<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/NCT01678105</url>
  </required_header>
  <id_info>
    <org_study_id>OCOG-2012-DOVE</org_study_id>
    <nct_id>NCT01678105</nct_id>
  </id_info>
  <brief_title>A Phase II Study of Dovitinib in Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands</brief_title>
  <acronym>DOVE</acronym>
  <official_title>A Phase II Study of DOVitinib in REcurrent and/or Metastatic Adenoid Cystic Carcinoma of the Salivary Glands (DOVE)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ontario Clinical Oncology Group (OCOG)</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Ontario Clinical Oncology Group (OCOG)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a non-randomized, phase II, open label study of dovitinib in patients with&#xD;
      progressive, recurrent and/or metastatic adenoid cystic carcinoma (ACC). The primary purpose&#xD;
      of this study is to assess the anti-cancer effects of dovitinib in this population in order&#xD;
      to evaluate whether dovitinib is worthy of further study in patients with progressive ACC.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Clinical Benefit Rate</measure>
    <time_frame>2 years</time_frame>
    <description>The primary outcome measure is the clinical benefit rate, defined as an objective response (complete [CR] or partial [PR]) or stable disease [SD] of ≥6 months duration according to the RECIST version 1.1 criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>From the date the patient first receives study medication to the date of death or date of progression according to RECIST or symptomatic deterioration; estimated to be after 12 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From the date the patient first receives study medication to the date of death; patients will be followed up for survival for up to 2 years after disease progression</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability</measure>
    <time_frame>From the date the patient first receives study medication to the date the patient completes the study; patients will be followed up for survival for up to 2 years after disease progression</time_frame>
    <description>Patients will be evaluated for toxicity. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occuring, serious and severe events of interest.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Recurrent Adenoid Cystic Carcinoma of the Salivary Glands</condition>
  <condition>Metastatic Adenoid Cystic Carcinoma of the Salivary Glands</condition>
  <condition>Salivary Gland Cancers</condition>
  <condition>ACC</condition>
  <arm_group>
    <arm_group_label>Dovitinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dovitinib 500 mg PO OD (5 days on, 2 days off); Each cycle = 28 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dovitinib</intervention_name>
    <description>Treatment continued until Disease Progression, Toxicity, or patient withdrawal</description>
    <arm_group_label>Dovitinib</arm_group_label>
    <other_name>TKI258</other_name>
    <other_name>RTK Inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed ACC of major or minor salivary glands.&#xD;
&#xD;
          -  Recurrent and/or metastatic disease deemed progressive that is not amenable to surgery&#xD;
             or curative radiotherapy.&#xD;
&#xD;
          -  Measurable disease according to the Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST, version 1.1), defined as at least one lesion that can be accurately measured&#xD;
             in at least one dimension (longest diameter in the plane of measurement is to be&#xD;
             recorded) with a minimum size of:&#xD;
&#xD;
               -  &gt; 10 mm by CT scan (CT scan slice thickness no greater than 5 mm).&#xD;
&#xD;
               -  &gt; 10 mm caliper measurement by clinical exam (lesion which cannot be accurately&#xD;
                  measured with calipers should be recorded as non-measurable).&#xD;
&#xD;
               -  &gt; 20 mm by chest X-ray Malignant lymph nodes: To be considered pathologically&#xD;
                  enlarged and measurable, a lymph node must be &gt;15mm in short axis when assessed&#xD;
                  by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).&#xD;
&#xD;
          -  Progressive disease, defined as one of the following occurring within 12 months of&#xD;
             study entry:&#xD;
&#xD;
             i) at least a 10% increase in radiologically or clinically measurable disease; ii)&#xD;
             appearance of one or more new lesions, or iii) deterioration in clinical status.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Less than 18 years of age.&#xD;
&#xD;
          -  Life expectancy &lt; 12 weeks.&#xD;
&#xD;
          -  ECOG performance status &gt; 2.&#xD;
&#xD;
          -  Known brain metastases.&#xD;
&#xD;
          -  Treatment with chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas&#xD;
             or mitomycin C) prior to entering the study or those who have not recovered from&#xD;
             adverse events due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Major surgery within 4 weeks prior to entering the study.&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to dovitinib.&#xD;
&#xD;
          -  Taking medications that are potent CYP3A4 inducers or inhibitors (dovitinib is&#xD;
             metabolized primarily by the CYP3A4 liver enzyme, every effort should be made to&#xD;
             switch patients taking such agents or substances to other medications).&#xD;
&#xD;
          -  History of cardiac dysfunction with an ECHO or MUGA scan outside the institutional&#xD;
             range of normal.&#xD;
&#xD;
          -  QTc prolongation (defined as a QTc interval &gt; 500 msec) or other significant ECG&#xD;
             abnormalities.&#xD;
&#xD;
          -  Poorly controlled hypertension (systolic blood pressure of ≥ 140 mmHg or diastolic&#xD;
             blood pressure of ≥ 90 mmHg).&#xD;
&#xD;
          -  Any abnormal organ and marrow function as defined below:&#xD;
&#xD;
               -  Leukocytes &lt;3,000/microL&#xD;
&#xD;
               -  Absolute neutrophil count &lt;1,500/microL&#xD;
&#xD;
               -  Platelets &lt;100,000/microL&#xD;
&#xD;
               -  Total bilirubin &gt;1.5X institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  AST(SGOT) / ALT(SGPT) &gt;2.5X institutional ULN&#xD;
&#xD;
               -  Amylase/lipase outside normal institutional limits&#xD;
&#xD;
               -  Serum creatinine &gt;1.5X ULN&#xD;
&#xD;
               -  Creatinine clearance &lt;60mL/min/1.73 m2 for patients with creatinine levels above&#xD;
                  institutional normal&#xD;
&#xD;
          -  Required use of therapeutic doses of coumarin-derivative anticoagulants such as&#xD;
             warfarin, although doses of up to 2mg daily are permitted for prophylaxis of&#xD;
             thrombosis. Note: Low molecular weight heparin is permitted provided the patient's PT&#xD;
             INR is ≤ 1.5.&#xD;
&#xD;
          -  Pre-existing condition (e.g., gastrointestinal tract disease), resulting in an&#xD;
             inability to take oral medication or a requirement for IV alimentation, prior surgical&#xD;
             procedures affecting absorption, or active peptic ulcer disease that impairs their&#xD;
             ability to swallow and retain dovitinib tablets.&#xD;
&#xD;
          -  Pre-existing thyroid abnormality with an inability to maintain thyroid function in the&#xD;
             normal range with medication.&#xD;
&#xD;
          -  Any of the following conditions:&#xD;
&#xD;
               -  Serious or non-healing wound, ulcer, or bone fracture,&#xD;
&#xD;
               -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal&#xD;
                  abscess within 28 days of treatment,&#xD;
&#xD;
               -  History of cerebrovascular accident (CVA) or transient ischemic attack (TIA)&#xD;
                  within 12 months prior to study entry,&#xD;
&#xD;
               -  History of pulmonary embolism within the past 12 months,&#xD;
&#xD;
               -  History of myocardial infarction, cardiac arrhythmia, stable/unstable angina,&#xD;
                  symptomatic congestive heart failure, or coronary/peripheral artery bypass graft&#xD;
                  or stenting within 12 months prior to study entry,&#xD;
&#xD;
               -  NYHA Class III or IV heart failure as defined by the NYHA functional&#xD;
                  classification system.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infections, HIV-positive patients on combination antiretroviral therapy.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements.&#xD;
&#xD;
          -  Receiving any other investigational agent(s).&#xD;
&#xD;
          -  Inability to understand or unable to provide written informed consent.&#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>Sebastien Hotte, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Juravinski Cancer Centre</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark Levine, MD</last_name>
    <role>Study Director</role>
    <affiliation>Ontario Clinical Oncology Group (OCOG)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Greg Pond, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ontario Clinical Oncology Group (OCOG)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tom Baker Cancer Centre</name>
      <address>
        <city>Calgary</city>
        <state>Ontario</state>
        <zip>T2N 4N2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juravinski Cancer Centre</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>London Health Sciences Centre</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 4L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ottawa Hospital Regional Cancer Centre</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>August 23, 2012</study_first_submitted>
  <study_first_submitted_qc>August 29, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <last_update_submitted>September 16, 2015</last_update_submitted>
  <last_update_submitted_qc>September 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 17, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Recurrent Adenoid Cystic Carcinoma of the Salivary Glands</keyword>
  <keyword>Metastatic Adenoid Cystic Carcinoma of the Salivary Glands</keyword>
  <keyword>Salivary Gland Cancers</keyword>
  <keyword>ACC</keyword>
  <keyword>Dovitinib</keyword>
  <keyword>TKI258</keyword>
  <keyword>RTK Inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Salivary Gland Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Adenoid Cystic</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <!-- 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/NCT01678105
org study id: OCOG-2012-DOVE
nct id: NCT01678105
lead sponsor: 
collaborator: 
has dmc: Yes
This is a non-randomized, phase II, open label study of dovitinib in patients with
      progressive, recurrent and/or metastatic adenoid cystic carcinoma (ACC). The primary purpose
      of this study is to assess the anti-cancer effects of dovitinib in this population in order
      to evaluate whether dovitinib is worthy of further study in patients with progressive ACC.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Clinical Benefit Rate
time frame: 2 years
description: The primary outcome measure is the clinical benefit rate, defined as an objective response (complete [CR] or partial [PR]) or stable disease [SD] of ≥6 months duration according to the RECIST version 1.1 criteria.
measure: Progression Free Survival
time frame: From the date the patient first receives study medication to the date of death or date of progression according to RECIST or symptomatic deterioration; estimated to be after 12 weeks of treatment
measure: Overall Survival
time frame: From the date the patient first receives study medication to the date of death; patients will be followed up for survival for up to 2 years after disease progression
measure: Safety and tolerability
time frame: From the date the patient first receives study medication to the date the patient completes the study; patients will be followed up for survival for up to 2 years after disease progression
description: Patients will be evaluated for toxicity. Frequency and severity of adverse events will be tabulated using counts and proportions detailing frequently occuring, serious and severe events of interest.
arm group label: Dovitinib
arm group type: Experimental
description: Dovitinib 500 mg PO OD (5 days on, 2 days off); Each cycle = 28 days
intervention type: Drug
intervention name: Dovitinib
description: Treatment continued until Disease Progression, Toxicity, or patient withdrawal
arm group label: Dovitinib
other name: TKI258
other name: RTK Inhibitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sebastien Hotte, MD
role: Principal Investigator
affiliation: Juravinski Cancer Centre
last name: Mark Levine, MD
role: Study Director
affiliation: Ontario Clinical Oncology Group (OCOG)
last name: Greg Pond, PhD
role: Principal Investigator
affiliation: Ontario Clinical Oncology Group (OCOG)
facility: 
facility: 
facility: 
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Salivary Gland Neoplasms
mesh term: Carcinoma, Adenoid Cystic
mesh term: Recurrence