<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/NCT04460937</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-04698</org_study_id>
    <secondary_id>NCI-2020-04698</secondary_id>
    <secondary_id>10389</secondary_id>
    <secondary_id>10389</secondary_id>
    <secondary_id>UM1CA186712</secondary_id>
    <nct_id>NCT04460937</nct_id>
  </id_info>
  <brief_title>Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers</brief_title>
  <official_title>A Phase 1 Trial Combining WEE1 Inhibitor Adavosertib (AZD1775) With Radiation Therapy for Metastatic or Inoperable and Ineligible for Definitive Chemoradiation Esophageal and Gastroesophageal Junction Cancer</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>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial investigates the side effects and best dose of adavosertib and how well it&#xD;
      works when given in combination with radiation therapy in treating patients with esophageal&#xD;
      or gastroesophageal junction cancer for which no treatment is currently available&#xD;
      (incurable). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes&#xD;
      needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and&#xD;
      shrink tumors. Giving adavosertib together with radiation therapy kill more tumor cells than&#xD;
      radiation therapy alone in treating patients with esophageal and gastroesophageal junction&#xD;
      cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To identify the maximally tolerated dose of adavosertib (AZD1775) to be used in&#xD;
      combination with radiation therapy for patients with esophageal/gastroesophageal junction&#xD;
      (GEJ) cancer that is metastatic or inoperable and not eligible for definitive chemoradiation.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To observe and record anti-tumor activity. II. To evaluate the efficacy of AZD1775 when&#xD;
      administered in combination with radiation therapy by assessing changes in Ogilvie dysphagia&#xD;
      score following treatment, time to second intervention for dysphagia, and overall survival.&#xD;
&#xD;
      III. To identify biomarkers that are predictive for response to experimental therapy.&#xD;
&#xD;
      OUTLINE: This is a dose escalation study of adavosertib.&#xD;
&#xD;
      Patients undergo radiation therapy once daily (QD) 5 days per week for 3 weeks in the absence&#xD;
      of disease progression or unacceptable toxicity. Patients also receive adavosertib orally&#xD;
      (PO) QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in&#xD;
      the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up at 3 weeks, every 3 months for&#xD;
      2 years, then every 6 months for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 7, 2020</start_date>
  <completion_date type="Anticipated">October 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD)</measure>
    <time_frame>After completion of treatment</time_frame>
    <description>Will employ a BOIN design where the target toxicity rate for the MTD is 25% with 75% dose-elimination cut-off.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized with descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Symptom relief rate</measure>
    <time_frame>After completion of treatment</time_frame>
    <description>Will be calculated with 95% binomial confidence intervals.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to second intervention for dysphagia</measure>
    <time_frame>The time from initiation of therapy to the time of second intervention for dysphagia, assessed up to 5 years</time_frame>
    <description>Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>From date of patient enrollment to death due to any cause, assessed up to 5 years after completion of treatment</time_frame>
    <description>Survival will initially be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% confidence interval (CI).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ogilvie dysphagia scores</measure>
    <time_frame>At baseline and after completion of treatment</time_frame>
    <description>The scores will be summarized and compared using paired t-test or Wilcoxon signed-rank test. Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>Will be described graphically or summary measures (e.g. mean and standard errors, or median and range) and compared between responders and non-responders using a two sample t-test or Wilcoxon test if the data is not normally distributed.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">33</enrollment>
  <condition>Clinical Stage III Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage III Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage IV Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage IV Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage IVA Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Clinical Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage IVB Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Clinical Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Clinical Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Distal Esophagus Adenocarcinoma</condition>
  <condition>Gastric Cardia Adenocarcinoma</condition>
  <condition>Metastatic Esophageal Adenocarcinoma</condition>
  <condition>Metastatic Esophageal Squamous Cell Carcinoma</condition>
  <condition>Metastatic Gastroesophageal Junction Adenocarcinoma</condition>
  <condition>Metastatic Malignant Neoplasm in the Brain</condition>
  <condition>Metastatic Malignant Neoplasm in the Leptomeninges</condition>
  <condition>Pathologic Stage III Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage III Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Pathologic Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IIIA Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Pathologic Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IIIB Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Pathologic Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IV Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IV Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Pathologic Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IVA Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Pathologic Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IVB Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Pathologic Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Pathologic Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage III Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage III Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IIIA Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IIIA Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IIIA Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IIIB Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IIIB Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IIIB Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IV Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IV Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IVA Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IVA Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IVA Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IVB Esophageal Adenocarcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IVB Esophageal Squamous Cell Carcinoma AJCC v8</condition>
  <condition>Postneoadjuvant Therapy Stage IVB Gastroesophageal Junction Adenocarcinoma AJCC v8</condition>
  <condition>Unresectable Esophageal Adenocarcinoma</condition>
  <condition>Unresectable Esophageal Carcinoma</condition>
  <condition>Unresectable Esophageal Squamous Cell Carcinoma</condition>
  <condition>Unresectable Gastroesophageal Junction Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (radiation therapy, adavosertib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients undergo radiation therapy QD 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib PO QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy 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 (radiation therapy, 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>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Radiation Therapy</intervention_name>
    <description>Undergo radiation therapy</description>
    <arm_group_label>Treatment (radiation therapy, adavosertib)</arm_group_label>
    <other_name>Cancer Radiotherapy</other_name>
    <other_name>Energy Type</other_name>
    <other_name>ENERGY_TYPE</other_name>
    <other_name>Irradiate</other_name>
    <other_name>Irradiated</other_name>
    <other_name>Irradiation</other_name>
    <other_name>Radiation</other_name>
    <other_name>Radiation Therapy, NOS</other_name>
    <other_name>Radiotherapeutics</other_name>
    <other_name>Radiotherapy</other_name>
    <other_name>RT</other_name>
    <other_name>Therapy, Radiation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically confirmed esophageal cancer (either squamous cell or&#xD;
             adenocarcinoma), including Siewert gastroesophageal junction adenocarcinomas types 1&#xD;
             and 2, that is inoperable and not eligible for definitive chemoradiation after&#xD;
             multidisciplinary review or have pathologically confirmed or imaging consistent with&#xD;
             metastatic disease&#xD;
&#xD;
          -  Age &gt;= 18 years. Because no dosing or adverse event data are currently available on&#xD;
             the use of AZD1775 in combination with radiation therapy in patients &lt; 18 years of&#xD;
             age, children are excluded from this study&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky &gt;= 70%)&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Platelets &gt;= 100,000/mcL&#xD;
&#xD;
          -  Total bilirubin =&lt; 1.5 x institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase&#xD;
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])&#xD;
             =&lt; 3 x institutional ULN&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 x institutional ULN OR&#xD;
&#xD;
          -  Glomerular filtration rate (GFR) &gt;= 60 mL /min/1.73 m^2 unless data exists supporting&#xD;
             safe use at lower kidney function values, no lower than 30 mL/min/1.73 m^2&#xD;
&#xD;
          -  For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral&#xD;
             load must be undetectable on suppressive therapy, if indicated&#xD;
&#xD;
          -  Patients with a history of hepatitis C virus (HCV) infection must have been treated&#xD;
             and cured. For patients with HCV infection who are currently on treatment, they are&#xD;
             eligible if they have an undetectable HCV viral load&#xD;
&#xD;
          -  Patients with treated brain metastases are eligible if follow-up brain imaging after&#xD;
             central nervous system (CNS)-directed therapy shows no evidence of progression&#xD;
&#xD;
          -  Patients with new or progressive brain metastases (active brain metastases) or&#xD;
             leptomeningeal disease are eligible if the treating physician determines that&#xD;
             immediate CNS specific treatment is not required and is unlikely to be required during&#xD;
             the first cycle of therapy&#xD;
&#xD;
          -  Patients with a prior or concurrent malignancy whose natural history or treatment does&#xD;
             not have the potential to interfere with the safety or efficacy assessment of the&#xD;
             investigational regimen are eligible for this trial&#xD;
&#xD;
          -  Patients with known history or current symptoms of cardiac disease, or history of&#xD;
             treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac&#xD;
             function using the New York Heart Association Functional Classification. To be&#xD;
             eligible for this trial, patients should be class 2B or better&#xD;
&#xD;
          -  Patients able to swallow whole capsules. Patients with esophageal stents and/or&#xD;
             feeding tubes are eligible but must be able to swallow whole capsules. Capsules may&#xD;
             not be opened or put down a feeding tube&#xD;
&#xD;
          -  Patients with a life expectancy &gt; 3 months&#xD;
&#xD;
          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment&#xD;
             assignment and must have no clinically important abnormalities in rhythm, conduction&#xD;
             or morphology of resting ECG&#xD;
&#xD;
               -  Resting corrected QTc interval using the Fridericia formula (QTcF) &gt; 480 msec (as&#xD;
                  calculated per institutional standards) obtained from an ECG (Note: if one ECG&#xD;
                  demonstrates a QTcF &gt; 480 msec, then a mean QTcF of =&lt; 480 msec obtained from 3&#xD;
                  ECGs 2-5 minutes apart, is required at study entry)&#xD;
&#xD;
               -  Patients with congenital long QT syndrome are excluded&#xD;
&#xD;
          -  The effects of AZD1775 on the developing human fetus are unknown. For this reason and&#xD;
             because other therapeutic agents used in this trial are known to be teratogenic, women&#xD;
             of child-bearing potential must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) for 2 weeks prior to study drug exposure,&#xD;
             the duration of study participation, and for 1 month after completing treatment. Women&#xD;
             of child-bearing potential must have a negative serum or urine pregnancy test (minimum&#xD;
             sensitivity 25 IU/L or equivalent units of HCG) within 1 week of registration. Should&#xD;
             a woman become pregnant or suspect she is pregnant while she or her partner is&#xD;
             participating in this study, she should inform her treating physician immediately. Men&#xD;
             treated or enrolled on this protocol must also agree to use adequate contraception for&#xD;
             the duration of study participation and for 3 months after completion of treatment.&#xD;
             Male patients should not donate sperm during exposure to study drug and for 3 months&#xD;
             after study drug discontinuation&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
             Participants with impaired decision-making capacity (IDMC) will also be eligible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have had chemotherapy or radiotherapy within 3 weeks (6 weeks for&#xD;
             nitrosoureas or mitomycin C) prior to starting study therapy&#xD;
&#xD;
          -  Patients who have not recovered from adverse events due to prior anti-cancer therapy&#xD;
             (i.e., have residual toxicities &gt; grade 1) with the exception of alopecia&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to AZD1775&#xD;
&#xD;
          -  Patients receiving any medications or substances that are strong inhibitors or&#xD;
             inducers of CYP3A4 are ineligible. Because the lists of these agents are constantly&#xD;
             changing, it is important to regularly consult a frequently-updated medical reference.&#xD;
             As part of the enrollment/informed consent procedures, the patient will be counseled&#xD;
             on the risk of interactions with other agents, and what to do if new medications need&#xD;
             to be prescribed or if the patient is considering a new over-the-counter medicine or&#xD;
             herbal product&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness&#xD;
&#xD;
          -  Patients with psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements&#xD;
&#xD;
          -  Pregnant women are excluded from this study because AZD1775 is a WEE1 inhibiting agent&#xD;
             with the potential for teratogenic or abortifacient effects. Because there is an&#xD;
             unknown but potential risk for adverse events in nursing infants secondary to&#xD;
             treatment of the mother with AZD1775, breastfeeding should be discontinued if the&#xD;
             mother is treated with AZD1775. These potential risks may also apply to other agents&#xD;
             used in this study&#xD;
&#xD;
          -  Prior thoracic or abdominal radiation therapy for cancer that would result in&#xD;
             significant overlap of radiation therapy fields at the discretion of the investigator&#xD;
&#xD;
          -  Patients with congenital long QT syndrome or with a history of Torsades de pointes&#xD;
             unless all risk factors contributed to Torsades have been corrected. AZD1775 has not&#xD;
             been studied in patients with ventricular arrhythmias or recent myocardial infarction&#xD;
&#xD;
          -  Eligibility of subjects receiving any medications or substances with the potential to&#xD;
             affect the activity or pharmacokinetics of AZD1775 will be determined following review&#xD;
             by the principal investigator&#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>Eric D Miller</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ohio State University Comprehensive 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>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</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>Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</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>University of Utah Sugarhouse Health Center</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 8, 2020</study_first_posted>
  <last_update_submitted>August 8, 2023</last_update_submitted>
  <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Esophageal Squamous Cell Carcinoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Second Primary</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adavosertib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.</ipd_description>
    <ipd_url>https://grants.nih.gov/policy/sharing.htm</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04460937
org study id: NCI-2020-04698
secondary id: NCI-2020-04698
secondary id: 10389
secondary id: 10389
secondary id: UM1CA186712
nct id: NCT04460937
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial investigates the side effects and best dose of adavosertib and how well it
      works when given in combination with radiation therapy in treating patients with esophageal
      or gastroesophageal junction cancer for which no treatment is currently available
      (incurable). Adavosertib may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and
      shrink tumors. Giving adavosertib together with radiation therapy kill more tumor cells than
      radiation therapy alone in treating patients with esophageal and gastroesophageal junction
      cancer.
PRIMARY OBJECTIVE:

      I. To identify the maximally tolerated dose of adavosertib (AZD1775) to be used in
      combination with radiation therapy for patients with esophageal/gastroesophageal junction
      (GEJ) cancer that is metastatic or inoperable and not eligible for definitive chemoradiation.

      SECONDARY OBJECTIVES:

      I. To observe and record anti-tumor activity. II. To evaluate the efficacy of AZD1775 when
      administered in combination with radiation therapy by assessing changes in Ogilvie dysphagia
      score following treatment, time to second intervention for dysphagia, and overall survival.

      III. To identify biomarkers that are predictive for response to experimental therapy.

      OUTLINE: This is a dose escalation study of adavosertib.

      Patients undergo radiation therapy once daily (QD) 5 days per week for 3 weeks in the absence
      of disease progression or unacceptable toxicity. Patients also receive adavosertib orally
      (PO) QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in
      the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 3 weeks, every 3 months for
      2 years, then every 6 months for 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: After completion of treatment
description: Will employ a BOIN design where the target toxicity rate for the MTD is 25% with 75% dose-elimination cut-off.
measure: Incidence of adverse events
time frame: Up to 5 years
description: Frequency and severity of adverse events and tolerability of the regimen will be collected and summarized with descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
measure: Symptom relief rate
time frame: After completion of treatment
description: Will be calculated with 95% binomial confidence intervals.
measure: Time to second intervention for dysphagia
time frame: The time from initiation of therapy to the time of second intervention for dysphagia, assessed up to 5 years
description: Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores
measure: Overall survival
time frame: From date of patient enrollment to death due to any cause, assessed up to 5 years after completion of treatment
description: Survival will initially be analyzed using Kaplan-Meier methods, resulting in median survival times with 95% confidence interval (CI).
measure: Ogilvie dysphagia scores
time frame: At baseline and after completion of treatment
description: The scores will be summarized and compared using paired t-test or Wilcoxon signed-rank test. Patient dysphagia will be evaluated using the Ogilvie dysphagia score, comparing pre-treatment to post-treatment scores.
measure: Biomarkers
time frame: Up to 5 years
description: Will be described graphically or summary measures (e.g. mean and standard errors, or median and range) and compared between responders and non-responders using a two sample t-test or Wilcoxon test if the data is not normally distributed.
arm group label: Treatment (radiation therapy, adavosertib)
arm group type: Experimental
description: Patients undergo radiation therapy QD 5 days per week for 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also receive adavosertib PO QD for 2-5 days (depending on dose level) during weeks 1 and 3 of radiation therapy in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Adavosertib
description: Given PO
arm group label: Treatment (radiation therapy, adavosertib)
other name: AZD-1775
other name: AZD1775
other name: MK-1775
other name: MK1775
intervention type: Radiation
intervention name: Radiation Therapy
description: Undergo radiation therapy
arm group label: Treatment (radiation therapy, adavosertib)
other name: Cancer Radiotherapy
other name: Energy Type
other name: ENERGY_TYPE
other name: Irradiate
other name: Irradiated
other name: Irradiation
other name: Radiation
other name: Radiation Therapy, NOS
other name: Radiotherapeutics
other name: Radiotherapy
other name: RT
other name: Therapy, Radiation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Eric D Miller
role: Principal Investigator
affiliation: Ohio State University Comprehensive Cancer Center LAO
facility: 
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Carcinoma, Squamous Cell
mesh term: Adenocarcinoma
mesh term: Esophageal Squamous Cell Carcinoma
mesh term: Esophageal Neoplasms
mesh term: Neoplasms, Second Primary
mesh term: Adavosertib
sharing ipd: Yes
ipd description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
ipd url: https://grants.nih.gov/policy/sharing.htm