<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/NCT03040986</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2017-00118</org_study_id>
    <secondary_id>NCI-2017-00118</secondary_id>
    <secondary_id>17C0144</secondary_id>
    <secondary_id>10050</secondary_id>
    <secondary_id>10050</secondary_id>
    <secondary_id>ZIABC011078</secondary_id>
    <nct_id>NCT03040986</nct_id>
  </id_info>
  <brief_title>Selumetinib Sulfate in Treating Patients With Locally Advanced or Metastatic Pancreatic Cancer With KRAS G12R Mutations</brief_title>
  <official_title>A Phase II Study of Selumetinib (AZD6244) for the Treatment of Advanced Pancreas Cancer Harboring KRAS G12R Mutations</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 II trial studies how well selumetinib sulfate works in treating patients with&#xD;
      pancreatic cancer with Kirsten rat sarcoma (KRAS) G12R mutations that has spread from where&#xD;
      it started to nearby tissue or lymph nodes or other places in the body. Selumetinib sulfate&#xD;
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Determine the objective response rate to selumetinib sulfate (selumetinib) administered as&#xD;
      75 mg orally twice daily on a continuous schedule in patients with advanced pancreas cancer&#xD;
      harboring Kirsten rat sarcoma (KRAS) G12R mutations.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the progression free survival of patients with locally advanced, unresectable&#xD;
      and stage IV pancreas cancer treated with selumetinib monotherapy.&#xD;
&#xD;
      II. To evaluate the safety of selumetinib in patients with advanced pancreas cancer.&#xD;
&#xD;
      III. To determine the impact of additional genetic alterations on the response to selumetinib&#xD;
      in pancreas cancer harboring KRAS G12R mutations.&#xD;
&#xD;
      IV. To develop a clinically applicable biomarker predicting response to selumetinib in&#xD;
      pancreas cancer harboring KRAS G12R mutations.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive selumetinib sulfate orally (PO) twice daily (BID). Treatment repeats every&#xD;
      28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 2 months for 52 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 21, 2017</start_date>
  <completion_date type="Actual">October 15, 2020</completion_date>
  <primary_completion_date type="Actual">August 10, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of Participants With an Objective Response (Partial Response + Complete Response)</measure>
    <time_frame>Approximately 1-8.2 months</time_frame>
    <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10mm (&lt;1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Progression-free Survival (PFS)</measure>
    <time_frame>From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks</time_frame>
    <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first and was calculated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 25 months and 6 days.</time_frame>
    <description>Here are the grade 3 or greater adverse events assessed by the CTCAEv5.0 probably or definitely attributable to the agent Selumetinib. Grade 3 is defined as severe or medically significant, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. Probably is defined as likely related to the agent, and Definitely is defined as clearly related to the agent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</measure>
    <time_frame>Date treatment consent signed to date off study, approximately 25 months and 6 days.</time_frame>
    <description>Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Semi-quantitative Measurements of Connector Enhancer of the Kinase Suppressor of Ras-1 (CNKSR1)</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Comparisons will be done to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predictive Biomarkers for Response to Selumetinib</measure>
    <time_frame>Up to 52 weeks</time_frame>
    <description>Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be &gt; and &lt; 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in participants with cell free deoxyribonucleic acid (cfDNA) transcripts levels &gt; 2 standard deviation (SD) above the mean, participants with cfDNA transcripts levels &lt; 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Longitudinal Biomarker Measuring Response to Treatment</measure>
    <time_frame>start of treatment every (q)2 weeks, up to 52 weeks</time_frame>
    <description>Circulating free deoxyribonucleic acid (cfDNA) transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Somatic Circulating Tumor Deoxyribonucleic Acid (ctDNA) Mutation Profile and Its Correlation With Clinical Outcome</measure>
    <time_frame>Baseline up to 52 weeks</time_frame>
    <description>The presence of mutant DNA copies and the fractional abundance of the mutant KRAS allele on circulating tumor DNA (ctDNA) in cell-free (cf) DNA isolated from plasma samples were to be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA)</measure>
    <time_frame>Baseline and the last KRAS value before the participant came off treatment, approximately 1- 8.2 months.</time_frame>
    <description>ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined from baseline and the last KRAS value (as a single value) before the participant came off treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Percentage Change (%) of Copies KRAS Wild Type Allele</measure>
    <time_frame>Approximately 1- 8.2 months.</time_frame>
    <description>Overall ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA)</measure>
    <time_frame>Baseline and last recorded value while on treatment, approximately 1- 8.2 months.</time_frame>
    <description>Mean ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined at baseline and the last recorded value while on treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Percentage Change of Copies KRAS Mutant Type Allele</measure>
    <time_frame>Approximately 1- 8.2 months.</time_frame>
    <description>Overall ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA</measure>
    <time_frame>Between baseline and last recorded value while on-treatment, approximately 1- 8.2 months.</time_frame>
    <description>This outcome measure is reporting the overall percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples between baseline and on-treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Any Percent Change in (VAF, %), of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA)</measure>
    <time_frame>Approximately 1- 8.2 months.</time_frame>
    <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value while on-treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline</measure>
    <time_frame>Baseline and last recorded value while on-treatment, approximately 1- 8.2 months.</time_frame>
    <description>Any change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline</measure>
    <time_frame>Approximately 1- 8.2 months.</time_frame>
    <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment</measure>
    <time_frame>Baseline and last recorded value after treatment, approximately 1- 8.2 months.</time_frame>
    <description>This outcome measure is reporting the percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value after treatment in patients with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) (Mutant Fractional KRAS Abundency at baseline and after treatment (VAF %), KRAS allele at baseline &gt; 0%).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants With Detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment</measure>
    <time_frame>Approximately 1- 8.2 months.</time_frame>
    <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) between baseline and last recorded value after treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>KRAS NP_004976.2:p.G12R</condition>
  <condition>Stage III Pancreatic Cancer AJCC v6 and v7</condition>
  <condition>Stage IV Pancreatic Cancer AJCC v6 and v7</condition>
  <arm_group>
    <arm_group_label>Treatment (selumetinib sulfate)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (selumetinib sulfate)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Selumetinib Sulfate</intervention_name>
    <description>Given by mouth (PO)</description>
    <arm_group_label>Treatment (selumetinib sulfate)</arm_group_label>
    <other_name>AZD-6244 Hydrogen Sulfate</other_name>
    <other_name>AZD6244 Hydrogen Sulfate</other_name>
    <other_name>AZD6244 Hydrogen Sulphate</other_name>
    <other_name>Selumetinib Sulphate</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologically confirmed locally advanced or metastatic pancreas&#xD;
             cancer&#xD;
&#xD;
          -  Patients must have received at least 6 months fluorouracil (5-FU)- or&#xD;
             gemcitabine-based treatments for pancreas cancer (fluorouracil, irinotecan&#xD;
             hydrochloride, leucovorin calcium and oxaliplatin [FOLFIRINOX], fluorouracil,&#xD;
             leucovorin calcium and oxaliplatin [FOLFOX], 5-FU+ nal-IRI [MM-398; nanoliposomal&#xD;
             irinotecan], or 5-FU [including capecitabine], gemcitabine-based gemcitabine plus&#xD;
             abraxane, gemcitabine monotherapy among others)&#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 for&#xD;
             non-nodal lesions and short axis for nodal lesions) as &gt;= 20 mm (&gt;= 2 cm) with&#xD;
             conventional techniques or as &gt;= 10 mm (&gt;= 1 cm) with spiral computed tomography (CT)&#xD;
             scan, magnetic resonance imaging (MRI), or calipers by clinical exam&#xD;
&#xD;
          -  Patients must have Clinical Laboratory Improvement Act (CLIA) confirmed somatic&#xD;
             Kirsten rat sarcoma (KRAS) G12R mutation as determined by sequence analysis of matched&#xD;
             normal deoxyribonucleic acid (DNA) from any specimen obtained from the individual;&#xD;
             patients must provide tumor sample for KRAS analysis or be willing to undergo&#xD;
             mandatory screening biopsy&#xD;
&#xD;
          -  Patients must not have had chemotherapy, molecular therapy with erlotinib, radiation&#xD;
             therapy, or experimental biological or molecular therapy for at least 4 weeks prior to&#xD;
             starting study medication; patients who received FOLFIRINOX must be 6 weeks from the&#xD;
             last administration of therapy; patients must have recovered from any acute toxicity&#xD;
             related to prior therapy or surgery, to a grade 1 or less unless specified&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 1 or Karnofsky &gt;= 70%&#xD;
&#xD;
          -  Leukocytes &gt;= 3,000/mcL&#xD;
&#xD;
          -  Absolute neutrophil count &gt;= 1,500/mcL&#xD;
&#xD;
          -  Platelets &gt;= 75,000/mcL&#xD;
&#xD;
          -  Hemoglobin (Hgb) &gt;= 9.0 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 glutamic pyruvic transaminase [SGPT]) &lt;&#xD;
             3 x institutional upper limit of normal&#xD;
&#xD;
          -  Creatinine =&lt; institutional upper limit of normal OR&#xD;
&#xD;
          -  Creatinine clearance &gt; 60 mL/min/1.73 m^2 by either Cockcroft-Gault formula or 24-hour&#xD;
             urine collection analysis&#xD;
&#xD;
          -  Patients must be willing to return to the clinic for follow-up visits&#xD;
&#xD;
          -  Women of child-bearing potential must agree to use adequate contraception (hormonal or&#xD;
             barrier method of birth control; abstinence) prior to study entry, for the duration of&#xD;
             study participation, and for 4 weeks after dosing with selumetinib sulfate (AZD6244)&#xD;
             ceases; women of child-bearing potential must have a negative pregnancy test within 14&#xD;
             days prior to study treatment; should a woman become pregnant or suspect she is&#xD;
             pregnant while she or her partner is participating in this study, the patient should&#xD;
             inform her treating physician immediately; please note that the AZD6244 manufacturer&#xD;
             recommends that adequate contraception for male patients should be used for 12 weeks&#xD;
             post-last dose due to sperm life cycle; NOTE: breastfeeding should be discontinued if&#xD;
             the mother is treated with selumetinib&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document&#xD;
             or patients with Impaired Decision Making Capacity (IDMC) if they are represented by a&#xD;
             Legally Authorized Representative (LAR)&#xD;
&#xD;
          -  Patient must be able to reliably swallow oral medications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have received prior treatment with tyrosine kinase inhibitors (e.g.&#xD;
             erlotinib), or anti-Epidermal growth factor receptor (EGFR) agents (e.g. cetuximab,&#xD;
             panitumumab)&#xD;
&#xD;
          -  Patients currently receiving any medication known to induce central serous&#xD;
             chorioretinopathy which in the opinion of the principal investigator, would make the&#xD;
             administration of study drug hazardous&#xD;
&#xD;
          -  Patients with active hepatic or biliary disease (with exception of patients with&#xD;
             Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver&#xD;
             disease per investigator assessment)&#xD;
&#xD;
          -  Patients with uncontrolled intercurrent illness including, but not limited to, ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, or psychiatric illness/social situations that would limit&#xD;
             compliance with study requirements&#xD;
&#xD;
          -  Any underlying medical condition which, in the opinion of the principal investigator,&#xD;
             will make the administration of study drug hazardous or obscure the interpretation of&#xD;
             adverse events&#xD;
&#xD;
          -  Patients who are receiving any other investigational agents&#xD;
&#xD;
          -  Patients with known brain metastases should be excluded from this clinical trial; no&#xD;
             additional workup is needed to exclude brain metastases if the patient is asymptomatic&#xD;
             or has no history of brain metastases&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to Selumetinib (AZD6244) or other agents used in study&#xD;
&#xD;
          -  Previous Mitogen-activated protein kinase kinase (MEK), RAS, or Rapidly Accelerated&#xD;
             Fibrosarcoma (RAF) inhibitor use&#xD;
&#xD;
          -  Patients with the following cardiac conditions are excluded:&#xD;
&#xD;
               -  Uncontrolled hypertension (blood pressure [BP] of &gt;= 150/95 despite medical&#xD;
                  support/management)&#xD;
&#xD;
               -  Acute coronary syndrome within 6 months prior to starting treatment&#xD;
&#xD;
               -  Uncontrolled angina - Canadian Cardiovascular Society grade II-IV despite medical&#xD;
                  support/management&#xD;
&#xD;
               -  Heart failure New York Heart Association (NYHA) class II or above&#xD;
&#xD;
               -  Prior or current cardiomyopathy (within 6 months) including but not limited to&#xD;
                  the following:&#xD;
&#xD;
                    -  Known hypertrophic cardiomyopathy&#xD;
&#xD;
                    -  Known arrhythmogenic right ventricular cardiomyopathy&#xD;
&#xD;
                    -  Abnormal ejection fraction (echocardiogram [ECHO]) =&lt; 53% (if a range is&#xD;
                       given then the upper value of the range will be used) or cardiac magnetic&#xD;
                       resonance imaging (MRI)&#xD;
&#xD;
                    -  Previous moderate or severe impairment of left ventricular systolic function&#xD;
                       (left ventricular ejection fraction [LVEF] &lt; 45% on echocardiography or&#xD;
                       equivalent on multi-gated acquisition scan [MUGA]) even if full recovery has&#xD;
                       occurred; echocardiogram (Echo) and additional cardiac studies not indicated&#xD;
                       unless clinically symptomatic or patient has significant cardiac history&#xD;
&#xD;
                    -  Severe valvular heart disease&#xD;
&#xD;
                    -  Atrial fibrillation with a ventricular rate &gt; 100 beats per minute (bpm) on&#xD;
                       electrocardiogram (ECG) at rest&#xD;
&#xD;
                    -  Fridericia's corrected QT interval (QTcF) &gt;= 450 msec or other factors that&#xD;
                       increase the risk of QT prolongation or arrhythmic events (e.g., heart&#xD;
                       failure, hypokalemia, family history of long QT interval syndrome) are&#xD;
                       excluded; the use of medication(s) that can prolong QTc interval is&#xD;
                       prohibited while treated on this study&#xD;
&#xD;
          -  Patients with known ophthalmologic conditions, such as:&#xD;
&#xD;
               -  Current or past history of central serous retinopathy&#xD;
&#xD;
               -  Current or past history of retinal vein occlusion&#xD;
&#xD;
               -  Known intraocular pressure (IOP) &gt; 21 mmHg (or upper limit of normal [ULN]&#xD;
                  adjusted by age) or uncontrolled glaucoma (irrespective of IOP); patients with&#xD;
                  controlled glaucoma and increased IOP who do not have meaningful vision (light&#xD;
                  perception only or no light perception) may be eligible after discussion with the&#xD;
                  study chair&#xD;
&#xD;
               -  Subjects with any other significant abnormality on ophthalmic examination&#xD;
                  (performed by an ophthalmologist) should be discussed with the study chair for&#xD;
                  potential eligibility&#xD;
&#xD;
               -  Ophthalmological findings secondary to long-standing optic pathway glioma (such&#xD;
                  as visual loss, optic nerve pallor or strabismus) or long-standing&#xD;
                  orbito-temporal plexiform neurofibroma (PN) (such as visual loss, strabismus)&#xD;
                  will NOT be considered a significant abnormality for the purposes of the study&#xD;
&#xD;
          -  Patients with refractory nausea and vomiting, chronic gastrointestinal (GI) diseases&#xD;
             (e.g., inflammatory bowel disease) or significant bowel resection&#xD;
&#xD;
          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral&#xD;
             therapy are ineligible; HIV-positive patients not on antiviral therapy with&#xD;
             undetectable viral loads and cluster of differentiation 4 (CD4) counts &gt; 300, and&#xD;
             after confirmation of eligibility after discussing with the study chair are eligible&#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>Udo Rudloff</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Cancer Institute LAO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Los Angeles County-USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</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>NCI - Center for Cancer Research</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wayne State University/Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>February 1, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 2, 2017</study_first_posted>
  <results_first_submitted>October 18, 2020</results_first_submitted>
  <results_first_submitted_qc>December 16, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 11, 2021</results_first_posted>
  <last_update_submitted>January 20, 2021</last_update_submitted>
  <last_update_submitted_qc>January 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2021</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>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03040986/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 19, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03040986/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>180 pts were not enrolled to the study. All pts who made contact to participate in the study all had KRAS G12R mutation testing thus pre-screening was not necessary. The 1st 8 pts who made contact with the study and were eligible were consented, enrolled and treated. No other pts were enrolled in the study per the statistical design in the protocol. As pre-specified, the study did not move into the second phase due to lack of efficacy.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
          <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="P2">
          <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
          <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Hospice</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression on study</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
          <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="B2">
          <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
          <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</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="2"/>
            <count group_id="B3" value="8"/>
          </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="B2" 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="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" spread="8.99"/>
                    <measurement group_id="B2" value="59" spread="7.07"/>
                    <measurement group_id="B3" value="60.5" spread="8.03"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Location of Primary Tumor</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Head/Body</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tail</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Previous Treatments</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Radiation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Surgery</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Multiple agents systemic chemotherapy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Previous Lines of Systemic Chemotherapy</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Metastatic Sites (involved organs)</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>≥3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants With an Objective Response (Partial Response + Complete Response)</title>
        <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10mm (&lt;1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Approximately 1-8.2 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With an Objective Response (Partial Response + Complete Response)</title>
          <description>Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10mm (&lt;1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <units>Proportion of 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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Complete Response</title>
              <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>Median Progression-free Survival (PFS)</title>
        <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first and was calculated using the Kaplan-Meier method.</description>
        <time_frame>From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks</time_frame>
        <population>All participants are grouped together as pre-specified in the protocol for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>All Participants</title>
            <description>All participants that received 75mg selumetinib sulfate by mouth (PO) twice daily (BID); and 75mg Selumetinib sulfate twice daily followed by 50mg twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Progression-free Survival (PFS)</title>
          <description>PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first and was calculated using the Kaplan-Meier method.</description>
          <population>All participants are grouped together as pre-specified in the protocol for this outcome measure.</population>
          <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="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="0.8" upper_limit="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib</title>
        <description>Here are the grade 3 or greater adverse events assessed by the CTCAEv5.0 probably or definitely attributable to the agent Selumetinib. Grade 3 is defined as severe or medically significant, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. Probably is defined as likely related to the agent, and Definitely is defined as clearly related to the agent.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 25 months and 6 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Probably Attributable: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib</title>
          <description>Here are the grade 3 or greater adverse events assessed by the CTCAEv5.0 probably or definitely attributable to the agent Selumetinib. Grade 3 is defined as severe or medically significant, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. Probably is defined as likely related to the agent, and Definitely is defined as clearly related to the agent.</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Probably: Grade 3 Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Probably: Grade 3 Pancreatitis</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Definitely: Grade 3 Alanine aminotransferase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Definitely: Grade 3 Dyspnea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Definitely: Grade 3 Heart failure</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Definitely: Grade 3 Hypertension</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</title>
        <description>Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
        <time_frame>Date treatment consent signed to date off study, approximately 25 months and 6 days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).</title>
          <description>Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Semi-quantitative Measurements of Connector Enhancer of the Kinase Suppressor of Ras-1 (CNKSR1)</title>
        <description>Comparisons will be done to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.</description>
        <time_frame>Up to 52 weeks</time_frame>
        <population>This outcome measure was not done because only 1 out of the 8 enrolled participants agreed to undergo biopsy while on treatment. Tumoral biopsies were not mandatory but optional for participants enrolled onto the study. Because only one biopsy specimen was obtained, on the discretion of the PI, no analysis and no comparisons were performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Semi-quantitative Measurements of Connector Enhancer of the Kinase Suppressor of Ras-1 (CNKSR1)</title>
          <description>Comparisons will be done to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.</description>
          <population>This outcome measure was not done because only 1 out of the 8 enrolled participants agreed to undergo biopsy while on treatment. Tumoral biopsies were not mandatory but optional for participants enrolled onto the study. Because only one biopsy specimen was obtained, on the discretion of the PI, no analysis and no comparisons were performed.</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>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Predictive Biomarkers for Response to Selumetinib</title>
        <description>Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be &gt; and &lt; 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in participants with cell free deoxyribonucleic acid (cfDNA) transcripts levels &gt; 2 standard deviation (SD) above the mean, participants with cfDNA transcripts levels &lt; 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.</description>
        <time_frame>Up to 52 weeks</time_frame>
        <population>Since no responses were observed in either Arm/Group, the planned correlation was not conducted for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Predictive Biomarkers for Response to Selumetinib</title>
          <description>Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be &gt; and &lt; 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in participants with cell free deoxyribonucleic acid (cfDNA) transcripts levels &gt; 2 standard deviation (SD) above the mean, participants with cfDNA transcripts levels &lt; 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.</description>
          <population>Since no responses were observed in either Arm/Group, the planned correlation was not conducted for this outcome measure.</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>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Longitudinal Biomarker Measuring Response to Treatment</title>
        <description>Circulating free deoxyribonucleic acid (cfDNA) transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded.</description>
        <time_frame>start of treatment every (q)2 weeks, up to 52 weeks</time_frame>
        <population>This outcome measure was not done because of the lack of ctDNA copy number determinations in participants on-treatment compared to pre-treatment levels in the participants whose ctDNA levels were longitudinally evaluable. No variant profiling of baseline tumoral tissues was performed.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Longitudinal Biomarker Measuring Response to Treatment</title>
          <description>Circulating free deoxyribonucleic acid (cfDNA) transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded.</description>
          <population>This outcome measure was not done because of the lack of ctDNA copy number determinations in participants on-treatment compared to pre-treatment levels in the participants whose ctDNA levels were longitudinally evaluable. No variant profiling of baseline tumoral tissues was performed.</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>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Somatic Circulating Tumor Deoxyribonucleic Acid (ctDNA) Mutation Profile and Its Correlation With Clinical Outcome</title>
        <description>The presence of mutant DNA copies and the fractional abundance of the mutant KRAS allele on circulating tumor DNA (ctDNA) in cell-free (cf) DNA isolated from plasma samples were to be determined.</description>
        <time_frame>Baseline up to 52 weeks</time_frame>
        <population>No other somatic variants in ctDNA other than the KRAS allele were analyzed because the only available droplet digital PCR (ddPCR) assay was the one for the KRAS allele. Thus, the planned analysis change in the somatic ctDNA mutation profile and its correlation with clinical outcome was not conducted.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Somatic Circulating Tumor Deoxyribonucleic Acid (ctDNA) Mutation Profile and Its Correlation With Clinical Outcome</title>
          <description>The presence of mutant DNA copies and the fractional abundance of the mutant KRAS allele on circulating tumor DNA (ctDNA) in cell-free (cf) DNA isolated from plasma samples were to be determined.</description>
          <population>No other somatic variants in ctDNA other than the KRAS allele were analyzed because the only available droplet digital PCR (ddPCR) assay was the one for the KRAS allele. Thus, the planned analysis change in the somatic ctDNA mutation profile and its correlation with clinical outcome was not conducted.</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>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA)</title>
        <description>ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined from baseline and the last KRAS value (as a single value) before the participant came off treatment.</description>
        <time_frame>Baseline and the last KRAS value before the participant came off treatment, approximately 1- 8.2 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA)</title>
          <description>ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined from baseline and the last KRAS value (as a single value) before the participant came off treatment.</description>
          <units>copies</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2584" spread="2242"/>
                    <measurement group_id="O2" value="1556" spread="480"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Last recorded value</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6607" spread="6067"/>
                    <measurement group_id="O2" value="1542" spread="586"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Percentage Change (%) of Copies KRAS Wild Type Allele</title>
        <description>Overall ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.</description>
        <time_frame>Approximately 1- 8.2 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Percentage Change (%) of Copies KRAS Wild Type Allele</title>
          <description>Overall ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.</description>
          <units>Percentage change</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="156"/>
                    <measurement group_id="O2" value="-1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA)</title>
        <description>Mean ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined at baseline and the last recorded value while on treatment.</description>
        <time_frame>Baseline and last recorded value while on treatment, approximately 1- 8.2 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA)</title>
          <description>Mean ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined at baseline and the last recorded value while on treatment.</description>
          <units>copies</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.33" spread="3.79"/>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>On Treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.33" spread="15"/>
                    <measurement group_id="O2" value="1.6" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Percentage Change of Copies KRAS Mutant Type Allele</title>
        <description>Overall ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.</description>
        <time_frame>Approximately 1- 8.2 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Percentage Change of Copies KRAS Mutant Type Allele</title>
          <description>Overall ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.</description>
          <units>Percentage change</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="210"/>
                    <measurement group_id="O2" value="NA">The percentage was not calculable because the denominator had a value of 0.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA</title>
        <description>This outcome measure is reporting the overall percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples between baseline and on-treatment.</description>
        <time_frame>Between baseline and last recorded value while on-treatment, approximately 1- 8.2 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA</title>
          <description>This outcome measure is reporting the overall percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples between baseline and on-treatment.</description>
          <units>Percentage</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.5" spread="8.7891979156235"/>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Last recorded value</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.33" spread="14.185281887302"/>
                    <measurement group_id="O2" value="8.5" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Any Percent Change in (VAF, %), of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA)</title>
        <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value while on-treatment</description>
        <time_frame>Approximately 1- 8.2 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Any Percent Change in (VAF, %), of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA)</title>
          <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value while on-treatment</description>
          <units>Percentage change</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6"/>
                    <measurement group_id="O2" value="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline</title>
        <description>Any change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).</description>
        <time_frame>Baseline and last recorded value while on-treatment, approximately 1- 8.2 months.</time_frame>
        <population>Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline</title>
          <description>Any change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).</description>
          <population>Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.</population>
          <units>Variant Allele Fraction (VAF, %) of KRAS</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Last recorded value</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="8.5" spread="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline</title>
        <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).</description>
        <time_frame>Approximately 1- 8.2 months.</time_frame>
        <population>Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline</title>
          <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).</description>
          <population>Three out of 6 participants in dose level one and two out of 2 participants in dose level 2 had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline.</population>
          <units>Percentage change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="8.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment</title>
        <description>This outcome measure is reporting the percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value after treatment in patients with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) (Mutant Fractional KRAS Abundency at baseline and after treatment (VAF %), KRAS allele at baseline &gt; 0%).</description>
        <time_frame>Baseline and last recorded value after treatment, approximately 1- 8.2 months.</time_frame>
        <population>Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline and after treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment</title>
          <description>This outcome measure is reporting the percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value after treatment in patients with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) (Mutant Fractional KRAS Abundency at baseline and after treatment (VAF %), KRAS allele at baseline &gt; 0%).</description>
          <population>Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at baseline and after treatment</population>
          <units>Percentage change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18" spread="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Last recorded value</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28" spread="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants With Detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment</title>
        <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) between baseline and last recorded value after treatment.</description>
        <time_frame>Approximately 1- 8.2 months.</time_frame>
        <population>Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
          <group group_id="O2">
            <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
            <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants With Detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment</title>
          <description>Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) between baseline and last recorded value after treatment.</description>
          <population>Two out of 6 participants in dose level one and 0 out of 2 participants in dose level 2 had detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment</population>
          <units>Percentage change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Date treatment consent signed to date off study, approximately 25 months and 6 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Dose Level 0: 75mg Selumetinib Sulfate Twice Daily</title>
          <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
        <group group_id="E2">
          <title>75mg Selumetinib Sulfate Twice Daily Follow/by 50mg TwiceDaily</title>
          <description>Participants receive 75mg selumetinib sulfate by mouth (PO) twice daily (BID) followed by 50mg twice daily. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Colonic obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gallbladder infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Bloating</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Edema trunk</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="5" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Biliary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Peritoneal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="10" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Serum amylase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Weight loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Glucose intolerance</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypercalcemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Muscle weakness trunk</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Musculoskeletal and connective tissue disorder - Other, muscle spasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Paresthesia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal and urinary disorders - Other, Dysuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Urinary tract obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Urine discoloration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Postnasal drip</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="10" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="2"/>
              </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. Udo Rudloff</name_or_title>
      <organization>National Cancer Institute</organization>
      <phone>240-760-6238</phone>
      <email>udo.rudloff@nih.gov</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/NCT03040986
org study id: NCI-2017-00118
secondary id: NCI-2017-00118
secondary id: 17C0144
secondary id: 10050
secondary id: 10050
secondary id: ZIABC011078
nct id: NCT03040986
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well selumetinib sulfate works in treating patients with
      pancreatic cancer with Kirsten rat sarcoma (KRAS) G12R mutations that has spread from where
      it started to nearby tissue or lymph nodes or other places in the body. Selumetinib sulfate
      may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:

      I. Determine the objective response rate to selumetinib sulfate (selumetinib) administered as
      75 mg orally twice daily on a continuous schedule in patients with advanced pancreas cancer
      harboring Kirsten rat sarcoma (KRAS) G12R mutations.

      SECONDARY OBJECTIVES:

      I. To determine the progression free survival of patients with locally advanced, unresectable
      and stage IV pancreas cancer treated with selumetinib monotherapy.

      II. To evaluate the safety of selumetinib in patients with advanced pancreas cancer.

      III. To determine the impact of additional genetic alterations on the response to selumetinib
      in pancreas cancer harboring KRAS G12R mutations.

      IV. To develop a clinically applicable biomarker predicting response to selumetinib in
      pancreas cancer harboring KRAS G12R mutations.

      OUTLINE:

      Patients receive selumetinib sulfate orally (PO) twice daily (BID). Treatment repeats every
      28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 2 months for 52 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of Participants With an Objective Response (Partial Response + Complete Response)
time frame: Approximately 1-8.2 months
description: Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm (<1 cm). Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
measure: Median Progression-free Survival (PFS)
time frame: From start of treatment to time of progression or death, whichever occurs first, assessed up to 52 weeks
description: PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first and was calculated using the Kaplan-Meier method.
measure: Incidence of Grade 3 or Greater Adverse Events Using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 Probably or Definitely Attributable to the Agent Selumetinib
time frame: Date treatment consent signed to date off study, approximately 25 months and 6 days.
description: Here are the grade 3 or greater adverse events assessed by the CTCAEv5.0 probably or definitely attributable to the agent Selumetinib. Grade 3 is defined as severe or medically significant, Grade 4 is life-threatening consequences, and Grade 5 is death related to adverse event. Probably is defined as likely related to the agent, and Definitely is defined as clearly related to the agent.
measure: Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0).
time frame: Date treatment consent signed to date off study, approximately 25 months and 6 days.
description: Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
measure: Semi-quantitative Measurements of Connector Enhancer of the Kinase Suppressor of Ras-1 (CNKSR1)
time frame: Up to 52 weeks
description: Comparisons will be done to estimate the differences of the expression level in pancreas cancer tissues and clinical outcome variables.
measure: Predictive Biomarkers for Response to Selumetinib
time frame: Up to 52 weeks
description: Presence of variants identified in the 50-cancer gene panel will be compared with response, presenting the results in a 2x2 table with findings reported descriptively. Pre-treatment ctDNA levels will be divided into groups to separate aberrant values from the rest. The cutoffs will be > and < 2 standard deviations of the mean, with the cutoffs applied to both ctDNA levels. Based on these groups, resulting in participants with cell free deoxyribonucleic acid (cfDNA) transcripts levels > 2 standard deviation (SD) above the mean, participants with cfDNA transcripts levels < 2 SD below the mean, and the rest in between, the categorical results will be evaluated and reported relative to response vs. non-response in a descriptive manner.
measure: Longitudinal Biomarker Measuring Response to Treatment
time frame: start of treatment every (q)2 weeks, up to 52 weeks
description: Circulating free deoxyribonucleic acid (cfDNA) transcript levels will be followed from the start of treatment every (q)2 weeks and the change to pre-treatment will be plotted for each timepoint in a spider plot format. Variant profile derived from voluntary repeat biopsies will be compared to pre-treatment variant profile and gain of variants (adjusted for similar sequencing depth) will be recorded.
measure: Change in the Somatic Circulating Tumor Deoxyribonucleic Acid (ctDNA) Mutation Profile and Its Correlation With Clinical Outcome
time frame: Baseline up to 52 weeks
description: The presence of mutant DNA copies and the fractional abundance of the mutant KRAS allele on circulating tumor DNA (ctDNA) in cell-free (cf) DNA isolated from plasma samples were to be determined.
measure: Mean Copy Number KRAS Wild Type Allele in Circulating Tumor DNA (ctDNA)
time frame: Baseline and the last KRAS value before the participant came off treatment, approximately 1- 8.2 months.
description: ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined from baseline and the last KRAS value (as a single value) before the participant came off treatment.
measure: Overall Percentage Change (%) of Copies KRAS Wild Type Allele
time frame: Approximately 1- 8.2 months.
description: Overall ctDNA copy number measurements of KRAS wild type alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.
measure: Mean Copy Number KRAS Mutant Type Allele in Circulating Tumor DNA (ctDNA)
time frame: Baseline and last recorded value while on treatment, approximately 1- 8.2 months.
description: Mean ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples was determined at baseline and the last recorded value while on treatment.
measure: Overall Percentage Change of Copies KRAS Mutant Type Allele
time frame: Approximately 1- 8.2 months.
description: Overall ctDNA copy number measurements of KRAS mutant alleles in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant at baseline and last recorded value while on-treatment.
measure: Percentage of KRAS Allele in Circulating Tumor DNA (ctDNA) That is Identified as Variant From Cell-free (cf) DNA
time frame: Between baseline and last recorded value while on-treatment, approximately 1- 8.2 months.
description: This outcome measure is reporting the overall percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples between baseline and on-treatment.
measure: Overall Any Percent Change in (VAF, %), of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA)
time frame: Approximately 1- 8.2 months.
description: Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value while on-treatment
measure: Mean Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline
time frame: Baseline and last recorded value while on-treatment, approximately 1- 8.2 months.
description: Any change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).
measure: Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants Who Had No Measurable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline
time frame: Approximately 1- 8.2 months.
description: Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and while on-treatment in patients with no Mutant Fractional KRAS Abundency at baseline (VAF %, KRAS allele at baseline = 0% ).
measure: Percentage Change of KRAS Allele in Circulating Tumor Deoxyribonucleic Acid (ctDNA) That is Identified as Variant From Cell-free (cf) DNA at Baseline and After Treatment
time frame: Baseline and last recorded value after treatment, approximately 1- 8.2 months.
description: This outcome measure is reporting the percentage of KRAS allele in circulating tumor DNA (ctDNA) that is identified as variant from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant between baseline and last recorded value after treatment in patients with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) (Mutant Fractional KRAS Abundency at baseline and after treatment (VAF %), KRAS allele at baseline > 0%).
measure: Overall Percent Change in Variant Allele Fraction (VAF, %) of KRAS in Participants With Detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) at Baseline and After Treatment
time frame: Approximately 1- 8.2 months.
description: Overall change in Variant Allele Fraction (VAF, %) of KRAS allele in circulating tumor DNA (ctDNA) from cell-free (cf) DNA isolated from plasma samples determined from a single percentage change for the group rather than a percentage change for each participant with detectable KRAS Mutant Circulating Tumor Deoxyribonucleic Acid (ctDNA) between baseline and last recorded value after treatment.
arm group label: Treatment (selumetinib sulfate)
arm group type: Experimental
description: Patients receive selumetinib sulfate by mouth (PO) twice daily (BID). Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (selumetinib sulfate)
intervention type: Drug
intervention name: Selumetinib Sulfate
description: Given by mouth (PO)
arm group label: Treatment (selumetinib sulfate)
other name: AZD-6244 Hydrogen Sulfate
other name: AZD6244 Hydrogen Sulfate
other name: AZD6244 Hydrogen Sulphate
other name: Selumetinib Sulphate
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Udo Rudloff
role: Principal Investigator
affiliation: National Cancer Institute LAO
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Pancreatic Neoplasms
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 