<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/NCT03232892</url>
  </required_header>
  <id_info>
    <org_study_id>166521</org_study_id>
    <secondary_id>NCI-2017-02295</secondary_id>
    <nct_id>NCT03232892</nct_id>
  </id_info>
  <brief_title>Trametinib in Patients With Advanced Neurofibromatosis Type 1 (NF1)-Mutant Non-small Cell Lung Cancer</brief_title>
  <official_title>Phase II Trial to Evaluate Trametinib in Patients With Advanced NF1-mutant Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>American Cancer Society, Inc.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phase II trial to evaluate trametinib in patients with locally advanced non-squamous,&#xD;
      non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with&#xD;
      progressive disease on at least one prior line of therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a phase II, single-arm, open-label, multicenter clinical trial evaluating the&#xD;
      efficacy and safety of trametinib monotherapy in patients with advanced non-squamous NSCLC&#xD;
      whose tumors non-synonymous NF1 mutations and are KRAS wildtype. Eligible patients must have&#xD;
      documented disease progression either during or after treatment with most recent therapy and&#xD;
      may not have received prior treatment with a MEK inhibitor. Patients with activating&#xD;
      alterations in EGFR, ALK, and ROS-1 must also have received appropriate TKI treatment.&#xD;
      Patients who meet eligibility criteria will receive trametinib monotherapy and followed for&#xD;
      the primary endpoint of objective response rate and additional secondary endpoints. A total&#xD;
      of 27 patients will be enrolled into the study, with the goals of obtaining 24 evaluable&#xD;
      patients. Patients may continue treatment until disease progression or up to 24 months from&#xD;
      the time of study entry or until the study is closed. All patients will be followed for 12&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Low Accrual&#xD;
  </why_stopped>
  <start_date type="Actual">February 13, 2018</start_date>
  <completion_date type="Actual">September 11, 2019</completion_date>
  <primary_completion_date type="Actual">September 11, 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>Phase 2, single-arm, open label, multicenter clinical trial.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>No masking</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>For participants receiving at least one dose of study treatment, the ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence as assessed over a 1-year period from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined. We will test the hypothesis that the ORR is greater than the null hypothesis of 10% using the Fisher's exact test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DR)</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis. The DR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) According to RECIST Version 1.1 Criteria.</measure>
    <time_frame>Up to 4 years</time_frame>
    <description>DCR will be defined as the percentage of patients who have achieved CR, PR, or SD for at least 12 weeks. The DCR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria.</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Trametinib 2.0mg PO daily</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>Trametinib 2mg, once daily, PO, 28-day cycles</description>
    <arm_group_label>Trametinib 2.0mg PO daily</arm_group_label>
    <other_name>Mekinist</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed metastatic or unresectable locally advanced,&#xD;
             non-squamous, NSCLC.&#xD;
&#xD;
          2. Documented non-synonymous somatic mutation in NF1 in any tumor specimen or cell-free&#xD;
             DNA assay by Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory.&#xD;
&#xD;
          3. Received at least one prior line of cancer therapy for the treatment of NSCLC; this&#xD;
             should include at least one of the following: platinum (carboplatin or cisplatin)&#xD;
             doublet chemotherapy (acceptable combinations include: paclitaxel, docetaxel,&#xD;
             abraxane, pemetrexed, gemcitabine, vinorelbine, or etoposide), anti-PD1/PDL1 therapy&#xD;
             (pembrolizumab, nivolumab, or atezolizumab), or appropriate targeted therapy in&#xD;
             patients with activating EGFR (osimertinib, erlotinib, gefitinib, or afatinib), ALK&#xD;
             (alectinib, crizotinib, ceritinib, brigatinib, or loralatinib), or ROS-1 (crizotininb&#xD;
             or entrectinib) alterations; therapy may be given as monotherapy or in combination&#xD;
             with other cancer therapy (e.g. bevacizumab, ipilumimab)&#xD;
&#xD;
          4. Patients with a known activating mutation in epidermal growth factor receptor (EGFR)&#xD;
             (Exon 19 deletion, G719A, S768I, V769L, T790M, L833F, L858R, L861Q), must have&#xD;
             progressed or been intolerant to treatment with a first-line EGFR tyrosine kinase&#xD;
             inhibitor (TKI) (erlotinib, afatinib, or gefitinib). Patients whose tumors were found&#xD;
             to have an EGFR T790M mutation must also have progressed or been intolerable to&#xD;
             treatment with osimertinib.&#xD;
&#xD;
          5. Patients with a known Anaplastic lymphoma kinase (ALK)-rearrangement must have&#xD;
             progressed or been intolerant to treatment with at least one ALK TKI: crizotinib&#xD;
             ceritinib, alectinib,brigatinib, or loralatinib&#xD;
&#xD;
          6. Patients with a known ROS-1-rearrangement must have progressed or been intolerant to&#xD;
             treatment with crizotinib or entrectinib&#xD;
&#xD;
          7. Patients with PDL1 level of &gt;= 50%, who do not have an ALK-rearrangement or&#xD;
             EGFR-mutation, must have progressed or been intolerant to treatment with anti-PD1/PDL1&#xD;
             therapy (pembrolizumab, nivolumab, or atezolizumab)&#xD;
&#xD;
          8. Documented disease progression or intolerance to treatment either during or after&#xD;
             treatment with most recent therapy.&#xD;
&#xD;
          9. Willingness to undergo research biopsy.&#xD;
&#xD;
         10. Measurable disease defined by RECIST 1.1 criteria.&#xD;
&#xD;
         11. Life expectancy of at least 3 months.&#xD;
&#xD;
         12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
&#xD;
         13. Age ≥ 18 years.&#xD;
&#xD;
         14. Resolution of all acute toxic effects of prior chemotherapy, immunotherapy,&#xD;
             radiotherapy or surgical procedures to National Cancer Institute (NCI) Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) Version 4.03 grade 1.&#xD;
&#xD;
         15. Adequate baseline organ function defined as follows:&#xD;
&#xD;
             Hematologic:&#xD;
&#xD;
               -  Absolute neutrophil count: ≥ 1.2 x 10^9/L&#xD;
&#xD;
               -  Hemoglobin: ≥ 9 g/dL&#xD;
&#xD;
               -  Platelets: ≥ 100 x 10^9/L&#xD;
&#xD;
               -  PT/INR and PTT: ≤ 1.5 x upper limit of normal (ULN)&#xD;
&#xD;
             Hepatic:&#xD;
&#xD;
               -  Albumin: ≥ 2.5 g/dL&#xD;
&#xD;
               -  Total bilirubin: ≤ 1.5 x ULN&#xD;
&#xD;
               -  AST and ALT: ≤ 2.5 x ULN&#xD;
&#xD;
             Renal:&#xD;
&#xD;
               -  Creatine: ≤ 1.5 ULN or&#xD;
&#xD;
               -  Calculated creatinine clearance (calculated by the Cockcroft-Gault formula): ≥ 50&#xD;
                  mL/min&#xD;
&#xD;
             Cardiac:&#xD;
&#xD;
             - Left Ventricular Ejection Fraction (LVEF): ≥ lower limit of normal (LLN) by&#xD;
             echocardiogram (ECHO) or multiple-gated acquisition (MUGA)&#xD;
&#xD;
         16. Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
             within 3 days prior to study enrollment. The effects of trametinib on the developing&#xD;
             human fetus are unknown. For this reason and because animal studies with trametinib&#xD;
             have shown reproductive toxicity, women of child-bearing potential and men must agree&#xD;
             to use effective methods of contraception (hormonal or barrier method of birth&#xD;
             control) prior to study entry, for the duration of study participation, and for 4&#xD;
             months following discontinuation of trametinib. Should a woman become pregnant or&#xD;
             suspect she is pregnant while she or her partner is participating in this study, she&#xD;
             should inform her treating physician immediately. Men treated or enrolled on this&#xD;
             protocol must also agree to use adequate contraception prior to the study, for the&#xD;
             duration of study participation, and 4 months after completion of study drug&#xD;
             administration.&#xD;
&#xD;
         17. Able to swallow and retain orally administered medication and does not have any&#xD;
             clinically significant gastrointestinal abnormalities that may alter absorption such&#xD;
             as malabsorption syndrome or major resection of the stomach or bowels.&#xD;
&#xD;
         18. All prior treatment- related toxicities must be CTCAE (Version 4.03) ≤ Grade 1 (except&#xD;
             alopecia) at the time of randomization&#xD;
&#xD;
         19. Ability to understand a written informed consent document, and the willingness to sign&#xD;
             it.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known mutation in KRAS at position G12, G13, or Q61.&#xD;
&#xD;
          2. Symptomatic or untreated leptomeningeal or brain metastases or spinal cord&#xD;
             compression. Treated brain metastases are allowed as long as they are stable for at&#xD;
             least 28 days post-treatment.&#xD;
&#xD;
          3. Pregnant women are excluded from this study; breastfeeding should be discontinued if&#xD;
             the mother is treated with trametinib . Because there is an unknown but potential risk&#xD;
             for adverse events in nursing infants secondary to treatment of the mother with&#xD;
             trametinib, breastfeeding should be discontinued if the mother is treated with&#xD;
             trametinib.&#xD;
&#xD;
          4. History of another malignancy. Exception: Subjects who have been disease-free for 3&#xD;
             years, or subjects with a history of completely resected non-melanoma skin cancer&#xD;
             and/or subjects with indolent second malignancies are eligible.&#xD;
&#xD;
          5. Any serious and/or unstable pre-existing medical disorder (aside from malignancy&#xD;
             exception above), psychiatric disorder, or other conditions that could interfere with&#xD;
             subject's safety, obtaining informed consent or compliance to the study procedures.&#xD;
&#xD;
          6. The subject has received cytotoxic chemotherapy, molecular targeted therapy, or&#xD;
             immunotherapy within 21 days before the first dose of study drug (trametinib).&#xD;
&#xD;
          7. Prior treatment with MEK inhibitor.&#xD;
&#xD;
          8. History of interstitial lung disease or pneumonitis.&#xD;
&#xD;
          9. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs&#xD;
             chemically related to study drug, or excipients or to dimethyl sulfoxide (DMSO).&#xD;
&#xD;
         10. Any major surgery, extensive radiotherapy, chemotherapy with delayed toxicity,&#xD;
             biologic therapy, or immunotherapy within 21 days prior to study enrollment and/or&#xD;
             daily or weekly chemotherapy without the potential for delayed toxicity within 14 days&#xD;
             prior to study enrollment.&#xD;
&#xD;
         11. History of retinal vein occlusion (RVO).&#xD;
&#xD;
         12. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C&#xD;
             Virus (HCV) infection (subjects with laboratory evidence of cleared HBV and HCV&#xD;
             infection will be permitted).&#xD;
&#xD;
         13. History or evidence of cardiovascular risk including any of the following:&#xD;
&#xD;
               -  LVEF &lt; LLN&#xD;
&#xD;
               -  A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480&#xD;
                  msec;&#xD;
&#xD;
               -  History or evidence of current clinically significant uncontrolled arrhythmias.&#xD;
&#xD;
               -  Clarification: Subjects with atrial fibrillation controlled (defined as not&#xD;
                  requiring change in cardiac drug dosing, emergency room visit, or hospital&#xD;
                  admission) for &gt; 30 days prior to dosing are eligible.&#xD;
&#xD;
               -  History of acute coronary syndromes (including myocardial infarction and unstable&#xD;
                  angina), coronary angioplasty, or stenting within 6 months prior to study&#xD;
                  enrollment.&#xD;
&#xD;
               -  History or evidence of current ≥ Class II congestive heart failure as defined by&#xD;
                  New York Heart Association (NYHA).&#xD;
&#xD;
               -  Treatment refractory hypertension defined as a blood pressure of systolic &gt; 140&#xD;
                  mmHg and/or diastolic &gt; 90 mm Hg which cannot be controlled by anti-hypertensive&#xD;
                  therapy;&#xD;
&#xD;
               -  Patients with intra-cardiac defibrillators.&#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>Collin Blakely, MD, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>July 14, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>November 13, 2019</results_first_submitted>
  <results_first_submitted_qc>November 13, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">December 3, 2019</results_first_posted>
  <last_update_submitted>November 13, 2019</last_update_submitted>
  <last_update_submitted_qc>November 13, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">December 3, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>NSCLC</keyword>
  <keyword>NF-1 mutant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trametinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Will not be shared</ipd_description>
  </patient_data>
  <provided_document_section>
    <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>April 9, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03232892/ICF_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03232892/Prot_SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Trametinib 2.0mg PO Daily</title>
          <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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>The study was closed due to low accrual with a total of 1 participant enrolled on this protocol.</population>
      <group_list>
        <group group_id="B1">
          <title>Trametinib 2.0mg PO Daily</title>
          <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>60-69 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_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="1"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>For participants receiving at least one dose of study treatment, the ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence as assessed over a 1-year period from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined. We will test the hypothesis that the ORR is greater than the null hypothesis of 10% using the Fisher's exact test.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Trametinib 2.0mg PO Daily</title>
            <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>For participants receiving at least one dose of study treatment, the ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence as assessed over a 1-year period from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined. We will test the hypothesis that the ORR is greater than the null hypothesis of 10% using the Fisher's exact test.</description>
          <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DR)</title>
        <description>The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis. The DR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).</description>
        <time_frame>Up to 4 years</time_frame>
        <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Trametinib 2.0mg PO Daily</title>
            <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DR)</title>
          <description>The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis. The DR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).</description>
          <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR) According to RECIST Version 1.1 Criteria.</title>
        <description>DCR will be defined as the percentage of patients who have achieved CR, PR, or SD for at least 12 weeks. The DCR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).</description>
        <time_frame>Up to 4 years</time_frame>
        <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Trametinib 2.0mg PO Daily</title>
            <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR) According to RECIST Version 1.1 Criteria.</title>
          <description>DCR will be defined as the percentage of patients who have achieved CR, PR, or SD for at least 12 weeks. The DCR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).</description>
          <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria.</title>
        <description>PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Trametinib 2.0mg PO Daily</title>
            <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria.</title>
          <description>PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.</description>
          <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.</description>
        <time_frame>Up to 1 year</time_frame>
        <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Trametinib 2.0mg PO Daily</title>
            <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.</description>
          <population>The single participant did not allow for a sufficient data collection of endpoint analysis</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 1 year</time_frame>
      <desc>The safety population will consist of all subjects who receive any amount of study treatment which for this protocol is a total of 1 participant. Adverse event terms recorded on the CRFs were be mapped to preferred terms using the Medical Dictionary for Regulatory Activities (MedDRA). Seriousness, severity grade and relationship to study treatment will be assessed by the investigator. Severity grade will be defined by the National Cancer Institute (NCI) CTCAE v4.03</desc>
      <group_list>
        <group group_id="E1">
          <title>Trametinib 2.0mg PO Daily</title>
          <description>Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.&#xD;
Trametinib: Trametinib 2mg, once daily, PO, 28-day cycles</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.0)</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="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>shortness of breath</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>hypoxic respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (19.0)</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="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </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>
    <limitations_and_caveats>There was only one participant enrolled on this trial and the study was terminated early due to low accrual. No analyses were conducted on any of the samples collected as there was insufficient material available for analysis</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr. Collin Blakely, MD PhD.</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>(415) 502-6959</phone>
      <email>Collin.Blakely@ucsf.edu</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/NCT03232892
org study id: 166521
secondary id: NCI-2017-02295
nct id: NCT03232892
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Phase II trial to evaluate trametinib in patients with locally advanced non-squamous,
      non-small cell lung cancer (NSCLC) whose tumors harbor a non-synonymous NF-1 mutation, with
      progressive disease on at least one prior line of therapy.
This is a phase II, single-arm, open-label, multicenter clinical trial evaluating the
      efficacy and safety of trametinib monotherapy in patients with advanced non-squamous NSCLC
      whose tumors non-synonymous NF1 mutations and are KRAS wildtype. Eligible patients must have
      documented disease progression either during or after treatment with most recent therapy and
      may not have received prior treatment with a MEK inhibitor. Patients with activating
      alterations in EGFR, ALK, and ROS-1 must also have received appropriate TKI treatment.
      Patients who meet eligibility criteria will receive trametinib monotherapy and followed for
      the primary endpoint of objective response rate and additional secondary endpoints. A total
      of 27 patients will be enrolled into the study, with the goals of obtaining 24 evaluable
      patients. Patients may continue treatment until disease progression or up to 24 months from
      the time of study entry or until the study is closed. All patients will be followed for 12
      months.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Phase 2, single-arm, open label, multicenter clinical trial.
primary purpose: Treatment
masking: None (Open Label)
masking description: No masking
measure: Objective Response Rate (ORR)
time frame: Up to 1 year
description: For participants receiving at least one dose of study treatment, the ORR is defined as the best overall response recorded from the start of the treatment until disease progression or recurrence as assessed over a 1-year period from the start of treatment. The frequency and percentages of patients with a best overall response rate of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) will be determined. We will test the hypothesis that the ORR is greater than the null hypothesis of 10% using the Fisher's exact test.
measure: Duration of Response (DR)
time frame: Up to 4 years
description: The DR for Complete Response (CR) and Partial Response (PR) will be measured from the date that the best response is first recorded until the date that PD is documented. For patients who continue treatment post progression, the date of Disease Progression (PD) documentation will be used for analysis. The DR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
measure: Disease Control Rate (DCR) According to RECIST Version 1.1 Criteria.
time frame: Up to 4 years
description: DCR will be defined as the percentage of patients who have achieved CR, PR, or SD for at least 12 weeks. The DCR will be summarized using descriptive statistics (N, mean, standard deviation, minimum, and maximum).
measure: Progression Free Survival (PFS) According to RECIST Version 1.1 Criteria.
time frame: Up to 1 year
description: PFS will be calculated as 1+ the number of days from the first dose of study drugs to documented radiographic progression or death due to any cause over a period of 1 year. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. For patients who continue treatment post-progression, the date of radiographic progression will be used for PFS analysis. The Kaplan-Meier analysis will be used to calculate the median PFS with 95% confidence interval.
measure: Overall Survival (OS)
time frame: Up to 1 year
description: OS will be calculated as 1+ the number of days from the first dose of study drugs to death due to any cause over a period of 1 year. The Kaplan-Meier analysis will be used to calculate the median OS with 95% confidence interval.
arm group label: Trametinib 2.0mg PO daily
arm group type: Experimental
description: Trametinib 2.0mg PO daily in 28-day cycles. A maximum of two trametinib dose level reductions are allowed (1.5mg and 1mg) in the case of adverse reactions.
intervention type: Drug
intervention name: Trametinib
description: Trametinib 2mg, once daily, PO, 28-day cycles
arm group label: Trametinib 2.0mg PO daily
other name: Mekinist
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Collin Blakely, MD, PhD
role: Study Chair
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Trametinib
sharing ipd: No
ipd description: Will not be shared
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: There was only one participant enrolled on this trial and the study was terminated early due to low accrual. No analyses were conducted on any of the samples collected as there was insufficient material available for analysis
point of contact: 