<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/NCT04439344</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-03374</org_study_id>
    <secondary_id>NCI-2020-03374</secondary_id>
    <secondary_id>EAY131-Z1A</secondary_id>
    <secondary_id>EAY131-Z1A</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <secondary_id>U24CA196172</secondary_id>
    <nct_id>NCT04439344</nct_id>
  </id_info>
  <brief_title>Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)</brief_title>
  <official_title>MATCH Treatment Subprotocol Z1A: Binimetinib in Patients With Tumors (Other Than Melanoma) With NRAS 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 investigates the good and bad effects of binimetinib in&#xD;
      patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins&#xD;
      called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is&#xD;
      present. Researchers hope to learn if binimetinib will shrink this type of cancer or stop its&#xD;
      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 binimetinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every&#xD;
      28 days in the absence of disease progression or unacceptable 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">May 31, 2016</start_date>
  <primary_completion_date type="Actual">May 3, 2019</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>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>6-Month Progression-free Survival (PFS) Rate</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, from which 6-month PFS 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. 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>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. Median PFS was estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">53</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 (binimetinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive binimetinib PO BID 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>Binimetinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (binimetinib)</arm_group_label>
    <other_name>ARRY-162</other_name>
    <other_name>ARRY-438162</other_name>
    <other_name>MEK162</other_name>
    <other_name>Mektovi</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 NRAS mutation in codon 12, 13, 61 as determined via the MATCH&#xD;
             Master Protocol&#xD;
&#xD;
          -  Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment&#xD;
             assignment and must have no clinically significant abnormalities in rhythm, conduction&#xD;
             or morphology of resting ECG (e.g. complete left bundle branch block, third degree&#xD;
             heart block)&#xD;
&#xD;
          -  Creatinine =&lt; 1.5 mg/dL, or calculated creatinine clearance (determined as per&#xD;
             Cockcroft-Gault) &gt;= 50mL/min&#xD;
&#xD;
          -  Patients must have adequate cardiac function:&#xD;
&#xD;
               -  Left ventricular ejection fraction (LVEF) &gt;= 50% as determined by a multigated&#xD;
                  acquisition (MUGA) scan or echocardiogram,&#xD;
&#xD;
               -  QTc interval =&lt; 480 ms&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must not have known hypersensitivity to binimetinib or compounds of similar&#xD;
             chemical or biologic composition&#xD;
&#xD;
          -  Patients with melanoma are excluded&#xD;
&#xD;
          -  Patients must not have any active central nervous system (CNS) lesion (i.e., those&#xD;
             with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases&#xD;
&#xD;
               -  NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if&#xD;
                  the patient remained without evidence of CNS disease progression &gt;= 3 months.&#xD;
                  Patients must be off corticosteroid therapy for &gt;= 3 weeks&#xD;
&#xD;
          -  Patients must not have a history or current evidence of retinal vein occlusion (RVO)&#xD;
             or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension,&#xD;
             history of hyperviscosity or hypercoagulability syndromes)&#xD;
&#xD;
          -  Patients must not have a history of retinal degenerative disease&#xD;
&#xD;
          -  Patients must not have a history of Gilbert's syndrome&#xD;
&#xD;
          -  Patients must not have uncontrolled arterial hypertension despite medical treatment&#xD;
&#xD;
          -  Patients must not have active hepatitis B, and/or active hepatitis C infection&#xD;
&#xD;
          -  Patients must not have neuromuscular disorders that are associated with elevated&#xD;
             creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic&#xD;
             lateral sclerosis, spinal muscular atrophy)&#xD;
&#xD;
          -  Patients must not have impairment of gastrointestinal function or gastrointestinal&#xD;
             disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea,&#xD;
             malabsorption syndrome, small bowel resection)&#xD;
&#xD;
          -  Patients who have received prior MEK inhibitors 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>James M Cleary</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>March 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>April 29, 2021</results_first_submitted>
  <results_first_submitted_qc>July 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">August 17, 2021</results_first_posted>
  <last_update_submitted>June 6, 2023</last_update_submitted>
  <last_update_submitted_qc>June 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 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>
  <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>May 16, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT04439344/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subprotocol Z1A was activated on May 31, 2016. A total of 114 patients were assigned to this arm after screening, all from screening cohort. Of the 114 patients, 53 patients were enrolled to arm Z1A in the period from May 31, 2016 and June 7, 2018.</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 Z1A, patients had to have a tumor harboring a codon 12, 13, or 61 NRAS-mutation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment (Binimetinib)</title>
          <description>Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Binimetinib: 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="53"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Started Protocol Therapy</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Eligible</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
              </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="53"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Never started threapy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ineligible</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Alternative therapy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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 (Binimetinib)</title>
          <description>Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Binimetinib: Given PO</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="47"/>
          </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="60" lower_limit="30" upper_limit="84"/>
                  </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="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="2"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                  </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="2"/>
                  </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>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be 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 (Binimetinib)</title>
            <description>Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Binimetinib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR)</title>
          <description>ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be 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="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.021" lower_limit="0.001" upper_limit="0.097"/>
                  </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. 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>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, from which 6-month PFS is determined</time_frame>
        <population>Patients who were eligible and received protocol treatment</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment (Binimetinib)</title>
            <description>Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Binimetinib: 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. 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="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.292" lower_limit="0.194" upper_limit="0.440"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</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. Median PFS was estimated using the Kaplan-Meier method.</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 (Binimetinib)</title>
            <description>Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Binimetinib: Given PO</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</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. Median PFS was estimated using the Kaplan-Meier method.</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="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" lower_limit="1.8" upper_limit="5.8"/>
                  </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 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment (Binimetinib)</title>
          <description>Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.&#xD;
Binimetinib: 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="43" subjects_at_risk="53"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </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="50"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Multi-organ failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypophosphatemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle weakness lower limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Muscle weakness upper limb</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </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="44" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Eye disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Mucositis oral</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Edema limbs</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>CPK increased</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>White blood cell decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypoalbuminemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypocalcemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Hypomagnesemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="50"/>
              </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="4" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Rash acneiform</sub_title>
                <counts group_id="E1" subjects_affected="27" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="50"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="50"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="50"/>
              </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/NCT04439344
org study id: NCI-2020-03374
secondary id: NCI-2020-03374
secondary id: EAY131-Z1A
secondary id: EAY131-Z1A
secondary id: U10CA180820
secondary id: U24CA196172
nct id: NCT04439344
lead sponsor: 
has dmc: Yes
This phase II MATCH treatment trial investigates the good and bad effects of binimetinib in
      patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins
      called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is
      present. Researchers hope to learn if binimetinib 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 binimetinib orally (PO) twice daily (BID) 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: ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
measure: 6-Month Progression-free Survival (PFS) Rate
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, from which 6-month PFS 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. 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: 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. Median PFS was estimated using the Kaplan-Meier method.
arm group label: Treatment (binimetinib)
arm group type: Experimental
description: Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Binimetinib
description: Given PO
arm group label: Treatment (binimetinib)
other name: ARRY-162
other name: ARRY-438162
other name: MEK162
other name: Mektovi
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: James M Cleary
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
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 