an activation of the CDK4/6 pathway and that has come back
      (recurrent). Abemaciclib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Giving abemaciclib may work better for the treatment of recurrent
      ovarian and endometrial cancer.
PRIMARY OBJECTIVE:

      I. To obtain an estimate of the proportion of patients' progression-free at 16 weeks (16 week
      progression free survival [PFS] rate) in patients with recurrent ovarian (including fallopian
      tube and primary peritoneal) or recurrent endometrial cancer following treatment with
      abemaciclib as a molecularly matched targeted therapy.

      SECONDARY OBJECTIVE:

      I. To assess objective response rate (ORR) as per Response Evaluation Criteria in Solid
      Tumors (RECIST), progression free survival (PFS) and safety following treatment with
      abemaciclib as a molecularly matched targeted therapy.

      EXPLORATORY OBJECTIVES:

      I. To explore the relationship between response to abemaciclib and somatic gene alterations
      that lead to CDK4/6 activation in ovarian cancer.

      II. To explore the relationship between response to abemaciclib and hormone receptor
      expression levels as well as somatic gene alterations that lead to CDK4/6 activation in
      endometrial cancer.

      OUTLINE:

      Patients receive abemaciclib orally (PO) twice daily (BID) on days 1-28. Patients with tumors
      that are hormone receptor positive also receive anastrozole or letrozole per standard of
      care. Cycles repeat every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up for 30 days, and then every 12
      weeks up to 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients who are progression-free
time frame: At 16 weeks
description: Will be calculated with corresponding 95% unadjusted exact binomial confidence interval (CI).
measure: Objective response rate (ORR)
time frame: Up to 1 year
description: Assessed per Response Evaluation Criteria in Solid Tumors (RECIST).
measure: Progression free survival (PFS)
time frame: Time from registration until date of progression or death, assessed up to 1 year
description: Date of progression will be defined as the date of the first imaging or clinical exam or biochemical occurrence showing disease progression. PFS will be calculated with corresponding 95% unadjusted exact binomial confidence interval. Kaplan-Meier estimates and Kaplan Meier plots of this endpoint will be produced. Two-sided 95% confidence intervals will accompany the Kaplan-Meier estimate of the median.
measure: Incidence of adverse events
time frame: At 16 weeks and up to 90 days after completion of treatment
description: To assess safety
measure: Clinical benefit rate
time frame: Up to 1 year after completion of treatment
description: Defined as achieving a confirmed objective response (complete response [CR] or partial response [PR]) or achieving stable disease for a minimum duration of 4 months, will be provided with the exact two-sided 95% confidence interval.
arm group label: Treatment (abemaciclib)
arm group type: Experimental
description: Patients receive abemaciclib PO BID on days 1-28. Patients with tumors that are hormone receptor positive also receive and anastrozole or letrozole per standard of care. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Abemaciclib
description: Given PO
arm group label: Treatment (abemaciclib)
other name: LY-2835219
other name: LY2835219
other name: Verzenio
intervention type: Drug
intervention name: Anastrozole
description: Given PO
arm group label: Treatment (abemaciclib)
other name: Anastrazole
other name: Arimidex
other name: ICI D1033
other name: ICI-D1033
other name: ZD-1033
intervention type: Drug
intervention name: Letrozole
description: Given PO
arm group label: Treatment (abemaciclib)
other name: CGS 20267
other name: Femara
criteria: 
gender: Female
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Gottfried E Konecny
role: Principal Investigator
affiliation: UCLA / Jonsson Comprehensive Cancer Center
last name: Gina A Khachatrian
phone: 310 825-7028
email: gkhachatrian@mednet.ucla.edu
last name: Kimberly Kelly
phone: 310-794-5517
email: kmkelly@mednet.ucla.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Endometrial Neoplasms
mesh term: Recurrence
mesh term: Letrozole
mesh term: Anastrozole