<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/NCT03825289</url>
  </required_header>
  <id_info>
    <org_study_id>HCI116898</org_study_id>
    <nct_id>NCT03825289</nct_id>
  </id_info>
  <brief_title>Trametinib and Hydroxychloroquine in Treating Patients With Pancreatic Cancer</brief_title>
  <acronym>THREAD</acronym>
  <official_title>THREAD: A Phase I Trial of Trametinib and Hydroxychloroquine in Patients With Advanced Pancreatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase I trial studies the sides effects and best dose of hydroxychloroquine when given&#xD;
      together with trametinib in treating patients with pancreatic cancer that has spread to&#xD;
      nearby tissue, lymph nodes or other places in the body and cannot be removed by surgery.&#xD;
      Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell&#xD;
      growth. Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to&#xD;
      stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,&#xD;
      or by stopping them from spreading. Giving trametinib together with hydroxychloroquine may&#xD;
      work better in treating patients with pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the recommended phase II dose of hydroxychloroquine in combination with&#xD;
      trametinib as assessed by the occurrence of dose-limiting toxicities (DLTs).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 18, 2019</start_date>
  <completion_date type="Anticipated">January 18, 2025</completion_date>
  <primary_completion_date type="Anticipated">January 18, 2024</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of dose-limiting toxicities during the DLT assessment window.</measure>
    <time_frame>At 28 days</time_frame>
    <description>To determine the recommended phase II dose (RP2D) hydroxychloroquine in combination with trametinib.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (AEs) for the duration of study treatment</measure>
    <time_frame>30 days after last dose</time_frame>
    <description>To assess the safety of the combination of trametinib and hydroxychloroquine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response Rate</measure>
    <time_frame>5 years</time_frame>
    <description>To assess the efficacy of the combination of trametinib and hydroxychloroquine</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">39</enrollment>
  <condition>Metastatic Pancreatic Carcinoma</condition>
  <condition>Stage II Pancreatic Cancer</condition>
  <condition>Stage IIA Pancreatic Cancer</condition>
  <condition>Stage IIB Pancreatic Cancer</condition>
  <condition>Stage III Pancreatic Cancer</condition>
  <condition>Stage IV Pancreatic Cancer</condition>
  <condition>Unresectable Pancreatic Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (trametinib, hydroxychloroquine)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive trametinib PO QD on days 1-28 and hydroxychloroquine PO QD or 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>Hydroxychloroquine</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (trametinib, hydroxychloroquine)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trametinib</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Treatment (trametinib, hydroxychloroquine)</arm_group_label>
    <other_name>GSK1120212</other_name>
    <other_name>JTP-74057</other_name>
    <other_name>MEK Inhibitor GSK1120212</other_name>
    <other_name>Mekinist</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject with histologically confirmed metastatic or locally advanced, unresectable&#xD;
             pancreatic carcinoma&#xD;
&#xD;
          -  Subject is willing to provide a baseline biopsy.&#xD;
&#xD;
          -  EXPANSION COHORT ONLY: Subject must have progressed during or after two standard of&#xD;
             care lines of treatment or refused standard of care options.&#xD;
&#xD;
          -  Subject must have computed tomography (CT) measurable disease by Response Evaluation&#xD;
             Criteria in Solid Tumors (RECIST) 1.1 criteria&#xD;
&#xD;
          -  Subject must be able and willing to undergo disease assessment while on study and&#xD;
             afterwards, if removed for reason other than progression&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status =&lt; 2&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;= 1.5 x 10^9/L&#xD;
&#xD;
          -  Platelet count &gt;= 100 x 10^9/L&#xD;
&#xD;
          -  Hemoglobin &gt;= 9 g/dL&#xD;
&#xD;
          -  Total bilirubin level =&lt; 1.5 x the upper limit of normal (ULN) range&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels =&lt; 3 x ULN.&#xD;
             Patients with liver metastases will be allowed to enroll with AST and ALT levels =&lt; 5&#xD;
             x ULN&#xD;
&#xD;
          -  Estimated creatinine clearance &gt;= 30 mL/min according to the Cockcroft-Gault formula&#xD;
             (or local institutional standard method)&#xD;
&#xD;
          -  Negative serum or urine pregnancy test at screening for women of childbearing&#xD;
             potential&#xD;
&#xD;
          -  Highly effective contraception for both male and female subjects throughout the study&#xD;
             and for at least 4 months after last study treatment administration&#xD;
&#xD;
          -  Recovery to baseline or =&lt; grade 1 Common Terminology Criteria for Adverse Events&#xD;
             (CTCAE) version (v)5.0 from toxicities related to any prior treatments, unless adverse&#xD;
             event (AE)(s) are clinically nonsignificant and/or stable on supportive therapy&#xD;
&#xD;
          -  Able to provide informed consent and willing to sign an approved consent form that&#xD;
             conforms to federal and institutional guidelines&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject who have received systemic antineoplastic therapy (including unconjugated&#xD;
             therapeutic antibodies and toxin immunoconjugates) or any investigational therapy&#xD;
             within 2 weeks or within 5 half-lives of the investigational therapy prior to starting&#xD;
             study treatment, whichever is shorter.&#xD;
&#xD;
          -  Subject who have received radiotherapy within 2 weeks prior to the first dose of study&#xD;
             treatment. Localized radiation therapy for the treatment of symptomatic bone&#xD;
             metastasis is allowed during that timeframe&#xD;
&#xD;
          -  Subjects who have undergone major surgery =&lt; 3 weeks prior to starting study drug or&#xD;
             who have not recovered from side effects of such procedure&#xD;
&#xD;
          -  Patients with multiple primary malignancies may be enrolled if non-pancreatic ductal&#xD;
             adenocarcinoma (PDAC) tumor(s) does not have the potential to interfere with the&#xD;
             safety or efficacy assessment of the investigational regimen as determined by treating&#xD;
             investigator and do not require active treatment&#xD;
&#xD;
          -  Known brain metastases or cranial epidural disease unless adequately treated with&#xD;
             radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks&#xD;
             before first dose of study treatment. Eligible subjects must be neurologically&#xD;
             asymptomatic and without corticosteroid treatment at the time of first dose of study&#xD;
             treatment&#xD;
&#xD;
          -  History or current evidence of retinal vein occlusion (RVO) or current risk factors&#xD;
             for RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity&#xD;
             or hypercoagulability syndromes)&#xD;
&#xD;
          -  History of active major bleeding.&#xD;
&#xD;
          -  Patients whom thromboembolic prophylaxis is medically contraindicated per the treating&#xD;
             investigator's assessment.&#xD;
&#xD;
          -  Current evidence of uncontrolled, significant intercurrent illness including, but not&#xD;
             limited to, the following conditions:&#xD;
&#xD;
               -  Cardiovascular disorders:&#xD;
&#xD;
                    -  Congestive heart failure New York Heart Association class 3 or 4, unstable&#xD;
                       angina pectoris, serious cardiac arrhythmias.&#xD;
&#xD;
                    -  Stroke (including transient ischemic attack [TIA]), myocardial infarction&#xD;
                       (MI), or other ischemic event, or thromboembolic event (eg, deep venous&#xD;
                       thrombosis, pulmonary embolism) within 3 months before first dose. The&#xD;
                       presence of an asymptomatic portal vein thrombosis will not preclude study&#xD;
                       participation.&#xD;
&#xD;
               -  History of glucose-6-phosphate dehydrogenase (G6PD) deficiency&#xD;
&#xD;
               -  History of seizures&#xD;
&#xD;
               -  Patients who are planning on embarking on a new strenuous exercise regimen after&#xD;
                  first dose of study treatment. Muscular activities, such as strenuous exercise,&#xD;
                  that can result in significant increases in plasma creatine kinase (CK) levels&#xD;
                  should be avoided while on study treatment&#xD;
&#xD;
               -  Patients who have neuromuscular disorders that are associated with elevated CK&#xD;
                  (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral&#xD;
                  sclerosis, spinal muscular atrophy)&#xD;
&#xD;
               -  Impairment of gastrointestinal function or gastrointestinal disease (e.g.,&#xD;
                  ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption&#xD;
                  syndrome, or small bowel resection that under the judgment of the principal&#xD;
                  investigator [PI] may impair absorption of study drugs)&#xD;
&#xD;
               -  Any other condition that would, in the Investigator?s judgment, contraindicate&#xD;
                  the patient?s participation in the clinical study due to safety concerns or&#xD;
                  compliance with clinical study procedures, e.g., infection/inflammation,&#xD;
                  intestinal obstruction, unable to swallow medication.(patients may not receive&#xD;
                  drug through a feeding tube), social/ psychological issues, etc&#xD;
&#xD;
          -  Screening corrected QT interval by Fridericia (QTcF) &gt; 500 msec&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV), unless patient is on effective&#xD;
             anti-retroviral therapy with undetectable viral load within 6 months are eligible for&#xD;
             this trial&#xD;
&#xD;
          -  Known chronic hepatitis B virus, unless hepatitis B virus (HBV) viral load is&#xD;
             undetectable&#xD;
&#xD;
          -  Known history of hepatitis C virus (HCV) infection, unless treated and cured; for&#xD;
             patients with HCV infection who are currently on treatment, they are eligible if they&#xD;
             have an undetectable HCV viral load&#xD;
&#xD;
          -  Medical, psychiatric, cognitive or other conditions that may compromise the patient's&#xD;
             ability to understand the patient information, give informed consent, comply with the&#xD;
             study protocol or complete the study&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a&#xD;
             female after conception and until the termination of gestation, confirmed by a&#xD;
             positive human chorionic gonadotropin (hCG) laboratory test&#xD;
&#xD;
          -  Sexually active males who are not willing to use a condom during intercourse while&#xD;
             taking the drug and for 4 months after stopping treatment. A condom is also required&#xD;
             to be used by vasectomized men in order to prevent delivery of the drug via seminal&#xD;
             fluid&#xD;
&#xD;
          -  Known prior severe hypersensitivity to investigational product or any component in its&#xD;
             formulations, including known severe hypersensitivity reactions to monoclonal&#xD;
             antibodies (National Cancer institute [NCI] CTCAE v5.0 grade &gt;= 3)&#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>Conan Kinsey, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Huntsman Cancer Institute/ University of Utah</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Susan Sharry</last_name>
    <phone>801-585-3453</phone>
    <email>susan.sharry@hci.utah.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Conan G. Kinsey</last_name>
      <phone>801-585-0255</phone>
      <email>Conan.Kinsey@hci.utah.edu</email>
    </contact>
    <investigator>
      <last_name>Conan G. Kinsey</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 30, 2019</study_first_submitted>
  <study_first_submitted_qc>January 30, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 31, 2019</study_first_posted>
  <last_update_submitted>June 30, 2023</last_update_submitted>
  <last_update_submitted_qc>June 30, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 5, 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>Carcinoma</mesh_term>
    <mesh_term>Pancreatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydroxychloroquine</mesh_term>
    <mesh_term>Trametinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03825289
org study id: HCI116898
nct id: NCT03825289
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This phase I trial studies the sides effects and best dose of hydroxychloroquine when given
      together with trametinib in treating patients with pancreatic cancer that has spread to
      nearby tissue, lymph nodes or other places in the body and cannot be removed by surgery.
      Trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell
      growth. Drugs used in chemotherapy, such as hydroxychloroquine, work in different ways to
      stop the growth of tumor cells, either by killing the cells, by stopping them from dividing,
      or by stopping them from spreading. Giving trametinib together with hydroxychloroquine may
      work better in treating patients with pancreatic cancer.
PRIMARY OBJECTIVES:

      I. To determine the recommended phase II dose of hydroxychloroquine in combination with
      trametinib as assessed by the occurrence of dose-limiting toxicities (DLTs).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of dose-limiting toxicities during the DLT assessment window.
time frame: At 28 days
description: To determine the recommended phase II dose (RP2D) hydroxychloroquine in combination with trametinib.
measure: Incidence of adverse events (AEs) for the duration of study treatment
time frame: 30 days after last dose
description: To assess the safety of the combination of trametinib and hydroxychloroquine
measure: Response Rate
time frame: 5 years
description: To assess the efficacy of the combination of trametinib and hydroxychloroquine
arm group label: Treatment (trametinib, hydroxychloroquine)
arm group type: Experimental
description: Patients receive trametinib PO QD on days 1-28 and hydroxychloroquine PO QD or BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
intervention type: Drug
intervention name: Hydroxychloroquine
description: Given PO
arm group label: Treatment (trametinib, hydroxychloroquine)
intervention type: Drug
intervention name: Trametinib
description: Given PO
arm group label: Treatment (trametinib, hydroxychloroquine)
other name: GSK1120212
other name: JTP-74057
other name: MEK Inhibitor GSK1120212
other name: Mekinist
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Conan Kinsey, MD
role: Principal Investigator
affiliation: Huntsman Cancer Institute/ University of Utah
last name: Susan Sharry
phone: 801-585-3453
email: susan.sharry@hci.utah.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Pancreatic Neoplasms
mesh term: Hydroxychloroquine
mesh term: Trametinib
sharing ipd: No