<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/NCT02223819</url>
  </required_header>
  <id_info>
    <org_study_id>AAAO8010</org_study_id>
    <nct_id>NCT02223819</nct_id>
  </id_info>
  <brief_title>Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy</brief_title>
  <official_title>Phase II Trial of Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Columbia University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Columbia University</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>
      The study is designed to determine the 32 month rate of distant relapse in patients with&#xD;
      uveal melanoma who are at high risk of recurrence following definitive therapy with surgery&#xD;
      or radiation who receive adjuvant crizotinib; and secondarily, the overall survival and&#xD;
      disease specific survival in this patient population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Uveal melanoma is the most common primary intraocular malignancy in adults, and arises from&#xD;
      melanocytes within the choroid plexus of the eye. Melanomas of the ocular and adnexal&#xD;
      structures comprise approximately 5% of all melanomas and are biologically and prognostically&#xD;
      distinct from cutaneous melanoma. In the United States, an estimated 2000 patients are&#xD;
      diagnosed with this disease each year.&#xD;
&#xD;
      The development of metastasis in this disease is common and occurs in approximately 50% of&#xD;
      patients with posterior uveal melanoma within 15 years after the initial diagnosis and&#xD;
      treatment. Uveal melanoma is thought to be particularly resistant to systemic treatment, and&#xD;
      no systemic therapy has yet been demonstrated to improve survival. Drugs commonly used to&#xD;
      treat advanced cutaneous melanoma rarely achieve durable responses in patients with uveal&#xD;
      melanoma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 2015</start_date>
  <completion_date type="Anticipated">August 2022</completion_date>
  <primary_completion_date type="Anticipated">August 2022</primary_completion_date>
  <phase>Phase 2</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>Relapse Free Survival (RFS) rate</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>RFS rate will be defined as the percentage of patients who do not experience any new tumor growth at any site on the body distant from the primary site or death from any cause from the time of study entry to the end of the relevant timepoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) rate</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>OS will be defined as the time from treatment start to date of death or last followup and estimated using Kaplan-Meier methodology.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease-Specific Survival (DSS) time</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>DSS is defined as the time from treatment start to death due to disease or last followup.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence of treatment discontinuation due to toxicity</measure>
    <time_frame>48 weeks</time_frame>
    <description>Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Uveal Melanoma</condition>
  <arm_group>
    <arm_group_label>Crizotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will receive 48 weeks (12 four-week cycles) of crizotinib 250 mg PO twice a day (BID). Subjects will be evaluated by routine bloodwork and physical exam every 4 weeks while they are receiving crizotinib and during follow up period.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Crizotinib</intervention_name>
    <description>An anti-cancer drug acting as an anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibitor, used to treat non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in a gene called ALK.&#xD;
Crizotinib will be provided as capsules containing 200 or 250 mg of study medication for oral administration.</description>
    <arm_group_label>Crizotinib</arm_group_label>
    <other_name>Xalkori</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Primary diagnosis of uveal melanoma at least 12 mm in largest basal diameter as&#xD;
             clinically determined by the treating investigator. Cytologic determination of&#xD;
             diagnosis is not required. Size is based on clinical assessment (e.g. by ultrasound or&#xD;
             direct ophthalmoscopy) prior to enucleation or radiation therapy.&#xD;
&#xD;
          -  Definitive therapy of the primary uveal melanoma must have been performed within 90&#xD;
             days of initiating protocol therapy.&#xD;
&#xD;
          -  High-risk (class 2) uveal melanoma as determined by gene expression profiling&#xD;
&#xD;
          -  No evidence of metastatic disease.&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 70%.&#xD;
&#xD;
          -  Life expectancy of greater than 3 months.&#xD;
&#xD;
          -  Able to swallow and retain orally-administered medication and does not have 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;
          -  Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &gt;1,000 cells/mm³&#xD;
&#xD;
          -  Platelet count &gt;75,000/mm³&#xD;
&#xD;
          -  Hemoglobin &gt;9.0g/dL&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) &lt;3x upper&#xD;
             limited of normal (ULN)&#xD;
&#xD;
          -  Total bilirubin &lt;2x ULN&#xD;
&#xD;
          -  Alkaline phosphatase &lt;3x ULN&#xD;
&#xD;
          -  Serum creatinine &lt;2x ULN or a creatinine clearance &gt; 60mL/min&#xD;
&#xD;
          -  Note: Patients with hyperbilirubinemia clinically consistent with an inherited&#xD;
             disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the&#xD;
             discretion of the treating physician and/or the principal investigator.&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for&#xD;
             the duration of study participation until 4 months after completion of crizotinib&#xD;
             administration. Women of child-bearing potential must have a negative serum pregnancy&#xD;
             test within 14 days prior to study entry. Should a woman become pregnant or suspect&#xD;
             she is pregnant while she or her partner is participating in this study, she should&#xD;
             inform her treating physician immediately. Men treated or enrolled on this protocol&#xD;
             must also agree to use adequate contraception prior to the study, for the duration of&#xD;
             study therapy, and 4 months after completion of crizotinib administration.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of another malignancy except for those who have been disease-free for 3 years,&#xD;
             or patients with a history of completely resected non-melanoma skin cancer and/or&#xD;
             patients with indolent secondary malignancies not requiring active therapy, are&#xD;
             eligible. Consult the study Principal Investigator if unsure whether second&#xD;
             malignancies meet the requirements specified above.&#xD;
&#xD;
          -  Any major surgery or extensive radiotherapy (except that which is required for&#xD;
             definitive treatment of primary uveal melanoma), chemotherapy with delayed toxicity,&#xD;
             biologic therapy, or immunotherapy within 21 days prior to initiation of study&#xD;
             therapy.&#xD;
&#xD;
          -  History of prior crizotinib use.&#xD;
&#xD;
          -  Use of other investigational drugs within 28 days (or five half-lives, whichever is&#xD;
             shorter; with a minimum of 14 days from the last dose) preceding the first dose of&#xD;
             study therapy and during the study.&#xD;
&#xD;
          -  Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs&#xD;
             chemically related to crizotinib.&#xD;
&#xD;
          -  Concurrent administration of crizotinib and a strong inhibitor or inducer of CYP3A is&#xD;
             not permitted. Many over-the-counter and dietary supplements also inhibit or induce&#xD;
             CYP3A and thus are prohibited.&#xD;
&#xD;
          -  A QT interval corrected for heart rate using the Bazett's formula QTcB ≥ 480 msec.&#xD;
&#xD;
          -  Concurrent administration of crizotinib and agents that can cause QTc prolongation is&#xD;
             not permitted.&#xD;
&#xD;
          -  Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C&#xD;
             Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection,&#xD;
             which will be allowed). HIV-positive patients on combination antiretroviral therapy&#xD;
             are ineligible because of the potential for pharmacokinetic interactions with&#xD;
             crizotinib. In addition, these patients are at increased risk of lethal infections&#xD;
             when treated with marrow-suppressive therapy.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements.&#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>Richard Carvajal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor of Medicine at the Columbia University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mount Sinai Comprehensive Cancer Center</name>
      <address>
        <city>Miami Beach</city>
        <state>Florida</state>
        <zip>33140</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia Univeristy Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>August 20, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>June 28, 2022</last_update_submitted>
  <last_update_submitted_qc>June 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Columbia University</investigator_affiliation>
    <investigator_full_name>Richard D. Carvajal</investigator_full_name>
    <investigator_title>Associate Professor of Medicine at the Columbia University Medical Center</investigator_title>
  </responsible_party>
  <keyword>Crizotinib</keyword>
  <keyword>14-063</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Uveal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Crizotinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 31, 2023</submitted>
    <returned>August 24, 2023</returned>
    <submitted>August 29, 2023</submitted>
    <returned>September 12, 2023</returned>
  </pending_results>
  <!-- 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/NCT02223819
org study id: AAAO8010
nct id: NCT02223819
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The study is designed to determine the 32 month rate of distant relapse in patients with
      uveal melanoma who are at high risk of recurrence following definitive therapy with surgery
      or radiation who receive adjuvant crizotinib; and secondarily, the overall survival and
      disease specific survival in this patient population.
Uveal melanoma is the most common primary intraocular malignancy in adults, and arises from
      melanocytes within the choroid plexus of the eye. Melanomas of the ocular and adnexal
      structures comprise approximately 5% of all melanomas and are biologically and prognostically
      distinct from cutaneous melanoma. In the United States, an estimated 2000 patients are
      diagnosed with this disease each year.

      The development of metastasis in this disease is common and occurs in approximately 50% of
      patients with posterior uveal melanoma within 15 years after the initial diagnosis and
      treatment. Uveal melanoma is thought to be particularly resistant to systemic treatment, and
      no systemic therapy has yet been demonstrated to improve survival. Drugs commonly used to
      treat advanced cutaneous melanoma rarely achieve durable responses in patients with uveal
      melanoma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Relapse Free Survival (RFS) rate
time frame: Up to 36 months
description: RFS rate will be defined as the percentage of patients who do not experience any new tumor growth at any site on the body distant from the primary site or death from any cause from the time of study entry to the end of the relevant timepoint.
measure: Overall Survival (OS) rate
time frame: Up to 36 months
description: OS will be defined as the time from treatment start to date of death or last followup and estimated using Kaplan-Meier methodology.
measure: Disease-Specific Survival (DSS) time
time frame: Up to 36 months
description: DSS is defined as the time from treatment start to death due to disease or last followup.
measure: Prevalence of treatment discontinuation due to toxicity
time frame: 48 weeks
description: Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.
arm group label: Crizotinib
arm group type: Experimental
description: Subjects will receive 48 weeks (12 four-week cycles) of crizotinib 250 mg PO twice a day (BID). Subjects will be evaluated by routine bloodwork and physical exam every 4 weeks while they are receiving crizotinib and during follow up period.
intervention type: Drug
intervention name: Crizotinib
description: An anti-cancer drug acting as an anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibitor, used to treat non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in a gene called ALK.
Crizotinib will be provided as capsules containing 200 or 250 mg of study medication for oral administration.
arm group label: Crizotinib
other name: Xalkori
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Richard Carvajal, MD
role: Principal Investigator
affiliation: Associate Professor of Medicine at the Columbia University Medical Center
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.mskcc.org/
description: Memorial Sloan Kettering Cancer Center
responsible party type: Principal Investigator
investigator affiliation: Columbia University
investigator full name: Richard D. Carvajal
investigator title: Associate Professor of Medicine at the Columbia University Medical Center
mesh term: Melanoma
mesh term: Uveal Neoplasms
mesh term: Crizotinib
sharing ipd: Undecided
submitted: July 31, 2023
returned: August 24, 2023
submitted: August 29, 2023
returned: September 12, 2023