<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/NCT03253679</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-01498</org_study_id>
    <secondary_id>NCI-2017-01498</secondary_id>
    <secondary_id>NCI10136</secondary_id>
    <secondary_id>10136</secondary_id>
    <secondary_id>10136</secondary_id>
    <secondary_id>UM1CA186688</secondary_id>
    <nct_id>NCT03253679</nct_id>
  </id_info>
  <brief_title>AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification</brief_title>
  <official_title>A Phase 2 Study of AZD1775, a Wee1 Inhibitor, in Patients With CCNE1 Amplification</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</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 II trial studies how well AZD1775 works in treating patients with solid tumors&#xD;
      with CCNE1 amplification that have spread to other places in the body (advanced) and do not&#xD;
      respond to treatment (refractory). AZD1775 may stop the growth of tumor cells by blocking&#xD;
      some of the enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the proportion of patients with the objective response rate (ORR) to&#xD;
      adavosertib (AZD1775) in patients with advanced refractory cancers with CCNE1 amplification.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment&#xD;
      with AZD1775 in patients with advanced refractory cancers with CCNE1 amplification.&#xD;
&#xD;
      II. To evaluate proportion of patients with extended time to progression (time to progression&#xD;
      on AZD1775/ time to progression on last line of therapy &gt;= 1.3).&#xD;
&#xD;
      III. To evaluate time until death or disease progression. IV. To identify potential&#xD;
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or&#xD;
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and&#xD;
      imaging-based assessment platforms.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat&#xD;
      every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up for 4 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 24, 2018</start_date>
  <completion_date type="Actual">October 31, 2022</completion_date>
  <primary_completion_date type="Actual">October 31, 2022</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>Objective Response Rate (ORR)</measure>
    <time_frame>Up to 2 years 6 months</time_frame>
    <description>ORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To Evaluate the Proportion of Patients Alive and Progression Free of Treatment With AZD1775 in Patients With Advanced Refractory Cancers With CCNE1 Amplification.</measure>
    <time_frame>Up to 2 years 6 months</time_frame>
    <description>Estimated using the Kaplan-Meier Method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To Evaluate Time Until Death or Disease Progression.</measure>
    <time_frame>Up to 2 years 6 months</time_frame>
    <description>Estimated using the Kaplan-Meier Method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Responses</measure>
    <time_frame>Up to 2 years 6 months</time_frame>
    <description>(time to progression on AZD1775/ time to progression on last line of therapy &gt;= 1.3).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.</measure>
    <time_frame>Up to 2 years 6 months</time_frame>
    <description>Immunohistochemistry, reverse phase protein arrays, and next generation sequencing for targeted exome panel are used to reveal potential biomarkers predicting major clinical outcomes, and potential mechanisms of acquired resistance by comparing molecular signatures at baseline versus at time of relapse in responders.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <arm_group>
    <arm_group_label>Treatment (adavosertib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Adavosertib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (adavosertib)</arm_group_label>
    <other_name>AZD-1775</other_name>
    <other_name>AZD1775</other_name>
    <other_name>MK-1775</other_name>
    <other_name>MK1775</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have one of the histologically advanced solid tumors harboring CCNE1&#xD;
             amplification: Their diseases are refractory to, or do not have, standard-of-care&#xD;
             therapy; or they declined standard-of-care therapy; CCNE1 amplification is defined in&#xD;
             a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory: CCNE1&#xD;
             amplification &gt; 7 based on targeted custom Ampliseq panel on the Ion Torrent Personal&#xD;
             Genoma Machine (PGM); or CCNE1 amplification on alternate CLIA platforms such as&#xD;
             Foundation One, University of Washington (UW)-OncoPlex-Cancer Gene Panel, Memorial&#xD;
             Sloan Kettering (MSK)-Integrated Mutation Profiling of Actionable Cancer Targets&#xD;
             (IMPACT), Solid Tumor Genomic Assay (Life Technologies), etc. will also be eligible to&#xD;
             be treated after principal investigator (PI) approval; patients with known CCNE1&#xD;
             amplification on local or commercial platforms can start treatment after planned&#xD;
             biopsy or submission of recent archival sample; central next generation sequencing&#xD;
             (NGS) CCNE1 and fluorescence in-situ hybridization (FISH) testing will be performed to&#xD;
             confirm the result&#xD;
&#xD;
          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version&#xD;
             1.1&#xD;
&#xD;
          -  Has read and understands the informed consent form (ICF) and has given written ICF&#xD;
             prior to any study procedures; patients with impaired decision making capacity (IDMC)&#xD;
             must have a close caregiver or legally authorized representative (LAR)&#xD;
&#xD;
          -  Any prior radiation must have been completed at least 7 days prior to the start of&#xD;
             study drugs, and patients must have recovered from any acute adverse effects prior to&#xD;
             the start of study treatment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1500/uL (within 14 days of study drug[s]&#xD;
             initiation)&#xD;
&#xD;
          -  Hemoglobin (HgB) &gt;= 9 g/dL for mono-therapy (within 14 days of study drug[s]&#xD;
             initiation)&#xD;
&#xD;
          -  Platelets &gt;= 100,000/uL (within 14 days of study drug[s] initiation)&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =&lt; 3 x upper limit&#xD;
             of normal (ULN) or =&lt; 5 x ULN if known hepatic metastases (within 14 days of study&#xD;
             drug[s] initiation)&#xD;
&#xD;
          -  Serum bilirubin &lt; ULN or &lt; 1.5 x ULN in patients with liver metastases; or total&#xD;
             bilirubin &lt; 3.0 x ULN with direct bilirubin within normal limits (WNL) in patients&#xD;
             with well documented Gilbert's syndrome (within 14 days of study drug[s] initiation)&#xD;
&#xD;
          -  Serum creatinine =&lt; 1.5 x ULN, or calculated creatinine clearance (CrCl) &gt;= 45 mL/min&#xD;
             as calculated by the Cockcroft-Gault method or 24-hour measured urine CrCl &gt;= 45&#xD;
             mL/min (within 14 days of study drug[s] initiation)&#xD;
&#xD;
          -  Female patients who are not of child-bearing potential and fertile females of&#xD;
             childbearing potential who agree to use adequate contraceptive measures from 2 weeks&#xD;
             prior to the study and until 1 month after study treatment discontinuation, who are&#xD;
             not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days&#xD;
             prior to the start of study treatment; male patients willing to abstain or use barrier&#xD;
             contraception (i.e. condoms) for the duration of the study and for 3 months after&#xD;
             treatment stops&#xD;
&#xD;
          -  Willingness and ability to comply with study and follow-up procedures&#xD;
&#xD;
          -  Ability to take oral medications without medical history of malabsorption or other&#xD;
             chronic gastrointestinal disease, or other conditions that may hamper compliance&#xD;
             and/or absorption of the study agent&#xD;
&#xD;
          -  No prior treatment with wee1 kinase inhibition&#xD;
&#xD;
          -  Provision of an archival tissue block, or 10 formalin-fixed paraffin-embedded (FFPE)&#xD;
             slides, if available, and if not available having biopsiable disease and agreeing to&#xD;
             pre-treatment biopsies&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of anti-cancer treatment drug =&lt; 21 days or 5 half-lives (whichever is shorter)&#xD;
             prior to the first dose of AZD1775; for drugs for which 5 half-lives is =&lt; 21 days, a&#xD;
             minimum of 10 days between termination of the prior treatment and administration of&#xD;
             AZD1775 treatment is required&#xD;
&#xD;
          -  Previous radiation therapy completed =&lt; 7 days prior to the start of study drugs&#xD;
&#xD;
          -  Major surgical procedures =&lt; 28 days of beginning AZD1775, or minor surgical&#xD;
             procedures =&lt; 7 days; no waiting period required following port-a-cath or other&#xD;
             central venous access placement&#xD;
&#xD;
          -  Unresolved grade 2 toxicity from prior therapy (except alopecia or anorexia)&#xD;
&#xD;
          -  Patient has an inability to swallow oral medications; Note: Patient may not have a&#xD;
             percutaneous endoscopic gastrostomy (PEG) tube or be receiving total parenteral&#xD;
             nutrition (TPN)&#xD;
&#xD;
          -  No other anticancer-therapy (chemotherapy, immunotherapy, hormonal anti-cancer&#xD;
             therapy, radiotherapy [except for palliative local radiotherapy]), biological therapy&#xD;
             or other novel agent is to be permitted while the patient is receiving study&#xD;
             medication; patients on luteinizing hormone-releasing hormone (LHRH) analogue&#xD;
             treatment for more than 6 months are allowed entry into the study and may continue at&#xD;
             the discretion of the investigator&#xD;
&#xD;
          -  Known malignant central nervous system (CNS) disease other than neurologically stable,&#xD;
             treated brain metastases - defined as metastasis having no evidence of progression or&#xD;
             hemorrhage for at least 2 weeks after treatment; must be off any systemic&#xD;
             corticosteroids for the treatment of brain metastases for at least 14 days prior to&#xD;
             enrolment&#xD;
&#xD;
          -  Patient has had prescription or non-prescription drugs or other products known to be&#xD;
             sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index,&#xD;
             or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued&#xD;
             2 weeks prior to day 1 of dosing and withheld throughout the study until 2 weeks after&#xD;
             the last dose of study drug; co-administration of aprepitant or fosaprepitant during&#xD;
             this study is prohibited; the use of sensitive substrates of CYP3A4, such as&#xD;
             atorvastatin, simvastatin and lovastatin, is also prohibited in this study&#xD;
&#xD;
          -  Herbal preparations are not allowed throughout the study; these herbal medications&#xD;
             include but are not limited to: St. John's wort, kava, ephedra (ma hung), gingko&#xD;
             biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto and ginseng; patients&#xD;
             should stop using these herbal medications 7 days prior to first dose of study&#xD;
             treatment&#xD;
&#xD;
          -  Any known hypersensitivity or contraindication to the components of the study drug&#xD;
             AZD1775&#xD;
&#xD;
          -  Any of the following cardiac diseases currently or within the last 6 months as defined&#xD;
             by New York Heart Association (NYHA) &gt;= class 2&#xD;
&#xD;
               -  Unstable angina pectoris&#xD;
&#xD;
               -  Congestive heart failure&#xD;
&#xD;
               -  Acute myocardial infarction&#xD;
&#xD;
               -  Conduction abnormality not controlled with pacemaker or medication&#xD;
&#xD;
               -  Significant ventricular or supraventricular arrhythmias (patients with chronic&#xD;
                  rate-controlled atrial fibrillation in the absence of other cardiac abnormalities&#xD;
                  are eligible)&#xD;
&#xD;
          -  Mean resting corrected QTc interval using the Fridericia formula (QTcF) &gt; 450&#xD;
             msec/male and &gt; 470 msec/female (as calculated per institutional standards) obtained&#xD;
             from 3 electrocardiograms (ECGs) 2-5 minutes apart at study entry, or congenital long&#xD;
             QT syndrome&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Serious active infection at the time of study entry, or another serious underlying&#xD;
             medical condition that would impair the ability of the patient to receive study&#xD;
             treatment&#xD;
&#xD;
          -  Symptomatic and uncontrolled metastasis in the central nervous system or&#xD;
             leptomeningeal or lymphangitic carcinomatosis&#xD;
&#xD;
          -  Presence of other active invasive cancers that do not harbor CCNE1 amplification&#xD;
&#xD;
          -  Grade 2 or higher peripheral neuropathy&#xD;
&#xD;
          -  Human immunodeficiency virus requiring highly active antiretroviral therapy (HAART)&#xD;
             treatment due to unknown drug-drug interactions or has known active hepatitis B (e.g.,&#xD;
             hepatitis B surface antigen [HBsAg] reactive or C virus [e.g., hepatitis C virus (HCV)&#xD;
             RNA (quantitative) is detected]) infection&#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>Siqing Fu</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Texas MD Anderson Cancer Center LAO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MedStar Georgetown University Hospital</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health Science Center - Gainesville</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky/Markey Cancer Center</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M D Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</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>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <results_first_submitted>July 13, 2023</results_first_submitted>
  <results_first_submitted_qc>August 22, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">September 13, 2023</results_first_posted>
  <last_update_submitted>August 22, 2023</last_update_submitted>
  <last_update_submitted_qc>August 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 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>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adavosertib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 2, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/79/NCT03253679/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Adavosertib)</title>
          <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screen Failure</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Adavosertib)</title>
          <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <population>One participant did not receive any study agent. Thus, 30 patients were considered evaluable</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65" lower_limit="42" upper_limit="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <population>One participant did not receive any study agent. Thus, 30 patients were considered evaluable.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>One participant did not receive any study agent. Thus, 30 patients were considered evaluable</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>ORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.</description>
        <time_frame>Up to 2 years 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Adavosertib)</title>
            <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>ORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.</description>
          <units>percentage</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27" lower_limit="12" upper_limit="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>To Evaluate the Proportion of Patients Alive and Progression Free of Treatment With AZD1775 in Patients With Advanced Refractory Cancers With CCNE1 Amplification.</title>
        <description>Estimated using the Kaplan-Meier Method.</description>
        <time_frame>Up to 2 years 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Adavosertib)</title>
            <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate the Proportion of Patients Alive and Progression Free of Treatment With AZD1775 in Patients With Advanced Refractory Cancers With CCNE1 Amplification.</title>
          <description>Estimated using the Kaplan-Meier Method.</description>
          <units>percentage</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37" lower_limit="20" upper_limit="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>To Evaluate Time Until Death or Disease Progression.</title>
        <description>Estimated using the Kaplan-Meier Method.</description>
        <time_frame>Up to 2 years 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Adavosertib)</title>
            <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>To Evaluate Time Until Death or Disease Progression.</title>
          <description>Estimated using the Kaplan-Meier Method.</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9" lower_limit="4.8" upper_limit="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Responses</title>
        <description>(time to progression on AZD1775/ time to progression on last line of therapy &gt;= 1.3).</description>
        <time_frame>Up to 2 years 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Adavosertib)</title>
            <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Responses</title>
          <description>(time to progression on AZD1775/ time to progression on last line of therapy &gt;= 1.3).</description>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" lower_limit="1.8" upper_limit="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.</title>
        <description>Immunohistochemistry, reverse phase protein arrays, and next generation sequencing for targeted exome panel are used to reveal potential biomarkers predicting major clinical outcomes, and potential mechanisms of acquired resistance by comparing molecular signatures at baseline versus at time of relapse in responders.</description>
        <time_frame>Up to 2 years 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Adavosertib)</title>
            <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.</title>
          <description>Immunohistochemistry, reverse phase protein arrays, and next generation sequencing for targeted exome panel are used to reveal potential biomarkers predicting major clinical outcomes, and potential mechanisms of acquired resistance by comparing molecular signatures at baseline versus at time of relapse in responders.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TP53 gene aberration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AKT2 amplification</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MYC amplification</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CCND2 amplification</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NOTCH1 mutation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 2 years 6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Adavosertib)</title>
          <description>Participants receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE v5</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <description>small bowel obstruction</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Non-hemolytic transfusion reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bladder infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Enterocolitis infections</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diabetic ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboemolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Portal vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE v5</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="28" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALP increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>ALT increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>AST increased</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>WBC decreased</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Siqing Fu</name_or_title>
      <organization>M D Anderson Cancer Center</organization>
      <phone>713-792-4318</phone>
      <email>siqingfu@mdanderson.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03253679
org study id: NCI-2017-01498
secondary id: NCI-2017-01498
secondary id: NCI10136
secondary id: 10136
secondary id: 10136
secondary id: UM1CA186688
nct id: NCT03253679
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well AZD1775 works in treating patients with solid tumors
      with CCNE1 amplification that have spread to other places in the body (advanced) and do not
      respond to treatment (refractory). AZD1775 may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE:

      I. To evaluate the proportion of patients with the objective response rate (ORR) to
      adavosertib (AZD1775) in patients with advanced refractory cancers with CCNE1 amplification.

      SECONDARY OBJECTIVES:

      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment
      with AZD1775 in patients with advanced refractory cancers with CCNE1 amplification.

      II. To evaluate proportion of patients with extended time to progression (time to progression
      on AZD1775/ time to progression on last line of therapy >= 1.3).

      III. To evaluate time until death or disease progression. IV. To identify potential
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and
      imaging-based assessment platforms.

      OUTLINE:

      Patients receive adavosertib orally (PO) once daily (QD) on days 1-5 and 8-12. Cycles repeat
      every 21 days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up for 4 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Up to 2 years 6 months
description: ORR is defined as a complete response or partial response and consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria. The ORR rate will be compared against a null benchmark value of 5%.
measure: To Evaluate the Proportion of Patients Alive and Progression Free of Treatment With AZD1775 in Patients With Advanced Refractory Cancers With CCNE1 Amplification.
time frame: Up to 2 years 6 months
description: Estimated using the Kaplan-Meier Method.
measure: To Evaluate Time Until Death or Disease Progression.
time frame: Up to 2 years 6 months
description: Estimated using the Kaplan-Meier Method.
measure: Duration of Responses
time frame: Up to 2 years 6 months
description: (time to progression on AZD1775/ time to progression on last line of therapy >= 1.3).
measure: Identify Potential Predictive Biomarkers Beyond the Genomic Alteration by Which Treatment is Assigned or Resistance Mechanisms Using Additional Genomic, RNA, Protein and Imaging-based Assessment Platforms.
time frame: Up to 2 years 6 months
description: Immunohistochemistry, reverse phase protein arrays, and next generation sequencing for targeted exome panel are used to reveal potential biomarkers predicting major clinical outcomes, and potential mechanisms of acquired resistance by comparing molecular signatures at baseline versus at time of relapse in responders.
arm group label: Treatment (adavosertib)
arm group type: Experimental
description: Patients receive adavosertib PO QD on days 1-5 and 8-12. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Adavosertib
description: Given PO
arm group label: Treatment (adavosertib)
other name: AZD-1775
other name: AZD1775
other name: MK-1775
other name: MK1775
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Siqing Fu
role: Principal Investigator
affiliation: University of Texas MD Anderson Cancer Center LAO
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country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Adavosertib
provided document: 
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point of contact: 