<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/NCT04439292</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2020-03273</org_study_id>
    <secondary_id>NCI-2020-03273</secondary_id>
    <secondary_id>EAY131-H</secondary_id>
    <secondary_id>EAY131-H</secondary_id>
    <secondary_id>U10CA180820</secondary_id>
    <secondary_id>U24CA196172</secondary_id>
    <nct_id>NCT04439292</nct_id>
  </id_info>
  <brief_title>Testing Trametinib and Dabrafenib as a Potential Targeted Treatment in Cancers With BRAF Genetic Changes (MATCH-Subprotocol H)</brief_title>
  <official_title>MATCH Treatment Subprotocol H: Phase II Study of Dabrafenib and Trametinib in Patients With Tumors With BRAF V600E or V600K Mutations (Excluding Melanoma, Thyroid Cancer, Colorectal Adenocarcinoma, and Non-Small Cell Lung Cancer)</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 and dabrafenib in&#xD;
      patients whose cancer has genetic changes called BRAF V600 mutations. Dabrafenib may stop the&#xD;
      growth of cancer by blocking BRAF proteins which may be needed for cell growth. Trametinib&#xD;
      may stop the growth of cancer cells by blocking MEK proteins which, in addition to BRAF&#xD;
      proteins, may also be needed for cell growth. Researchers hope to learn if giving trametinib&#xD;
      with dabrafenib will shrink this type of cancer or stop 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 dabrafenib mesylate orally (PO) twice daily (BID) and trametinib dimethyl&#xD;
      sulfoxide PO once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of&#xD;
      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">August 12, 2015</start_date>
  <primary_completion_date type="Anticipated">October 2, 2023</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, 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>Overall survival (OS)</measure>
    <time_frame>Assessed every 3 months for =&lt; 2 years and every 6 months for year 3</time_frame>
    <description>OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.</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 is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">35</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 (dabrafenib, trametinib)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive dabrafenib mesylate PO BID and 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>Dabrafenib Mesylate</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (dabrafenib, trametinib)</arm_group_label>
    <other_name>Dabrafenib Methanesulfonate</other_name>
    <other_name>GSK2118436 Methane Sulfonate Salt</other_name>
    <other_name>GSK2118436B</other_name>
    <other_name>Tafinlar</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib Dimethyl Sulfoxide</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (dabrafenib, trametinib)</arm_group_label>
    <other_name>Mekinist</other_name>
    <other_name>Meqsel</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 a BRAF V600E or, V600K, V600R or V600D mutation, or another&#xD;
             aberration, as identified via the MATCH Master Protocol&#xD;
&#xD;
          -  Prothrombin time (PT)/International normalized ratio (INR) and partial thromboplastin&#xD;
             time (PTT) =&lt; 1.3 x institutional ULN; subjects receiving anticoagulation treatment&#xD;
             may be allowed to participate with INR established within the therapeutic range prior&#xD;
             to registration to treatment&#xD;
&#xD;
          -  Patients must have an ECHO or a nuclear study (multigated aquisition scan [MUGA] or&#xD;
             First Pass) within 4 weeks prior to registration to treatment and must not have a left&#xD;
             ventricular ejection fraction (LVEF) &lt; the institutional lower limit of normal (LLN).&#xD;
             If the LLN is not defined at a site, the LVEF must be &gt; 50% for the patient to be&#xD;
             eligible&#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 who previously received monoclonal antibody therapy (eg. ipilimumab and&#xD;
             others) must have stopped the prior therapy for 8 or more weeks before starting on&#xD;
             trametinib and dabrafenib&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a diagnosis of metastatic melanoma from a cutaneous, acral, mucosal, or&#xD;
             unknown primary site are excluded&#xD;
&#xD;
          -  Patients with a diagnosis of papillary thyroid cancer are excluded&#xD;
&#xD;
          -  Patients with a diagnosis of colorectal adenocarcinoma are excluded&#xD;
&#xD;
          -  Patients with a diagnosis of non-small cell lung cancer are excluded&#xD;
&#xD;
          -  Patients with a history of interstitial lung disease or pneumonitis are excluded&#xD;
&#xD;
          -  Patients must not have known hypersensitivity to dabrafenib and trametinib or&#xD;
             compounds of similar 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 MEK inhibitors (including, but not limited to,&#xD;
             trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and&#xD;
             pimasertib) will be excluded&#xD;
&#xD;
          -  Patients who previously received BRAF inhibitors (including, but not limited to,&#xD;
             dabrafenib (Tafinlar), vemurafenib (PLX-4720) (Zelboraf), RAF265, LGX818&#xD;
             (encorafenib), RO5212054 (PLX3603), ARQ 736, XL281 (BMS-908662), CEP-32496, and the&#xD;
             BRAF/MEK dual inhibitor (RO5126766) will be excluded&#xD;
&#xD;
          -  Patients with prior exposure to dabrafenib or trametinib on another treatment&#xD;
             subprotocol of the MATCH trial are excluded&#xD;
&#xD;
          -  Current use of a prohibited medication. Patients receiving any medications or&#xD;
             substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible.&#xD;
             Current use of, or intended ongoing treatment with: herbal remedies (e.g., St. John's&#xD;
             wort), or strong inhibitors or inducers of P-glycoprotein (Pgp) or breast cancer&#xD;
             resistance protein 1 (Bcrp1) should also be excluded&#xD;
&#xD;
          -  Patients with a history of hepatitis B virus (HBV) or hepatitis C virus (HCV)&#xD;
             infection are excluded. An exception will be patients with cleared HBV and HCV&#xD;
             infection which will be allowed on study&#xD;
&#xD;
          -  Patients with history of RAS mutation-positive tumors are not eligible regardless of&#xD;
             interval from the current study&#xD;
&#xD;
               -  NOTE: Prospective RAS testing is not required. However, if the results of&#xD;
                  previous RAS testing are known, they must be used in assessing eligibility&#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>Erin R Macrae</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>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 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>Dabrafenib</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>July 10, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT04439292/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04439292
org study id: NCI-2020-03273
secondary id: NCI-2020-03273
secondary id: EAY131-H
secondary id: EAY131-H
secondary id: U10CA180820
secondary id: U24CA196172
nct id: NCT04439292
lead sponsor: 
has dmc: Yes
This phase II MATCH treatment trial identifies the effects of trametinib and dabrafenib in
      patients whose cancer has genetic changes called BRAF V600 mutations. Dabrafenib may stop the
      growth of cancer by blocking BRAF proteins which may be needed for cell growth. Trametinib
      may stop the growth of cancer cells by blocking MEK proteins which, in addition to BRAF
      proteins, may also be needed for cell growth. Researchers hope to learn if giving trametinib
      with dabrafenib 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 dabrafenib mesylate orally (PO) twice daily (BID) and trametinib dimethyl
      sulfoxide 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: 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, 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: Overall survival (OS)
time frame: Assessed every 3 months for =< 2 years and every 6 months for year 3
description: OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.
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 is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.
arm group label: Treatment (dabrafenib, trametinib)
arm group type: Experimental
description: Patients receive dabrafenib mesylate PO BID and 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: Dabrafenib Mesylate
description: Given PO
arm group label: Treatment (dabrafenib, trametinib)
other name: Dabrafenib Methanesulfonate
other name: GSK2118436 Methane Sulfonate Salt
other name: GSK2118436B
other name: Tafinlar
intervention type: Drug
intervention name: Trametinib Dimethyl Sulfoxide
description: Given PO
arm group label: Treatment (dabrafenib, trametinib)
other name: Mekinist
other name: Meqsel
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Erin R Macrae
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: Dabrafenib
mesh term: Dimethyl Sulfoxide
provided document: 