<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/NCT04439357</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-03436</org_study_id>
    <secondary_id>NCI-2020-03436</secondary_id>
    <secondary_id>EAY131-S2</secondary_id>
    <secondary_id>EAY131-S2</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <secondary_id>U24CA196172</secondary_id>
    <nct_id>NCT04439357</nct_id>
  </id_info>
  <brief_title>Testing Trametinib as a Potential Targeted Treatment in Cancers With GNAQ or GNA11 Genetic Changes (MATCH-Subprotocol S2)</brief_title>
  <official_title>MATCH Treatment Subprotocol S2: Phase II Study of Trametinib in Patients With Tumors With GNAQ or GNA11 Mutations</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II MATCH treatment trial identifies the effects of trametinib in patients whose&#xD;
      cancer has genetic changes called GNAQ or GNA11 mutations. Trametinib may block proteins&#xD;
      called MEK1 and MEK2, which may be needed for cancer cell growth when GNAQ or GNA11 mutations&#xD;
      are present. Researchers hope to learn if trametinib will shrink this type of cancer or stop&#xD;
      its growth.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To evaluate the proportion of patients with objective response (OR) to targeted study&#xD;
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment&#xD;
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple&#xD;
      myeloma.&#xD;
&#xD;
      II. To evaluate time until death or disease progression. III. To identify potential&#xD;
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or&#xD;
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and&#xD;
      imaging-based assessment platforms.&#xD;
&#xD;
      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes&#xD;
      from pre- through post-therapy imaging can predict objective response and progression free&#xD;
      survival and to evaluate the association between pre-treatment radiomic phenotypes and&#xD;
      targeted gene mutation patterns of tumor biopsy specimens.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive trametinib dimethyl sulfoxide (trametinib) orally (PO) once daily (QD) on&#xD;
      days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable&#xD;
      toxicity.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 3 months if less than 2&#xD;
      years from study entry, and then every 6 months for year 3 from study entry.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 25, 2016</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Actual">September 1, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
    <description>Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>6-month Progression-free Survival (PFS) Rate</measure>
    <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined</time_frame>
    <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
    <description>PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">4</enrollment>
  <condition>Advanced Lymphoma</condition>
  <condition>Advanced Malignant Solid Neoplasm</condition>
  <condition>Hematopoietic and Lymphoid Cell Neoplasm</condition>
  <condition>Refractory Lymphoma</condition>
  <condition>Refractory Malignant Solid Neoplasm</condition>
  <condition>Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Treatment (trametinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive trametinib dimethyl sulfoxide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib Dimethyl Sulfoxide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (trametinib)</arm_group_label>
    <other_name>Mekinist</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have met applicable eligibility criteria in the Master MATCH Protocol&#xD;
             prior to registration to treatment subprotocol&#xD;
&#xD;
          -  Patients must have GNAQ or GNA11 mutations, or another aberration, as determined via&#xD;
             the MATCH Master Protocol&#xD;
&#xD;
          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment&#xD;
             assignment and must have NONE of the following cardiac criteria:&#xD;
&#xD;
               -  Clinically important abnormalities in rhythm, conduction or morphology of resting&#xD;
                  ECG (e.g. complete left bundle branch block, third degree heart block)&#xD;
&#xD;
               -  Treatment-refractory hypertension defined as a blood pressure of systolic &gt; 140&#xD;
                  mmHg and/or diastolic &gt; 90 mmHg which cannot be controlled by anti-hypertensive&#xD;
                  therapy&#xD;
&#xD;
          -  Patients must have an echocardiogram (ECHO) or a nuclear study (multigated acquisition&#xD;
             scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must&#xD;
             not have a left ventricular ejection fraction (LVEF) &lt; the institutional lower limit&#xD;
             of normal (LLN). If the LLN is not defined at a site, the LVEF must be &gt; 50% for the&#xD;
             patient to be eligible&#xD;
&#xD;
          -  Patients who previously received monoclonal antibody therapy (e.g., ipilimumab,&#xD;
             nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more&#xD;
             weeks before starting on trametinib&#xD;
&#xD;
          -  Patients with glioblastoma must have histologically or radiographically confirmed&#xD;
             recurrent or progressive World Health Organization (WHO) grade 4 glioma&#xD;
             (glioblastoma).&#xD;
&#xD;
               -  NOTE: All baseline and post-baseline disease assessments must be performed using&#xD;
                  contrast-enhanced cranial magnetic resonance imaging (MRI) or contrast-enhanced&#xD;
                  computed tomography (CT) for subjects who cannot have MRI performed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a history of interstitial lung disease or pneumonitis are excluded&#xD;
&#xD;
          -  Patients must not have known hypersensitivity to trametinib or compounds of similar&#xD;
             chemical or biologic composition or to dimethyl sulfoxide (DMSO)&#xD;
&#xD;
          -  Patients must not have a history or current evidence/risk of retinal vein occlusion&#xD;
             (RVO). An eye exam is required at baseline&#xD;
&#xD;
          -  Patients who previously received prior treatment with other MEK inhibitors (including,&#xD;
             but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655&#xD;
             [CH4987655], GDC-0623 and pimasertib) will be excluded&#xD;
&#xD;
          -  Patients with uveal melanoma are excluded&#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>Jason J Luke</last_name>
    <role>Principal Investigator</role>
    <affiliation>ECOG-ACRIN Cancer Research Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ECOG-ACRIN Cancer Research Group</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <results_first_submitted>July 12, 2023</results_first_submitted>
  <results_first_submitted_qc>August 2, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">August 4, 2023</results_first_posted>
  <last_update_submitted>August 8, 2023</last_update_submitted>
  <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trametinib</mesh_term>
    <mesh_term>Dimethyl Sulfoxide</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>August 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT04439357/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Seven patients were assigned to Subprotocol S2, 6 from screening cohort and 1 from outside laboratory. Of the 7 patients, 4 patients were enrolled in arm S2 between July 2016 and January 2019.</recruitment_details>
      <pre_assignment_details>To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For the subprotocol S2, patients had to have a qualifying GNAQ or GNA11 actionable mutation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Trametinib)</title>
          <description>Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Trametinib Dimethyl Sulfoxide: Given PO</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible and Started Protocol Therapy</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Disease Progression</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Eligible and treated patients</population>
      <group_list>
        <group group_id="B1">
          <title>Treatment (Trametinib)</title>
          <description>Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Trametinib Dimethyl Sulfoxide: Given PO</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="54" upper_limit="76"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="4"/>
                  </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="0"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate (ORR)</title>
        <description>Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR.</description>
        <time_frame>Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
        <population>Patients who were eligible and received protocol treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Trametinib)</title>
            <description>Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Trametinib Dimethyl Sulfoxide: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR.</description>
          <population>Patients who were eligible and received protocol treatment</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% 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="1.3" upper_limit="75.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>6-month Progression-free Survival (PFS) Rate</title>
        <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.</description>
        <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined</time_frame>
        <population>Patients who were eligible and received protocol treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Trametinib)</title>
            <description>Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Trametinib Dimethyl Sulfoxide: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>6-month Progression-free Survival (PFS) Rate</title>
          <description>Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.</description>
          <population>Patients who were eligible and received protocol treatment</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>90% 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="50" lower_limit="22" upper_limit="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.</description>
        <time_frame>Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration</time_frame>
        <population>Patients who were eligible and received protocol treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Trametinib)</title>
            <description>Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Trametinib Dimethyl Sulfoxide: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.</description>
          <population>Patients who were eligible and received protocol treatment</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>90% 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="6.5" lower_limit="1.8" upper_limit="NA">Median PFS 90% CI upper bound could not be determined due to insufficient number of participants with events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration.</time_frame>
      <desc>All patients enrolled were included in the all-cause mortality analysis and all patients received protocol treatment were included in the toxicity analysis</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Trametinib)</title>
          <description>Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Trametinib Dimethyl Sulfoxide: Given PO</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE 4.0</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="3" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE 4.0</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="4" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Investigations - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urine discoloration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Reproductive system and breast disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Hirsutism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Statistician</name_or_title>
      <organization>ECOG-ACRIN Statistical Office</organization>
      <phone>617-632-3012</phone>
      <email>eatrials@jimmy.harvard.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/NCT04439357
org study id: NCI-2020-03436
secondary id: NCI-2020-03436
secondary id: EAY131-S2
secondary id: EAY131-S2
secondary id: U10CA180820
secondary id: U24CA196172
nct id: NCT04439357
lead sponsor: 
has dmc: Yes
This phase II MATCH treatment trial identifies the effects of trametinib in patients whose
      cancer has genetic changes called GNAQ or GNA11 mutations. Trametinib may block proteins
      called MEK1 and MEK2, which may be needed for cancer cell growth when GNAQ or GNA11 mutations
      are present. Researchers hope to learn if trametinib will shrink this type of cancer or stop
      its growth.
PRIMARY OBJECTIVE:

      I. To evaluate the proportion of patients with objective response (OR) to targeted study
      agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

      SECONDARY OBJECTIVES:

      I. To evaluate the proportion of patients alive and progression free at 6 months of treatment
      with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple
      myeloma.

      II. To evaluate time until death or disease progression. III. To identify potential
      predictive biomarkers beyond the genomic alteration by which treatment is assigned or
      resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and
      imaging-based assessment platforms.

      IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes
      from pre- through post-therapy imaging can predict objective response and progression free
      survival and to evaluate the association between pre-treatment radiomic phenotypes and
      targeted gene mutation patterns of tumor biopsy specimens.

      OUTLINE:

      Patients receive trametinib dimethyl sulfoxide (trametinib) orally (PO) once daily (QD) on
      days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable
      toxicity.

      After completion of study treatment, patients are followed up every 3 months if less than 2
      years from study entry, and then every 6 months for year 3 from study entry.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
description: Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR.
measure: 6-month Progression-free Survival (PFS) Rate
time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS rate is determined
description: Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
measure: Progression Free Survival (PFS)
time frame: Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration
description: PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.
arm group label: Treatment (trametinib)
arm group type: Experimental
description: Patients receive trametinib dimethyl sulfoxide PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Trametinib Dimethyl Sulfoxide
description: Given PO
arm group label: Treatment (trametinib)
other name: Mekinist
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jason J Luke
role: Principal Investigator
affiliation: ECOG-ACRIN Cancer Research Group
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Neoplasms
mesh term: Multiple Myeloma
mesh term: Trametinib
mesh term: Dimethyl Sulfoxide
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 