<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/NCT02196168</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2014-00759</org_study_id>
    <secondary_id>NCI-2014-00759</secondary_id>
    <secondary_id>PHL-088</secondary_id>
    <secondary_id>NCI 9416</secondary_id>
    <secondary_id>PHL-088</secondary_id>
    <secondary_id>9416</secondary_id>
    <secondary_id>N01CM00032</secondary_id>
    <nct_id>NCT02196168</nct_id>
    <nct_alias>NCT01935037</nct_alias>
  </id_info>
  <brief_title>Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer</brief_title>
  <official_title>A Randomized Phase II Trial of Cisplatin With or Without Wee1 Kinase Inhibitor AZD1775 (MK-1775) for First-line Treatment of Recurrent or Metastatic Squamous Cell Cancer of the Head and Neck (RM-SCCHN)</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This randomized phase II trial studies how well cisplatin with or without WEE1 inhibitor&#xD;
      MK-1775 works in treating patients with head and neck cancer that has come back or has spread&#xD;
      to other parts of the body. Drugs used in chemotherapy, such as cisplatin, may prevent tumor&#xD;
      cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the&#xD;
      tumor from growing. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking&#xD;
      some of the enzymes needed for cell growth. It is not yet known whether cisplatin is more&#xD;
      effective with or without WEE1 inhibitor MK-1775 in treating patients with head and neck&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To compare the overall response rate assess the efficacy of MK-1775 (WEE1 inhibitor&#xD;
      MK-1775) in combination with cisplatin to cisplatin alone in patients with recurrent or&#xD;
      metastatic squamous cell carcinoma of the head and neck (SCCHN) as per overall response rate&#xD;
      (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v]1.1).&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Assess secondary measures of efficacy (progression free survival at 6 months and 12&#xD;
      months, overall survival rate at 12 months).&#xD;
&#xD;
      II. Assess measures of efficacy by tumor protein (p)53 status. III. Evaluate safety and&#xD;
      tolerability. IV. Explore predictive and pharmacodynamic biomarkers.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      SAFETY RUN-IN: Patients receive WEE1 inhibitor MK-1775 orally (PO) twice daily (BID) for 5&#xD;
      doses beginning on day 1 and cisplatin intravenously (IV) over 1 hour on day 1. Courses&#xD;
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      Patients are randomized to 1 of 2 treatment arms.&#xD;
&#xD;
      ARM I: Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and&#xD;
      cisplatin IV over 1 hour on day 1.&#xD;
&#xD;
      ARM II: Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over&#xD;
      2 hour on day 1.&#xD;
&#xD;
      In both arms, courses repeat every 21 days in the absence of disease progression or&#xD;
      unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 30 days and then every 3&#xD;
      months for up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Inadequate accrual rate&#xD;
  </why_stopped>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">April 2016</completion_date>
  <primary_completion_date type="Actual">April 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Gr 3, Gr 4 and Gr 5 AEs at least possibly related to study drug</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Pharmacodynamic Biomarkers</measure>
    <time_frame>Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4</time_frame>
    <description>Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of Predictive Biomarkers</measure>
    <time_frame>Up to day 4 of course 1</time_frame>
    <description>Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>12 months</time_frame>
    <description>Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months</time_frame>
    <description>Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (20% increase in the sum of the longest diameter of target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions) or death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months</time_frame>
    <description>Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Recurrent Hypopharyngeal Squamous Cell Carcinoma</condition>
  <condition>Recurrent Laryngeal Squamous Cell Carcinoma</condition>
  <condition>Recurrent Laryngeal Verrucous Carcinoma</condition>
  <condition>Recurrent Lip and Oral Cavity Squamous Cell Carcinoma</condition>
  <condition>Recurrent Metastatic Squamous Cell Carcinoma in the Neck With Occult Primary</condition>
  <condition>Recurrent Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma</condition>
  <condition>Recurrent Oral Cavity Verrucous Carcinoma</condition>
  <condition>Recurrent Oropharyngeal Squamous Cell Carcinoma</condition>
  <condition>Squamous Cell Carcinoma Metastatic in the Neck With Occult Primary</condition>
  <condition>Stage IV Hypopharyngeal Squamous Cell Carcinoma</condition>
  <condition>Stage IVA Laryngeal Squamous Cell Carcinoma</condition>
  <condition>Stage IVA Laryngeal Verrucous Carcinoma</condition>
  <condition>Stage IVA Lip and Oral Cavity Squamous Cell Carcinoma</condition>
  <condition>Stage IVA Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma</condition>
  <condition>Stage IVA Oral Cavity Verrucous Carcinoma</condition>
  <condition>Stage IVA Oropharyngeal Squamous Cell Carcinoma</condition>
  <condition>Stage IVB Laryngeal Squamous Cell Carcinoma</condition>
  <condition>Stage IVB Laryngeal Verrucous Carcinoma</condition>
  <condition>Stage IVB Lip and Oral Cavity Squamous Cell Carcinoma</condition>
  <condition>Stage IVB Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma</condition>
  <condition>Stage IVB Oral Cavity Verrucous Carcinoma</condition>
  <condition>Stage IVB Oropharyngeal Squamous Cell Carcinoma</condition>
  <condition>Stage IVC Laryngeal Squamous Cell Carcinoma</condition>
  <condition>Stage IVC Laryngeal Verrucous Carcinoma</condition>
  <condition>Stage IVC Lip and Oral Cavity Squamous Cell Carcinoma</condition>
  <condition>Stage IVC Nasal Cavity and Paranasal Sinus Squamous Cell Carcinoma</condition>
  <condition>Stage IVC Oral Cavity Verrucous Carcinoma</condition>
  <condition>Stage IVC Oropharyngeal Squamous Cell Carcinoma</condition>
  <condition>Tongue Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm I (WEE1 inhibitor MK-1775, cisplatin)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm II (placebo, cisplatin)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm I (WEE1 inhibitor MK-1775, cisplatin)</arm_group_label>
    <arm_group_label>Arm II (placebo, cisplatin)</arm_group_label>
    <other_name>Abiplatin</other_name>
    <other_name>Blastolem</other_name>
    <other_name>Briplatin</other_name>
    <other_name>CDDP</other_name>
    <other_name>Cis-diammine-dichloroplatinum</other_name>
    <other_name>Cis-diamminedichloridoplatinum</other_name>
    <other_name>Cis-diamminedichloro Platinum (II)</other_name>
    <other_name>Cis-diamminedichloroplatinum</other_name>
    <other_name>Cis-dichloroammine Platinum (II)</other_name>
    <other_name>Cis-platinous Diamine Dichloride</other_name>
    <other_name>Cis-platinum</other_name>
    <other_name>Cis-platinum II</other_name>
    <other_name>Cis-platinum II Diamine Dichloride</other_name>
    <other_name>Cismaplat</other_name>
    <other_name>Cisplatina</other_name>
    <other_name>Cisplatinum</other_name>
    <other_name>Cisplatyl</other_name>
    <other_name>Citoplatino</other_name>
    <other_name>Citosin</other_name>
    <other_name>Cysplatyna</other_name>
    <other_name>DDP</other_name>
    <other_name>Lederplatin</other_name>
    <other_name>Metaplatin</other_name>
    <other_name>Neoplatin</other_name>
    <other_name>Peyrone's Chloride</other_name>
    <other_name>Peyrone's Salt</other_name>
    <other_name>Placis</other_name>
    <other_name>Plastistil</other_name>
    <other_name>Platamine</other_name>
    <other_name>Platiblastin</other_name>
    <other_name>Platiblastin-S</other_name>
    <other_name>Platinex</other_name>
    <other_name>Platinol</other_name>
    <other_name>Platinol- AQ</other_name>
    <other_name>Platinol-AQ</other_name>
    <other_name>Platinol-AQ VHA Plus</other_name>
    <other_name>Platinoxan</other_name>
    <other_name>Platinum</other_name>
    <other_name>Platinum Diamminodichloride</other_name>
    <other_name>Platiran</other_name>
    <other_name>Platistin</other_name>
    <other_name>Platosin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (WEE1 inhibitor MK-1775, cisplatin)</arm_group_label>
    <arm_group_label>Arm II (placebo, cisplatin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Pharmacological Study</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Arm I (WEE1 inhibitor MK-1775, cisplatin)</arm_group_label>
    <arm_group_label>Arm II (placebo, cisplatin)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm II (placebo, cisplatin)</arm_group_label>
    <other_name>placebo therapy</other_name>
    <other_name>PLCB</other_name>
    <other_name>sham therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>WEE1 Inhibitor AZD1775</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm I (WEE1 inhibitor MK-1775, cisplatin)</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 histologically or cytologically confirmed SCCHN that is recurrent&#xD;
             and/or metastatic and not amendable to curative therapy by surgery or radiation; SCCHN&#xD;
             originating from the following sites are eligible: oral cavity, oropharynx, larynx,&#xD;
             hypopharynx and paranasal sinus; for patients with a diagnosis of SCCHN of unknown&#xD;
             origin, their eligibility must be reviewed and approved by the principal investigator&#xD;
&#xD;
          -  No prior systemic chemotherapy or WEE1 kinase inhibitor therapy for metastatic or&#xD;
             recurrent disease will be allowed; patients are permitted to have received prior&#xD;
             systemic chemotherapy as a part of the initial multimodality treatment for locally&#xD;
             advanced disease if this treatment was completed more than 6 months prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Patients must have disease amenable to biopsy and must be medically fit to undergo a&#xD;
             biopsy&#xD;
&#xD;
          -  Patients must have measurable disease, defined as at least one lesion that can be&#xD;
             accurately measured in at least one dimension (longest diameter to be recorded) as &gt;&#xD;
             10 mm with computed tomography (CT) scan; indicator lesions must not have been&#xD;
             previously treated with surgery, radiation therapy or radiofrequency ablation unless&#xD;
             there is documented progression after therapy&#xD;
&#xD;
          -  Patients must have completed any previous surgery or radiotherapy &gt;= 4 weeks prior to&#xD;
             enrollment&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky &gt; 60%)&#xD;
&#xD;
          -  Life expectancy of greater than 12 weeks&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Total bilirubin within normal institutional limits&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 2.5 × institutional upper limit of normal&#xD;
&#xD;
          -  Prothrombin time (PT)/partial thromboplastin time (PTT)/international normalized ratio&#xD;
             (INR) =&lt; 1.5 upper limit of normal (ULN)&#xD;
&#xD;
          -  Creatinine within normal institutional limits OR calculated creatinine clearance &gt;= 60&#xD;
             mL/min/1.73 m^2 for patients with levels above institutional normal using modified&#xD;
             Cockcroft-Gault&#xD;
&#xD;
          -  Cardiac function: 12-lead electrocardiogram (ECG) with normal tracing, or&#xD;
             non-clinically significant changes that do not require medical intervention; corrected&#xD;
             QT (QTc) interval is to be &lt; 470 msec&#xD;
&#xD;
          -  Women of childbearing potential and men must be surgically sterilized, practicing&#xD;
             abstinence, or agree to use 2 birth control methods prior to study entry and for the&#xD;
             duration of study participation including up to 30 days after the last dose of&#xD;
             MK-1775; the 2 methods of birth control can be either 2 barrier methods or a barrier&#xD;
             method plus a hormonal method to prevent pregnancy; the following are considered&#xD;
             adequate barrier methods of contraception: diaphragm or sponge, and condom; other&#xD;
             methods of contraception such as copper intrauterine device or spermicide may be used;&#xD;
             appropriate hormonal contraceptives will include any registered and marketed&#xD;
             contraceptive agent that contains an estrogen and/or a progestational agent (including&#xD;
             oral, subcutaneous, intrauterine, or intramuscular agents); should a woman become&#xD;
             pregnant or suspect she is pregnant while participating in this study, she should&#xD;
             inform her treating physician immediately&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past or current malignancy other than SCCHN, except for:&#xD;
&#xD;
               -  Cervical carcinoma stage 1B or less&#xD;
&#xD;
               -  Non-invasive basal cell and squamous cell skin carcinoma&#xD;
&#xD;
               -  Malignant melanoma with a complete response of a duration of &gt; 10 years&#xD;
&#xD;
               -  Radically treated prostate cancer (prostatectomy or radiotherapy) with normal&#xD;
                  prostate specific antigen (PSA), and not requiring ongoing anti-androgen hormonal&#xD;
                  therapy&#xD;
&#xD;
               -  Other cancer diagnosis with a complete response of duration of &gt; 5 years&#xD;
&#xD;
          -  Patients may not be receiving any other investigational agents&#xD;
&#xD;
          -  Patients with known brain metastases should be excluded from this clinical trial&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to MK-1775 or cisplatin&#xD;
&#xD;
          -  Patients who are unable to take oral medications and/or who have a clinical or&#xD;
             radiological diagnosis of bowel obstruction are ineligible&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to ongoing or active&#xD;
             infection, active peptic ulcer disease, myocardial infarction within 6 months prior to&#xD;
             entry, congestive heart failure, symptomatic congestive heart failure, active&#xD;
             cardiomyopathy, unstable angina pectoris, cardiac arrhythmia, uncontrolled&#xD;
             hypertension or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother is treated with MK-1775&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients are ineligible&#xD;
&#xD;
          -  Patients taking the following prescription or non-prescription drugs or other products&#xD;
             (i.e. grapefruit juice) are ineligible: sensitive cytochrome P450, family 3, subfamily&#xD;
             A, polypeptide 4 (CYP3A4) substrates, CYP3A4 substrates with a narrow therapeutic&#xD;
             index, moderate to potent inhibitors/inducers of CYP3A4; patients would be eligible if&#xD;
             the medications can be discontinued two weeks prior to day 1 of dosing and withheld&#xD;
             throughout the study until 2 weeks after the last dose of study medication&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eric Winquist</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Health Network Princess Margaret Cancer Center P2C</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Juravinski Cancer Centre at Hamilton Health Sciences</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Regional Cancer Program</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Health Network-Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>November 18, 2016</results_first_submitted>
  <results_first_submitted_qc>March 22, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 3, 2017</results_first_posted>
  <last_update_submitted>March 22, 2017</last_update_submitted>
  <last_update_submitted_qc>March 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 3, 2017</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>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Carcinoma, Verrucous</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cisplatin</mesh_term>
    <mesh_term>Adavosertib</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
          <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
        </group>
        <group group_id="P2">
          <title>Arm II (Placebo, Cisplatin)</title>
          <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
          <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
        </group>
        <group group_id="B2">
          <title>Arm II (Placebo, Cisplatin)</title>
          <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="66" lower_limit="56" upper_limit="84"/>
                    <measurement group_id="B3" value="66" lower_limit="56" upper_limit="84"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B3" value="5"/>
                  </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>Canada</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1</title>
        <description>Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1</title>
          <description>Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions</description>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</title>
        <description>Gr 3, Gr 4 and Gr 5 AEs at least possibly related to study drug</description>
        <time_frame>Up to 1 year</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0</title>
          <description>Gr 3, Gr 4 and Gr 5 AEs at least possibly related to study drug</description>
          <units>adverse events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Levels of Pharmacodynamic Biomarkers</title>
        <description>Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.</description>
        <time_frame>Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4</time_frame>
        <population>No data are available as decision was made by PI not to do the analysis due to small number of patients</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Levels of Pharmacodynamic Biomarkers</title>
          <description>Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.</description>
          <population>No data are available as decision was made by PI not to do the analysis due to small number of patients</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Levels of Predictive Biomarkers</title>
        <description>Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.</description>
        <time_frame>Up to day 4 of course 1</time_frame>
        <population>No data are available as decision was made by PI not to do the analysis due to small number of patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Levels of Predictive Biomarkers</title>
          <description>Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.</description>
          <population>No data are available as decision was made by PI not to do the analysis due to small number of patients.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.</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="6"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.21" lower_limit="0.01" upper_limit="0.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival</title>
        <description>Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (20% increase in the sum of the longest diameter of target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions) or death, whichever occurs first.</description>
        <time_frame>Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival</title>
          <description>Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (20% increase in the sum of the longest diameter of target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions) or death, whichever occurs first.</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="6"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.88" lower_limit="0.99" upper_limit="NA">The upper limit for Measure of Dispersion was 'not reached' for this study</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival</title>
        <description>Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.</description>
        <time_frame>Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
            <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
          </group>
          <group group_id="O2">
            <title>Arm II (Placebo, Cisplatin)</title>
            <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival</title>
          <description>Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.</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="6"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.88" lower_limit="0.99" upper_limit="NA">The upper limit for Measure of Dispersion was 'not reached' for this study</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Arm I (WEE1 Inhibitor MK-1775, Cisplatin)</title>
          <description>Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
WEE1 Inhibitor AZD1775: Given PO</description>
        </group>
        <group group_id="E2">
          <title>Arm II (Placebo, Cisplatin)</title>
          <description>Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.&#xD;
Cisplatin: Given IV&#xD;
Laboratory Biomarker Analysis: Correlative studies&#xD;
Pharmacological Study: Correlative studies&#xD;
Placebo: Given PO</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>white blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized Muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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="4" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Febrile Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>white blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>alkalosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized Muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </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.Eric Winquist</name_or_title>
      <organization>London Health Sciences centre</organization>
      <phone>519-685-8500</phone>
      <email>Winquist@lhsc.on.ca</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/NCT02196168
org study id: NCI-2014-00759
secondary id: NCI-2014-00759
secondary id: PHL-088
secondary id: NCI 9416
secondary id: PHL-088
secondary id: 9416
secondary id: N01CM00032
nct id: NCT02196168
nct alias: NCT01935037
lead sponsor: 
has dmc: Yes
This randomized phase II trial studies how well cisplatin with or without WEE1 inhibitor
      MK-1775 works in treating patients with head and neck cancer that has come back or has spread
      to other parts of the body. Drugs used in chemotherapy, such as cisplatin, may prevent tumor
      cells from multiplying by damaging their deoxyribonucleic acid (DNA), which in turn stops the
      tumor from growing. WEE1 inhibitor MK-1775 may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth. It is not yet known whether cisplatin is more
      effective with or without WEE1 inhibitor MK-1775 in treating patients with head and neck
      cancer.
PRIMARY OBJECTIVES:

      I. To compare the overall response rate assess the efficacy of MK-1775 (WEE1 inhibitor
      MK-1775) in combination with cisplatin to cisplatin alone in patients with recurrent or
      metastatic squamous cell carcinoma of the head and neck (SCCHN) as per overall response rate
      (using Response Evaluation Criteria in Solid Tumors [RECIST] criteria version [v]1.1).

      SECONDARY OBJECTIVES:

      I. Assess secondary measures of efficacy (progression free survival at 6 months and 12
      months, overall survival rate at 12 months).

      II. Assess measures of efficacy by tumor protein (p)53 status. III. Evaluate safety and
      tolerability. IV. Explore predictive and pharmacodynamic biomarkers.

      OUTLINE:

      SAFETY RUN-IN: Patients receive WEE1 inhibitor MK-1775 orally (PO) twice daily (BID) for 5
      doses beginning on day 1 and cisplatin intravenously (IV) over 1 hour on day 1. Courses
      repeat every 21 days in the absence of disease progression or unacceptable toxicity.

      Patients are randomized to 1 of 2 treatment arms.

      ARM I: Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and
      cisplatin IV over 1 hour on day 1.

      ARM II: Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over
      2 hour on day 1.

      In both arms, courses repeat every 21 days in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then every 3
      months for up to 1 year.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Overall Response Rate (Complete Plus Partial Response) Using RECIST Criteria v1.1
time frame: Up to 1 year
description: Per Response Evaluation Criteria in solid Tumors (RECIST1.1) Target lesions are assessed as Complete Response(CR), Disappearance of all target lesions; Partial Response (PR),30% decrease in the sum of the diameters of target lesions; Progressive Disease (PD), At least a 20% increase (minimum 5 mm) from smallest sum (nadir); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Nontarget lesions are assessed as Complete Response (CR), Disappearance of all non-target lesions; Non-CR/Non-PD, Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits; Progressive Disease (PD),Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions; Overall Response(OR); PR=CR+non-CR/non-PD,SD=SD+non-PD; PD=PD+presence of any non-target lesions
measure: Incidence of Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
time frame: Up to 1 year
description: Gr 3, Gr 4 and Gr 5 AEs at least possibly related to study drug
measure: Levels of Pharmacodynamic Biomarkers
time frame: Pre-dose, at 4-8 hours on day 3 or 20-24 hours on day 4
description: Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.
measure: Levels of Predictive Biomarkers
time frame: Up to day 4 of course 1
description: Predictors of clinical outcomes will be investigated using logistic regression, Cox proportional hazards regression and/or generalized estimating equations as appropriate. Descriptive statistics and plotting of data will be used to better understand potential relationships.
measure: Overall Survival
time frame: 12 months
description: Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.
measure: Progression Free Survival
time frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 6 months
description: Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression (20% increase in the sum of the longest diameter of target lesions or a measurable increase in a non-target lesion, or the appearance of new lesions) or death, whichever occurs first.
measure: Progression Free Survival
time frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed at 12 months
description: Estimated in each group by the Kaplan Meier method and differences between groups will be calculated by the log rank test. Hazard ratios for each group will be estimated using the Cox Regression model.
arm group label: Arm I (WEE1 inhibitor MK-1775, cisplatin)
arm group type: Experimental
description: Patients receive WEE1 inhibitor MK-1775 PO BID for 5 doses beginning on day 1 and cisplatin IV over 1 hour on day 1.
arm group label: Arm II (placebo, cisplatin)
arm group type: Active Comparator
description: Patients receive placebo PO BID for 5 doses beginning on day 1 and cisplatin IV over 2 hour on day 1.
intervention type: Drug
intervention name: Cisplatin
description: Given IV
arm group label: Arm I (WEE1 inhibitor MK-1775, cisplatin)
arm group label: Arm II (placebo, cisplatin)
other name: Abiplatin
other name: Blastolem
other name: Briplatin
other name: CDDP
other name: Cis-diammine-dichloroplatinum
other name: Cis-diamminedichloridoplatinum
other name: Cis-diamminedichloro Platinum (II)
other name: Cis-diamminedichloroplatinum
other name: Cis-dichloroammine Platinum (II)
other name: Cis-platinous Diamine Dichloride
other name: Cis-platinum
other name: Cis-platinum II
other name: Cis-platinum II Diamine Dichloride
other name: Cismaplat
other name: Cisplatina
other name: Cisplatinum
other name: Cisplatyl
other name: Citoplatino
other name: Citosin
other name: Cysplatyna
other name: DDP
other name: Lederplatin
other name: Metaplatin
other name: Neoplatin
other name: Peyrone's Chloride
other name: Peyrone's Salt
other name: Placis
other name: Plastistil
other name: Platamine
other name: Platiblastin
other name: Platiblastin-S
other name: Platinex
other name: Platinol
other name: Platinol- AQ
other name: Platinol-AQ
other name: Platinol-AQ VHA Plus
other name: Platinoxan
other name: Platinum
other name: Platinum Diamminodichloride
other name: Platiran
other name: Platistin
other name: Platosin
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Arm I (WEE1 inhibitor MK-1775, cisplatin)
arm group label: Arm II (placebo, cisplatin)
intervention type: Other
intervention name: Pharmacological Study
description: Correlative studies
arm group label: Arm I (WEE1 inhibitor MK-1775, cisplatin)
arm group label: Arm II (placebo, cisplatin)
intervention type: Other
intervention name: Placebo
description: Given PO
arm group label: Arm II (placebo, cisplatin)
other name: placebo therapy
other name: PLCB
other name: sham therapy
intervention type: Drug
intervention name: WEE1 Inhibitor AZD1775
description: Given PO
arm group label: Arm I (WEE1 inhibitor MK-1775, cisplatin)
other name: AZD-1775
other name: AZD1775
other name: MK-1775
other name: MK1775
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Eric Winquist
role: Principal Investigator
affiliation: University Health Network Princess Margaret Cancer Center P2C
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Carcinoma, Verrucous
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Recurrence
mesh term: Cisplatin
mesh term: Adavosertib
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 