<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/NCT03287947</url>
  </required_header>
  <id_info>
    <org_study_id>LCI-GI-APX-NIN-001</org_study_id>
    <secondary_id>00021617</secondary_id>
    <nct_id>NCT03287947</nct_id>
  </id_info>
  <brief_title>LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma</brief_title>
  <official_title>LCI-GI-APX-NIN-001: Nintedanib in Metastatic Appendiceal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Wake Forest University Health Sciences</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this trial is to evaluate the disease control rate of nintedanib in subjects&#xD;
      with metastatic appendiceal cancer for whom initial fluoropyrimidine-based chemotherapy has&#xD;
      failed. Based on previous studies, the anticancer activity of nintedanib in lung and ovarian&#xD;
      cancer trials, along with the similarities between appendiceal and colorectal cancer and&#xD;
      potentially ovarian cancer, warrant additional investigation for the optimal treatment of&#xD;
      metastatic appendiceal carcinomas.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary study objective is to evaluate the disease control rate. The secondary study&#xD;
      objectives are to evaluate safety and toxicity, objective response rate, overall and 6-month&#xD;
      progression free survival, and overall survival. Exploratory study objectives include&#xD;
      evaluation of serum and ascites VEGF, hypertension, and paracentesis frequency in subjects&#xD;
      with ascites at study entry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">November 10, 2017</start_date>
  <completion_date type="Actual">October 27, 2019</completion_date>
  <primary_completion_date type="Actual">September 3, 2019</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single arm phase 2 study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Disease Control Rate</measure>
    <time_frame>From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.</time_frame>
    <description>The disease control rate is the proportion of those subjects with complete response, partial response, or stable disease, as defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Complete Response (CR), Disappearance of all target and non-target lesions, any pathological lymph nodes reduced in short axis to &lt;10 mm; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor PD; Disease Control Rate (DCR) = CR + PR + SD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.</time_frame>
    <description>Overall survival was defined as the duration from the start of nintedanib treatment to the date of death from any cause; subjects who are alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive. Median overall survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of overall survival was performed due to low accrual.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>From date of first dose of study treatment to the date of progressive disease or death from any cause, whichever occurred first, assessed up to 7.5 months.</time_frame>
    <description>Progression-free survival was defined as the duration from the start of nintedanib treatment to the first occurrence of either progressive disease or death; disease progression was objectively determined per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) or subjectively determined by the investigator. Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Progressive Disease (PD), &gt;= 20% increase in the sum of the longest diameter of target lesions (at least 5 mm), or a measurable increase or progression in a non-target lesion, or the appearance of new lesions. Median progression-free survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of progression-free survival was performed due to low accrual.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.</measure>
    <time_frame>From the first dose of study drug to the last dose, assessed up to 7.5 months.</time_frame>
    <description>The average daily dose of nintedanib is calculated as the total cumulative dose (in mg) of nintedanib administered divided by the number of 28-day cycles on nintedanib treatment. Prescribed daily dose of nintedanib is 400 mg.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Appendix Cancer</condition>
  <arm_group>
    <arm_group_label>A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Nintedanib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nintedanib</intervention_name>
    <description>Oral nintedanib, taken twice daily</description>
    <arm_group_label>A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
        Subjects must meet all of the following criteria:&#xD;
&#xD;
          1. Age at least 18 years old&#xD;
&#xD;
          2. Histologically confirmed appendiceal carcinoma stage IV&#xD;
&#xD;
          3. Failure of initial fluoropyrimidine -based chemotherapy. Failure is defined as&#xD;
             progression on or within 6 months of last day of therapy or intolerance of initial&#xD;
             fluoropyrimidine-based chemotherapy.&#xD;
&#xD;
          4. Life expectancy at least 3 months&#xD;
&#xD;
          5. ECOG performance status score 0-2&#xD;
&#xD;
          6. Presence of measurable and/or evaluable, non-measurable disease according to RECIST&#xD;
             1.1 criteria&#xD;
&#xD;
          7. Written informed consent signed and dated by subject or Legally Authorized&#xD;
             Representative (LAR) prior to admission to the study in accordance with ICH-GCP&#xD;
             guidelines and to the local legislation.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Subjects must not meet any of the following criteria.&#xD;
&#xD;
          1. Prior treatment with nintedanib or any other VEGFR inhibitor&#xD;
&#xD;
          2. Known hypersensitivity to peanut or soya or to contrast media. History of&#xD;
             hypersensitivity to contrast media is allowed if the subject is able to tolerate&#xD;
             contrast media with pre-medication.&#xD;
&#xD;
          3. Chemo-, hormone-, radio-(except for brain and extremities) or immunotherapy, or&#xD;
             therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the past&#xD;
             4 weeks prior to treatment with the trial drug.&#xD;
&#xD;
          4. Radiotherapy to any target lesion within the past 3 months prior to baseline imaging&#xD;
             when that target lesion is the only target lesion identified on baseline imaging,&#xD;
             unless it has subsequently grown.&#xD;
&#xD;
          5. Persistence of clinically relevant therapy related toxicity from previous chemo and/or&#xD;
             radiotherapy as determined by the investigator.&#xD;
&#xD;
          6. Active brain metastases (e.g. stable for &lt;4 weeks, no adequate previous treatment with&#xD;
             radiotherapy, symptomatic, requiring treatment with anti-convulsants; dexamethasone&#xD;
             therapy will be allowed if administered as stable dose for at least one month) or&#xD;
             leptomeningeal disease.&#xD;
&#xD;
          7. Radiographic evidence of cavitary or necrotic tumors.&#xD;
&#xD;
          8. Tumors with radiographic evidence (CT or MRI) of local invasion of major blood&#xD;
             vessels.&#xD;
&#xD;
          9. Anti-neoplastic treatment for appendiceal cancer, with other investigational drugs or&#xD;
             treatment in another clinical trial within 30 days before start of study treatment.&#xD;
&#xD;
         10. Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose&#xD;
             heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous&#xD;
             devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic&#xD;
             acid less than or equal to 325mg per day).&#xD;
&#xD;
         11. Major injuries and/or surgery within the past 4 weeks prior to start of study&#xD;
             treatment, incomplete wound healing or planned surgery during the on-treatment study&#xD;
             period.&#xD;
&#xD;
         12. History of clinically significant hemorrhagic or thromboembolic event in the past 6&#xD;
             months prior to consent.&#xD;
&#xD;
         13. Known inherited predisposition to bleeding or thrombosis.&#xD;
&#xD;
         14. Significant cardiovascular diseases (i.e. uncontrolled hypertension, unstable angina,&#xD;
             history of infarction, congestive heart failure &gt; NYHA II, serious cardiac arrhythmia,&#xD;
             pericardial effusion) within the past 12 months prior to start of study treatment.&#xD;
&#xD;
         15. Proteinuria CTCAE grade 2 or greater.&#xD;
&#xD;
         16. Creatinine &gt; 1.5x ULN or GFR &lt; 45 ml/min.&#xD;
&#xD;
         17. Hepatic function: total bilirubin above normal limits; ALT or AST &gt; 1.5x ULN in&#xD;
             subjects without liver metastasis. For subjects with liver metastasis: total bilirubin&#xD;
             above normal limits; ALT or AST &gt; 2.5x ULN.&#xD;
&#xD;
         18. Coagulation parameters: International normalised ratio (INR) &gt; 2x ULN, prothrombin&#xD;
             time (PT) and partial thromboplastin time (PTT) &gt; or equal to 1.5x ULN.&#xD;
&#xD;
         19. Absolute neutrophil count (ANC) &lt; 1500/ml, platelets &lt; 100000/ml, Hemoglobin &lt; 9.0&#xD;
             g/dl.&#xD;
&#xD;
         20. Other malignancies at the time of signing the informed consent other than basal cell&#xD;
             skin cancer or carcinoma in situ of the cervix.&#xD;
&#xD;
         21. Active serious infections if requiring systemic antibiotic or antimicrobial therapy.&#xD;
&#xD;
         22. Active or chronic hepatitis C and/or B infection.&#xD;
&#xD;
         23. Gastrointestinal disorders (like chronic diarrhea) or abnormalities that would&#xD;
             interfere with absorption of the study drug. Subjects with this disorder may be&#xD;
             allowed if able to tolerate anti-diarrheal medications like loperamide.&#xD;
&#xD;
         24. Serious illness or concomitant non-oncological disease such as neurologic,&#xD;
             psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or&#xD;
             laboratory abnormality that may increase the risk associated with study participation&#xD;
             or study drug administration and in the judgment of the investigator would make the&#xD;
             subject inappropriate for entry into the study.&#xD;
&#xD;
         25. Sexually active women of child-bearing potential and men who are sexually active with&#xD;
             women of child-bearing potential and unwilling to use at least 2 medically acceptable&#xD;
             methods of contraception (e.g. such as implants, injectables, combined oral&#xD;
             contraceptives, some intrauterine devices or vasectomized partner for participating&#xD;
             females, condoms for participating males) during the trial and for at least three&#xD;
             months after end of active therapy. Female subjects will be considered of&#xD;
             child-bearing potential unless surgically sterilized by hysterectomy or bilateral&#xD;
             tubal/salpingectomy, or post-menopausal for at least 2 years.&#xD;
&#xD;
         26. Pregnancy or breast feeding; female participants of child-bearing potential must have&#xD;
             a negative pregnancy test (B-HCG test in urine or serum) before commencing study&#xD;
             treatment.&#xD;
&#xD;
        aa. Psychological, familial, sociological, or geographical factors potentially hampering&#xD;
        compliance with the study protocol and follow-up schedule per the investigator.&#xD;
&#xD;
        bb. Alcohol or drug abuse which in the determination of the investigator would interfere&#xD;
        with trial participation.&#xD;
&#xD;
        cc. Significant weight loss (&gt; 10% of baseline weight) within past 2 months prior to&#xD;
        consenting for the trial. Removal of ascites should not be calculated as weight loss.&#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>Jimmy J Hwang, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Wake Forest University Health Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Levine Cancer Institute</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>July 31, 2017</study_first_submitted>
  <study_first_submitted_qc>September 18, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 19, 2017</study_first_posted>
  <results_first_submitted>October 26, 2020</results_first_submitted>
  <results_first_submitted_qc>June 15, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 16, 2021</results_first_posted>
  <last_update_submitted>August 5, 2022</last_update_submitted>
  <last_update_submitted_qc>August 5, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2022</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>Appendiceal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nintedanib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03287947/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>October 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/47/NCT03287947/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nintedanib</title>
          <description>Participants received 200 mg oral nintedanib, taken twice daily.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5">Five subjects were enrolled to the study.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5">All subjects enrolled discontinued treatment and are now off study.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Five subjects enrolled to the study at their initiations of nintedanib therapy.</population>
      <group_list>
        <group group_id="B1">
          <title>Nintedanib</title>
          <description>Subjects received 200 mg oral nintedanib, taken twice daily.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="62.8" spread="15.8"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ascites present at baseline</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Disease Control Rate</title>
        <description>The disease control rate is the proportion of those subjects with complete response, partial response, or stable disease, as defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Complete Response (CR), Disappearance of all target and non-target lesions, any pathological lymph nodes reduced in short axis to &lt;10 mm; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor PD; Disease Control Rate (DCR) = CR + PR + SD.</description>
        <time_frame>From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.</time_frame>
        <population>Subjects enrolled to the study at their initiations of nintedanib therapy and had measurable disease at baseline; four of five enrolled subjects had measurable disease at baseline.</population>
        <group_list>
          <group group_id="O1">
            <title>Nintedanib</title>
            <description>Subjects received 200 mg oral nintedanib, taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate</title>
          <description>The disease control rate is the proportion of those subjects with complete response, partial response, or stable disease, as defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Complete Response (CR), Disappearance of all target and non-target lesions, any pathological lymph nodes reduced in short axis to &lt;10 mm; Partial Response (PR), &gt;=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor PD; Disease Control Rate (DCR) = CR + PR + SD.</description>
          <population>Subjects enrolled to the study at their initiations of nintedanib therapy and had measurable disease at baseline; four of five enrolled subjects had measurable disease at baseline.</population>
          <units>Proportion of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".25" lower_limit=".0064" upper_limit=".8058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall survival was defined as the duration from the start of nintedanib treatment to the date of death from any cause; subjects who are alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive. Median overall survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of overall survival was performed due to low accrual.</description>
        <time_frame>From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.</time_frame>
        <population>All five enrolled subjects are evaluable for the analysis of overall survival.</population>
        <group_list>
          <group group_id="O1">
            <title>Nintedanib</title>
            <description>Subjects received 200 mg oral nintedanib, taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall survival was defined as the duration from the start of nintedanib treatment to the date of death from any cause; subjects who are alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive. Median overall survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of overall survival was performed due to low accrual.</description>
          <population>All five enrolled subjects are evaluable for the analysis of overall survival.</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.62" lower_limit="0.78" upper_limit="14.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Progression-free survival was defined as the duration from the start of nintedanib treatment to the first occurrence of either progressive disease or death; disease progression was objectively determined per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) or subjectively determined by the investigator. Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Progressive Disease (PD), &gt;= 20% increase in the sum of the longest diameter of target lesions (at least 5 mm), or a measurable increase or progression in a non-target lesion, or the appearance of new lesions. Median progression-free survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of progression-free survival was performed due to low accrual.</description>
        <time_frame>From date of first dose of study treatment to the date of progressive disease or death from any cause, whichever occurred first, assessed up to 7.5 months.</time_frame>
        <population>All five enrolled subjects are evaluable for the analysis of progression-free survival.</population>
        <group_list>
          <group group_id="O1">
            <title>Nintedanib</title>
            <description>Subjects received 200 mg oral nintedanib, taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Progression-free survival was defined as the duration from the start of nintedanib treatment to the first occurrence of either progressive disease or death; disease progression was objectively determined per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) or subjectively determined by the investigator. Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Progressive Disease (PD), &gt;= 20% increase in the sum of the longest diameter of target lesions (at least 5 mm), or a measurable increase or progression in a non-target lesion, or the appearance of new lesions. Median progression-free survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of progression-free survival was performed due to low accrual.</description>
          <population>All five enrolled subjects are evaluable for the analysis of progression-free survival.</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="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.34" lower_limit="0.75" upper_limit="7.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.</title>
        <description>The average daily dose of nintedanib is calculated as the total cumulative dose (in mg) of nintedanib administered divided by the number of 28-day cycles on nintedanib treatment. Prescribed daily dose of nintedanib is 400 mg.</description>
        <time_frame>From the first dose of study drug to the last dose, assessed up to 7.5 months.</time_frame>
        <population>Enrolled subjects returning bottles for drug accountability are included in the reporting of average daily dose of nintedanib.</population>
        <group_list>
          <group group_id="O1">
            <title>Nintedanib</title>
            <description>Subjects received 200 mg oral nintedanib, taken twice daily.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.</title>
          <description>The average daily dose of nintedanib is calculated as the total cumulative dose (in mg) of nintedanib administered divided by the number of 28-day cycles on nintedanib treatment. Prescribed daily dose of nintedanib is 400 mg.</description>
          <population>Enrolled subjects returning bottles for drug accountability are included in the reporting of average daily dose of nintedanib.</population>
          <units>mg per cycle day</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_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="350.4" spread="48.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for subjects from enrollment until 30 days after last dose of study drug, assessed up to 8.5 months. All-Cause Mortality data was collected from enrollment until death, assessed up to 14.5 months.</time_frame>
      <desc>The attribution and severity of adverse events were classified and recorded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.</desc>
      <group_list>
        <group group_id="E1">
          <title>Nintedanib</title>
          <description>Subjects received 200 mg oral nintedanib, taken twice daily.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Death NOS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Hypokalemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Scalp pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Danielle M Boselli</name_or_title>
      <organization>Atrium Health/Levine Cancer Institute, Department of Cancer Biostatistics</organization>
      <phone>12017903385</phone>
      <email>Danielle.Boselli@AtriumHealth.org</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03287947
org study id: LCI-GI-APX-NIN-001
secondary id: 00021617
nct id: NCT03287947
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this trial is to evaluate the disease control rate of nintedanib in subjects
      with metastatic appendiceal cancer for whom initial fluoropyrimidine-based chemotherapy has
      failed. Based on previous studies, the anticancer activity of nintedanib in lung and ovarian
      cancer trials, along with the similarities between appendiceal and colorectal cancer and
      potentially ovarian cancer, warrant additional investigation for the optimal treatment of
      metastatic appendiceal carcinomas.
The primary study objective is to evaluate the disease control rate. The secondary study
      objectives are to evaluate safety and toxicity, objective response rate, overall and 6-month
      progression free survival, and overall survival. Exploratory study objectives include
      evaluation of serum and ascites VEGF, hypertension, and paracentesis frequency in subjects
      with ascites at study entry.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single arm phase 2 study.
primary purpose: Treatment
masking: None (Open Label)
measure: Disease Control Rate
time frame: From first dose of study drug to date of progression as determined by RECIST 1.1, assessed up to 7.5 months.
description: The disease control rate is the proportion of those subjects with complete response, partial response, or stable disease, as defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Complete Response (CR), Disappearance of all target and non-target lesions, any pathological lymph nodes reduced in short axis to <10 mm; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor PD; Disease Control Rate (DCR) = CR + PR + SD.
measure: Overall Survival
time frame: From date of first dose of study treatment to the date of death from any cause, assessed up to 14.5 months.
description: Overall survival was defined as the duration from the start of nintedanib treatment to the date of death from any cause; subjects who are alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive. Median overall survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of overall survival was performed due to low accrual.
measure: Progression-free Survival
time frame: From date of first dose of study treatment to the date of progressive disease or death from any cause, whichever occurred first, assessed up to 7.5 months.
description: Progression-free survival was defined as the duration from the start of nintedanib treatment to the first occurrence of either progressive disease or death; disease progression was objectively determined per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1) or subjectively determined by the investigator. Per RECIST 1.1 criteria for target lesions assessed by radiologic evaluation of CT and tumor measurements: Progressive Disease (PD), >= 20% increase in the sum of the longest diameter of target lesions (at least 5 mm), or a measurable increase or progression in a non-target lesion, or the appearance of new lesions. Median progression-free survival was estimated using Kaplan-Meier methods. No formal comparative statistical analysis of progression-free survival was performed due to low accrual.
measure: Treatment Administration of Nintedanib, as Measured by Average Daily Dose of Nintedanib.
time frame: From the first dose of study drug to the last dose, assessed up to 7.5 months.
description: The average daily dose of nintedanib is calculated as the total cumulative dose (in mg) of nintedanib administered divided by the number of 28-day cycles on nintedanib treatment. Prescribed daily dose of nintedanib is 400 mg.
arm group label: A
arm group type: Experimental
description: Nintedanib
intervention type: Drug
intervention name: nintedanib
description: Oral nintedanib, taken twice daily
arm group label: A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jimmy J Hwang, MD
role: Principal Investigator
affiliation: Wake Forest University Health Sciences
facility: 
country: United States
responsible party type: Sponsor
mesh term: Appendiceal Neoplasms
mesh term: Nintedanib
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 