xml: <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/NCT06007924</url>
    </required_header>
    <id_info>
      <org_study_id>23-007</org_study_id>
      <nct_id>NCT06007924</nct_id>
    </id_info>
    <brief_title>A Study of Avutometinib and Defactinib in People With Thyroid Cancer</brief_title>
    <official_title>Phase II of Avutometinib (VS-6766) and Defactinib In RAF Dimer-Driven RAI-Refractory Differentiated and Anaplastic Thyroid Cancer Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Memorial Sloan Kettering Cancer Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Verastem, Inc.</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Memorial Sloan Kettering Cancer Center</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The researchers are doing this study to find out if the combination of avutometinib and&#xD;
        defactinib is an effective treatment for RAF dimer-driven radioiodine-refractory&#xD;
        differentiated thyroid cancer or anaplastic thyroid cancer. The researchers will also test&#xD;
        whether avutometinib and defactinib is a safe treatment that causes few or mild side effects.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 16, 2023</start_date>
    <completion_date type="Anticipated">August 16, 2027</completion_date>
    <primary_completion_date type="Anticipated">August 16, 2027</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>This is a phase II clinical trial evaluating avutometinib in combination with defactinib in radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC) (Cohort A) and anaplastic thyroid cancer (ATC) (Cohort B) patients.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>overall response rate (ORR) cohort A</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>overall response rate (ORR) cohort B</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Thyroid Cancer</condition>
    <arm_group>
      <arm_group_label>Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will be treated with avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily, both 3 weeks on/1 week off.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Anaplastic thyroid cancer (ATC)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients will be treated with avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily, both 3 weeks on/1 week off.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Avutometinib</intervention_name>
      <description>Avutometinib 3.2 mg twice weekly 3 weeks on/1 week off</description>
      <arm_group_label>Anaplastic thyroid cancer (ATC)</arm_group_label>
      <arm_group_label>Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Defactinib</intervention_name>
      <description>Defactinib 200 mg twice daily 3 weeks on/1 week off</description>
      <arm_group_label>Anaplastic thyroid cancer (ATC)</arm_group_label>
      <arm_group_label>Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          Cohort A will enroll RAIR, R/M DTC patients with RAF dimer-driven disease.&#xD;
  &#xD;
          Cohort B will enroll ATC patients with RAF dimer-driven disease.&#xD;
  &#xD;
            -  Cohort A only: Patients must have pathologically or cytologically confirmed&#xD;
               differentiated thyroid cancer of follicular origin (including papillary thyroid&#xD;
               carcinoma, follicular thyroid carcinoma, hurthle cell carcinomas, poorly&#xD;
               differentiated thyroid carcinoma and their respective variants).&#xD;
  &#xD;
            -  Cohort B only: Patients must have anaplastic thyroid carcinoma.&#xD;
  &#xD;
            -  Confirmation in a CLIA certified laboratory that one of the patient's thyroid tumors&#xD;
               (primary tumor, recurrent tumor, or metastases) possess one of the following genetic&#xD;
               alterations: RAS mutation, NF1 mutation, RET rearrangement, NTRK rearrangement, ALK&#xD;
               rearrangement, Class 2 or 3 BRAF alterations (non-V600E/K mutations or&#xD;
               rearrangements).&#xD;
  &#xD;
            -  Cohort A only: Evidence of progressive disease (e.g. presence of new or growing&#xD;
               lesion(s) on radiologic imaging and/or new or worsening tumor-related symptoms) within&#xD;
               14 months of study enrollment.&#xD;
  &#xD;
            -  Cohort A only: Patients must have recurrent or metastatic disease not amenable to&#xD;
               curative surgery or radiation.&#xD;
  &#xD;
            -  Patients with any number of prior therapies will be eligible.&#xD;
  &#xD;
            -  Patients must have RECIST v1.1 measurable disease.&#xD;
  &#xD;
            -  Age ≥ 18 years.&#xD;
  &#xD;
            -  ECOG performance status of 0 or 1.&#xD;
  &#xD;
            -  For Cohort A only: Patients must have not had recent treatment for thyroid cancer as&#xD;
               defined as:&#xD;
  &#xD;
                 -  No prior RAI therapy is allowed &lt;6 months prior to initiation of therapy on this&#xD;
                    protocol. A diagnostic study using &lt;10 mCi of RAI is not considered RAI therapy&#xD;
  &#xD;
                 -  No external beam radiation therapy &lt;4weeks prior to initiation of therapy on this&#xD;
                    protocol.&#xD;
  &#xD;
                 -  No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed&#xD;
                    &lt;4 weeks prior to the initiation of therapy on this protocol&#xD;
  &#xD;
            -  For Cohort A only: Patients must have RAI-refractory disease, defined as one of the&#xD;
               following:&#xD;
  &#xD;
                 -  Total lifetime dose of radioiodine &gt; 600 mCi&#xD;
  &#xD;
                 -  A tumor that is not radioiodine-avid on a diagnostic radioiodine scan performed&#xD;
  &#xD;
                 -  A radioiodine-avid metastatic lesion which progressed despite radioiodine&#xD;
                    treatment given 6 months or more prior to study entry in the study. There are no&#xD;
                    size limitations for the index lesions used to satisfy this entry criterion&#xD;
  &#xD;
                 -  The presence of at least one fluorodeoxyglucose (FDG) avid lesion.&#xD;
  &#xD;
            -  Patients must be able to swallow and retain orally-administered pills without any&#xD;
               clinically significant gastrointestinal abnormalities that may alter absorption, such&#xD;
               as malabsorption syndrome or major resection of the stomach or bowels.&#xD;
  &#xD;
            -  Adequate recovery from toxicities related to prior treatments to at least Grade 1 by&#xD;
               CTCAE v 5.0. Exceptions include alopecia and peripheral neuropathy grade ≤ 2.&#xD;
  &#xD;
            -  Patients must have tissue from the primary tumor or metastases available for&#xD;
               correlative studies. Either a paraffin block or at least 20 unstained slides are&#xD;
               acceptable (30 unstained slides would be ideal). (If less than twenty unstained slides&#xD;
               are available and a paraffin bloc is not available, the patient may be able to&#xD;
               participate at the discretion of the investigator).&#xD;
  &#xD;
            -  Patients must agree to undergo two research biopsies of (a) malignant lesion(s). Tumor&#xD;
               tissue obtained prior to study consent or treatment as part of standard of care can&#xD;
               also be submitted in lieu of performance of the first pre-treatment biopsy if the&#xD;
               Principal Investigator deems it to be of sufficient quantity/quality/timeliness.&#xD;
               Patients may also be exempt from biopsy if 1) the investigator or person performing&#xD;
               the biopsy judges that no tumor is accessible for biopsy, 2) the investigator or&#xD;
               person performing the biopsy feels that the biopsy poses too great of a risk to the&#xD;
               patient (including if conduct of the biopsy will result in an unacceptable delay in&#xD;
               therapy), or 3) the patient cannot be safely removed from anti-coagulation therapy (if&#xD;
               the anti-coagulation therapy needs to be temporarily held for the biopsy procedure).&#xD;
               If the only tumor accessible for biopsy is also the only lesion that can be used for&#xD;
               RECIST v1.1 response evaluation, then the patient may be exempt from biopsy. If the&#xD;
               investigator deems a second research biopsy to be high risk after a patient has&#xD;
               completed the first research biopsy, the patient may be exempt from the second biopsy.&#xD;
               Biopsies of lesions that are in proximity to any vital neurovascular structures that&#xD;
               can be considered high risk procedures will not be biopsied.&#xD;
  &#xD;
            -  Baseline QTc interval &lt; 460 ms for women and ≤450 ms for men using Frederica's QT&#xD;
               correction formula. NOTE: This criterion does not apply to patients with a right or&#xD;
               left bundle branch block.&#xD;
  &#xD;
            -  Adequate cardiac function wit left ventricular ejection fraction &gt;50% by&#xD;
               echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan.&#xD;
  &#xD;
            -  Screening laboratory values must meet the following criteria:&#xD;
  &#xD;
                 -  WBC ≥ 2000/μL&#xD;
  &#xD;
                 -  Neutrophils ≥ 1000/μL&#xD;
  &#xD;
                 -  Platelets ≥ 100 x10^3 /μL&#xD;
  &#xD;
                 -  Hemoglobin &gt; 9.0 g/dL&#xD;
  &#xD;
                 -  AST/ALT ≤ 2.5 x ULN (of &lt; 5x ULN in patients with liver metastases)&#xD;
  &#xD;
                 -  Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have&#xD;
                    total bilirubin &lt; 3.0 mg/dL)&#xD;
  &#xD;
                 -  International normalized ratio (INR) &lt; 1.5 and partial thromboplastin time (PTT)&#xD;
                    &lt; 1.5 x ULN in the absence of anticoagulation or therapeutic levels in the&#xD;
                    presence of anticoagulation.&#xD;
  &#xD;
                 -  Albumin ≥ 3.0 g/dL (451 μmole/L)&#xD;
  &#xD;
                 -  Creatine phosphokinase (CPK) ≤ 2.5 x ULN&#xD;
  &#xD;
                 -  Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 50 mL/min (if using&#xD;
                    the Cockcroft-Gault formula below)&#xD;
  &#xD;
                 -  Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in&#xD;
                    mg/dL&#xD;
  &#xD;
                 -  Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in&#xD;
                    mg/dL&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Symptomatic brain metastases requiring steroids or other local interventions. Patients&#xD;
               with previously diagnosed brain metastases are eligible if they have completed their&#xD;
               treatment and have recovered from the acute effects of radiation therapy or surgery&#xD;
               prior to study entry, have discontinued corticosteroid treatment for these metastases&#xD;
               for at least 2 weeks prior to first dose of study therapy, and are neurologically&#xD;
               stable, with no evidence of interim progression. Patients with new asymptomatic CNS&#xD;
               metastases detected during the screening period must receive radiation therapy and/or&#xD;
               surgery for CNS metastases. Following treatment, these patients may then be eligible&#xD;
               if all other criteria are met.&#xD;
  &#xD;
            -  Prior therapy with a MEK 1/2 inhibitor or an inhibitor that targets Class II/Class III&#xD;
               BRAF alterations or a FAK inhibitor (with the exception of patients who received these&#xD;
               therapies for a defined period of time to enhance radioiodine activity).&#xD;
  &#xD;
            -  Patient who have had systemic investigational anti-cancer therapy within 4 weeks of&#xD;
               the first dose of study therapy.&#xD;
  &#xD;
            -  Major surgery within 4 weeks (excluding placement of vascular access), minor surgery&#xD;
               within 2 weeks, or palliative radiotherapy within 1 week of the first dose of study&#xD;
               drug.&#xD;
  &#xD;
            -  Treatment with warfarin. Patients on warfarin for deep vein thrombosis/pulmonary&#xD;
               embolism should be converted to low-molecular-weight heparin (LMWH) or direct oral&#xD;
               anticoagulants (DOACs).&#xD;
  &#xD;
            -  Concomitant use of strong inhibitors and inducers of CYP3A4 (see Appendix 1 in Section&#xD;
               18). Patients should refrain from consumption of grapefruit, grapefruit juice and St.&#xD;
               John's Wort, and other medications (with or without prescriptions), supplements,&#xD;
               herbal remedies or foods that are strong inhibitors or inducers of CYP3A4 during&#xD;
               treatment&#xD;
  &#xD;
            -  Concomitant use of strong CYP2C9 inhibtors or inducers. For additional guidance see&#xD;
               https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteract&#xD;
               ions-table-substrates-inhibitors-and-inducers&#xD;
  &#xD;
            -  Concomitant use of strong P-glycoprotein(P-gp) inhibitors or inducers. For additional&#xD;
               guidance see&#xD;
               https://www.uptodate.com/contents/image/print?imageKey=EM%2F73326&amp;topicKey=HEME%2F1370&#xD;
               &amp;source=outlinelink&#xD;
  &#xD;
            -  Patients with history of glaucoma, history of retinal vein occlusion (RVO),&#xD;
               predisposing factors for RVO, including uncontrolled hypertension, uncontrolled&#xD;
               diabetes.&#xD;
  &#xD;
            -  Patients with a history of retinal pathology or evidence of visible retinal pathology&#xD;
               that is considered a risk factor for RVO, such as an intraocular pressure &gt; 21 mmHg&#xD;
  &#xD;
            -  Cohort A only: Symptomatic metastatic brain or leptomeningeal tumors (asymptomatic or&#xD;
               treated metastatic brain or leptomeningeal tumors are allowed).&#xD;
  &#xD;
            -  Treatment-refractory hypertension defined as a blood pressure of systolic &gt;140 mmHg&#xD;
               and/or diastolic &gt;90 mmHg which cannot be controlled by anti-hypertensive therapy.&#xD;
  &#xD;
            -  Patients with active hepatitis B infection (HBV surface antigen positive).&#xD;
  &#xD;
            -  Subject is known to be positive for Human Immunodeficiency Virus (HIV) or active&#xD;
               Hepatitis C Virus (HCV). Testing for HIV or Hepatitis C prior to initiation of the&#xD;
               study drug is not required. If a patient has a known history of treated HCV, then a&#xD;
               viral load is required to confirm clearance of infection.&#xD;
  &#xD;
            -  Known severe acute respiratory syndrome coronavirus 2 SARS-Cov2 infection (clinical&#xD;
               symptoms) ≤28 days prior to first dose of study therapy.&#xD;
  &#xD;
            -  History of rhabdomyolysis.&#xD;
  &#xD;
            -  Concurrent congestive heart failure, prior history of class III/ IV cardiac disease&#xD;
               (New York Heart Association [NYHA]), myocardial infarction within the last 6 months,&#xD;
               unstable arrhythmias, unstable angina or severe obstructive pulmonary disease.&#xD;
  &#xD;
            -  Subjects with the inability to swallow oral medications or impaired gastrointestinal&#xD;
               absorption due to gastrectomy or active inflammatory bowel disease&#xD;
  &#xD;
            -  Any other medical condition (e.g., cardiac, gastrointestinal, pulmonary, psychiatric,&#xD;
               neurological, genetic, etc.) that in the opinion of the Investigator would places the&#xD;
               patient at unacceptably high risk for toxicity.&#xD;
  &#xD;
            -  Patients who are pregnant or breastfeeding.&#xD;
  &#xD;
            -  Patients with hypersensitivity to mannitol, magnesium stearate, HPMC (hydroxypropyl&#xD;
               methylcellulose) shells&#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>Alan Ho, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Alan Ho, MD, PhD</last_name>
      <phone>646-608-3774</phone>
      <email>hoa@mskcc.org</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>David Pfister, MD</last_name>
      <phone>646-888-4237</phone>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)</name>
        <address>
          <city>Basking Ridge</city>
          <state>New Jersey</state>
          <zip>07920</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD. PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Monmouth (Limited Protocol Activities)</name>
        <address>
          <city>Middletown</city>
          <state>New Jersey</state>
          <zip>07748</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD, PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Bergen (Limited Protocol Activities)</name>
        <address>
          <city>Montvale</city>
          <state>New Jersey</state>
          <zip>07645</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD, PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Cancer Center Suffolk - Commack (Limited Protocol Activities)</name>
        <address>
          <city>Commack</city>
          <state>New York</state>
          <zip>11725</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD, PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Westchester (Limited Protocol Activities)</name>
        <address>
          <city>Harrison</city>
          <state>New York</state>
          <zip>10604</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD, PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Cancer Center (All Protocol Activities)</name>
        <address>
          <city>New York</city>
          <state>New York</state>
          <zip>10065</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD. PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
      <contact_backup>
        <last_name>David Pfister, MD</last_name>
        <phone>646-888-4237</phone>
      </contact_backup>
      <investigator>
        <last_name>Alan Ho, MD, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Memorial Sloan Kettering Nassau (Limited Protocol Activities)</name>
        <address>
          <city>Rockville Centre</city>
          <state>New York</state>
          <zip>11553</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Alan Ho, MD, PhD</last_name>
        <phone>646-608-3774</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <link>
      <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
      <description>Memorial Sloan Kettering Cancer Center</description>
    </link>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 17, 2023</study_first_submitted>
    <study_first_submitted_qc>August 17, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 23, 2023</study_first_posted>
    <last_update_submitted>August 17, 2023</last_update_submitted>
    <last_update_submitted_qc>August 17, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Avutometinib</keyword>
    <keyword>Defactinib</keyword>
    <keyword>23-007</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thyroid Neoplasms</mesh_term>
      <mesh_term>Thyroid Diseases</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06007924
  org study id: 23-007
  nct id: NCT06007924
  lead sponsor: 
  collaborator: 
  is fda regulated drug: Yes
  is fda regulated device: No
  The researchers are doing this study to find out if the combination of avutometinib and
        defactinib is an effective treatment for RAF dimer-driven radioiodine-refractory
        differentiated thyroid cancer or anaplastic thyroid cancer. The researchers will also test
        whether avutometinib and defactinib is a safe treatment that causes few or mild side effects.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: This is a phase II clinical trial evaluating avutometinib in combination with defactinib in radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC) (Cohort A) and anaplastic thyroid cancer (ATC) (Cohort B) patients.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: overall response rate (ORR) cohort A
  time frame: up to 2 years
  description: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
  measure: overall response rate (ORR) cohort B
  time frame: up to 2 years
  description: Response and progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1)
  arm group label: Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)
  arm group type: Experimental
  description: Patients will be treated with avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily, both 3 weeks on/1 week off.
  arm group label: Anaplastic thyroid cancer (ATC)
  arm group type: Experimental
  description: Patients will be treated with avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily, both 3 weeks on/1 week off.
  intervention type: Drug
  intervention name: Avutometinib
  description: Avutometinib 3.2 mg twice weekly 3 weeks on/1 week off
  arm group label: Anaplastic thyroid cancer (ATC)
  arm group label: Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)
  intervention type: Drug
  intervention name: Defactinib
  description: Defactinib 200 mg twice daily 3 weeks on/1 week off
  arm group label: Anaplastic thyroid cancer (ATC)
  arm group label: Radioiodine-refractory (RAIR), recurrent and/or metastatic differentiated thyroid cancer (DTC)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Alan Ho, MD, PhD
  role: Principal Investigator
  affiliation: Memorial Sloan Kettering Cancer Center
  last name: Alan Ho, MD, PhD
  phone: 646-608-3774
  email: hoa@mskcc.org
  last name: David Pfister, MD
  phone: 646-888-4237
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  contact backup: 
  investigator: 
  facility: 
  status: Recruiting
  contact: 
  country: United States
  url: http://www.mskcc.org/mskcc/html/44.cfm
  description: Memorial Sloan Kettering Cancer Center
  responsible party type: Sponsor
  mesh term: Thyroid Neoplasms
  mesh term: Thyroid Diseases
  sharing ipd: Yes
  ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.