<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/NCT03022565</url>
  </required_header>
  <id_info>
    <org_study_id>20160653</org_study_id>
    <nct_id>NCT03022565</nct_id>
  </id_info>
  <brief_title>Vorinostat in Patients With Class 2 High Risk Uveal Melanoma</brief_title>
  <official_title>Proof of Concept Study of Vorinostat, A Histone Deacetylase Inhibitor, in Patients With Class 2 High Risk Uveal Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Miami Sylvester Comprehensive Cancer Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Miami</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This proof-of-concept study will evaluate the ability of vorinostat to induce the&#xD;
      transformation of Class 2 uveal melanoma cells into a cell phenotype that resembles normal&#xD;
      melanocytes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a proof of concept, single-center, open-label study of an FDA-approved drug,&#xD;
      vorinostat, a Histone deacetylase (HDAC) inhibitor, for patients with Class 2, high-risk&#xD;
      uveal melanoma with localized eye tumors. The primary aim is to test if vorinostat can&#xD;
      transform aggressive class 2 uveal melanoma cells into cells that look more like normal&#xD;
      melanocytes as observed in the laboratory. Uveal melanoma patients that meet the inclusion&#xD;
      criteria outlined in this protocol will be consented and asked to provide a fine needle&#xD;
      aspiration (FNA) biopsy of their uveal melanoma primary tumor. This biopsy will be submitted&#xD;
      for gene expression analysis to determine the phenotype of the tumor. A total of 10 patients&#xD;
      who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will&#xD;
      be treated with 400 mg of vorinostat daily for 15 days. On Day 15, patients will be asked to&#xD;
      provide a second FNA biopsy prior to receiving the standard of care local definitive therapy&#xD;
      either plaque radiotherapy or enucleation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Investigator Decision&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 2020</start_date>
  <completion_date type="Actual">January 29, 2020</completion_date>
  <primary_completion_date type="Actual">January 29, 2020</primary_completion_date>
  <phase>Early 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>Degree of transformation from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.</measure>
    <time_frame>From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks</time_frame>
    <description>The investigators will analyze gene expression results from fine needle aspirate biopsies performed at baseline prior to vorinostat therapy and post-treatment (on Day 15, after the planned 15 days of vorinostat therapy).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of patients whose tumors transformed from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.</measure>
    <time_frame>From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks</time_frame>
    <description>Through gene expression analysis, the investigators will determine the proportion of patients whose tumors transformed from a Class 2 phenotype into a cell phenotype that resembles normal melanocytes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Toxicity During Protocol Therapy</measure>
    <time_frame>Up to 1 Month Post-Treatment Completion</time_frame>
    <description>Rate of adverse events (AEs) and serious adverse events (SAEs) experienced by study participants during Vorinostat therapy and up to one month after Vorinostat treatment completion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor size before and after Vorinostat therapy</measure>
    <time_frame>From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks</time_frame>
    <description>Tumor size will be determined before and after Vorinostat therapy by B-Scan ultrasonography.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free survival (RFS)</measure>
    <time_frame>Up to 5 Years Post-Treatment Completion</time_frame>
    <description>Recurrence-Free Survival (RFS) in Study Participants. RFS is defined as the duration of time from start of treatment to time of disease recurrence or death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 Years Post-Treatment Completion</time_frame>
    <description>Overall Survival (OS) in Study Participants. OS is defined as the length of time from date of start of Vorinostat treatment to death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Specific Survival (DSS)</measure>
    <time_frame>Up to 5 Years Post-Treatment Completion</time_frame>
    <description>Disease Specific Survival (DSS) in Study Participants. DSS is defined as the time from start of Vorinostat treatment to death due to disease.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) before and after Vorinostat therapy.</measure>
    <time_frame>From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks</time_frame>
    <description>Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) will be measured at baseline (Day 1, before Vorinostat treatment) and post-treatment (day 15 after completion of Vorinostat therapy).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Uveal Melanoma</condition>
  <arm_group>
    <arm_group_label>Vorinostat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vorinostat:&#xD;
400 mg orally, once daily for 15 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vorinostat</intervention_name>
    <description>Study participants who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will be treated with 400 mg of Vorinostat daily for 15 days.</description>
    <arm_group_label>Vorinostat</arm_group_label>
    <other_name>Zolinza</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Uveal melanoma tumor determined by ophthalmic ultrasound or clinical assessment.&#xD;
&#xD;
          2. Class 2 uveal melanoma&#xD;
&#xD;
          3. No evidence of metastatic disease.&#xD;
&#xD;
          4. Age ≥18 years.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
&#xD;
          6. Life expectancy of greater than 3 months.&#xD;
&#xD;
          7. 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;
          8. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt;1,500 cells/mm³&#xD;
&#xD;
               -  Platelet count &gt;100,000/mm³&#xD;
&#xD;
               -  Hemoglobin &gt;10.0g/dL&#xD;
&#xD;
               -  Aspartate transaminase (AST) and/or Alanine transaminase (ALT) &lt; 3x upper limited&#xD;
                  of normal (ULN)&#xD;
&#xD;
               -  Total bilirubin &lt; 2x ULN&#xD;
&#xD;
               -  Hemoglobin A1C ≤ 5.7%&#xD;
&#xD;
               -  Alkaline phosphatase &lt; 3x ULN&#xD;
&#xD;
               -  Serum creatinine &lt; 2x ULN or a creatinine clearance &gt; 60 mL/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;
          9. 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 study drug&#xD;
             administration. Women of child-bearing potential must have a negative serum or urine&#xD;
             test at time of enrollment. Men treated or enrolled on this protocol must also agree&#xD;
             to use adequate contraception prior to the study, for the duration of study therapy,&#xD;
             and 4 months after completion of study drug administration.&#xD;
&#xD;
         10. Willingness to comply with all the visits and procedures (including providing all&#xD;
             biological specimens) as required by the protocol and the informed consent form (ICF).&#xD;
&#xD;
         11. Ability to understand the investigational nature, potential risks and benefits of the&#xD;
             research study and to provide valid written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Definitive therapy of the primary uveal melanoma by either surgery or radiotherapy&#xD;
&#xD;
          2. 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;
          3. Any major surgery or extensive radiotherapy, chemotherapy with delayed toxicity,&#xD;
             biologic therapy, or immunotherapy within 21 days prior to initiation of study&#xD;
             therapy.&#xD;
&#xD;
          4. History of prior vorinostat use.&#xD;
&#xD;
          5. Use of other investigational drugs within 28 days&#xD;
&#xD;
          6. Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs&#xD;
             chemically related to vorinostat (i.e. HDAC inhibitor hydroxamates such as&#xD;
             panobinostat and belinostat).&#xD;
&#xD;
          7. A QT interval corrected (QTc) for heart rate using the Bazett's formula (QTcB) ≥ 480&#xD;
             msec. Concurrent administration of vorinostat and agents that can cause QTc&#xD;
             prolongation is not permitted.&#xD;
&#xD;
          8. Concurrent administration of vorinostat and other HDAC inhibitors is not permitted due&#xD;
             to the increased risk of thrombocytopenia and gastrointestinal bleeding.&#xD;
&#xD;
          9. Patients on combination antiretroviral therapy are ineligible because of the potential&#xD;
             for pharmacokinetic interactions with vorinostat.&#xD;
&#xD;
         10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infections, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             the study requirements.&#xD;
&#xD;
         11. History of pulmonary embolism (PT) or deep-vein thrombosis (DVT)&#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>J. William Harbour, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>December 21, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <last_update_submitted>February 4, 2020</last_update_submitted>
  <last_update_submitted_qc>February 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">February 6, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>J. William Harbour, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Uveal Melanoma</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>Vorinostat</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/NCT03022565
org study id: 20160653
nct id: NCT03022565
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This proof-of-concept study will evaluate the ability of vorinostat to induce the
      transformation of Class 2 uveal melanoma cells into a cell phenotype that resembles normal
      melanocytes.
This is a proof of concept, single-center, open-label study of an FDA-approved drug,
      vorinostat, a Histone deacetylase (HDAC) inhibitor, for patients with Class 2, high-risk
      uveal melanoma with localized eye tumors. The primary aim is to test if vorinostat can
      transform aggressive class 2 uveal melanoma cells into cells that look more like normal
      melanocytes as observed in the laboratory. Uveal melanoma patients that meet the inclusion
      criteria outlined in this protocol will be consented and asked to provide a fine needle
      aspiration (FNA) biopsy of their uveal melanoma primary tumor. This biopsy will be submitted
      for gene expression analysis to determine the phenotype of the tumor. A total of 10 patients
      who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will
      be treated with 400 mg of vorinostat daily for 15 days. On Day 15, patients will be asked to
      provide a second FNA biopsy prior to receiving the standard of care local definitive therapy
      either plaque radiotherapy or enucleation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Degree of transformation from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
description: The investigators will analyze gene expression results from fine needle aspirate biopsies performed at baseline prior to vorinostat therapy and post-treatment (on Day 15, after the planned 15 days of vorinostat therapy).
measure: Proportion of patients whose tumors transformed from a class 2 phenotype into a cell phenotype that resembles normal melanocytes.
time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
description: Through gene expression analysis, the investigators will determine the proportion of patients whose tumors transformed from a Class 2 phenotype into a cell phenotype that resembles normal melanocytes.
measure: Toxicity During Protocol Therapy
time frame: Up to 1 Month Post-Treatment Completion
description: Rate of adverse events (AEs) and serious adverse events (SAEs) experienced by study participants during Vorinostat therapy and up to one month after Vorinostat treatment completion.
measure: Tumor size before and after Vorinostat therapy
time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
description: Tumor size will be determined before and after Vorinostat therapy by B-Scan ultrasonography.
measure: Recurrence-free survival (RFS)
time frame: Up to 5 Years Post-Treatment Completion
description: Recurrence-Free Survival (RFS) in Study Participants. RFS is defined as the duration of time from start of treatment to time of disease recurrence or death, whichever occurs first.
measure: Overall survival (OS)
time frame: Up to 5 Years Post-Treatment Completion
description: Overall Survival (OS) in Study Participants. OS is defined as the length of time from date of start of Vorinostat treatment to death.
measure: Disease Specific Survival (DSS)
time frame: Up to 5 Years Post-Treatment Completion
description: Disease Specific Survival (DSS) in Study Participants. DSS is defined as the time from start of Vorinostat treatment to death due to disease.
measure: Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) before and after Vorinostat therapy.
time frame: From Baseline to 15 Days of Protocol Therapy, Up to 4 Weeks
description: Global histone acetylation levels in peripheral blood mononuclear cells (PBMCs) will be measured at baseline (Day 1, before Vorinostat treatment) and post-treatment (day 15 after completion of Vorinostat therapy).
arm group label: Vorinostat
arm group type: Experimental
description: Vorinostat:
400 mg orally, once daily for 15 days.
intervention type: Drug
intervention name: Vorinostat
description: Study participants who meet the criteria of Class 2 uveal melanoma and no radiologic evidence of metastases will be treated with 400 mg of Vorinostat daily for 15 days.
arm group label: Vorinostat
other name: Zolinza
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: J. William Harbour, MD
role: Principal Investigator
affiliation: University of Miami
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: J. William Harbour, MD
investigator title: Professor
mesh term: Melanoma
mesh term: Uveal Neoplasms
mesh term: Vorinostat
sharing ipd: No