<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/NCT01713296</url>
  </required_header>
  <id_info>
    <org_study_id>CT/11.01</org_study_id>
    <nct_id>NCT01713296</nct_id>
  </id_info>
  <brief_title>Pazopanib in Relapsed and Refractory Small Cell Lung Cancer</brief_title>
  <official_title>A Phase II Trial of Pazopanib, in Relapsed and Refractory Small Cell Lung Cancer (SCLC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hellenic Oncology Research Group</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hellenic Oncology Research Group</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Investigators propose to study the single agent activity of pazopanib in a Phase II trial of&#xD;
      patients with relapsed or refractory small cell lung cancer. Because these patients have very&#xD;
      limited treatment options, use of an investigational agent in this patient population is&#xD;
      supported by current National Comprehensive Cancer Network guidelines. Using correlative&#xD;
      biologic studies to evaluate the anti angiogenic activity of pazopanib in the absence of&#xD;
      concomitant chemotherapy will allow us to delineate the responses due to this drug and the&#xD;
      effect on angiogenesis.&#xD;
&#xD;
      Pazopanib dose has been determined to 800 mg once daily per the initial recommended dose&#xD;
      approved by FDA and EMA, as monotherapy in advanced Renal Cell Carcinoma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Small cell lung cancer is a tumor that initially responds to chemotherapy and radiotherapy,&#xD;
      however, it is associated with very poor prognosis since the initial response is nearly&#xD;
      always followed by relapse and metastasis. The response to subsequent therapy is very limited&#xD;
      as is the duration of response in these patients. Patients with SCLC have high rates of&#xD;
      metastases at presentation suggesting that angiogenesis is particularly important in this&#xD;
      cancer, furthermore studies have shown that microvessel density and VEGF expression in SCLC&#xD;
      tumor samples correlate with development of metastases and poor prognosis. Furthermore VEGF&#xD;
      expression was the only factor that retained a significant inverse correlation with survival&#xD;
      when assessed in a multivariate analysis.&#xD;
&#xD;
      Pazopanib is a potent, small molecule competitive inhibitor of the tyrosine kinase activity&#xD;
      of (VEGFR 1), VEGFR 2, VEGFR 3, platelet derived growth factor (PDGF), and c kit, capable of&#xD;
      inhibiting downstream signalling from these receptors. The IC50 of pazopanib against VEGFR 2&#xD;
      is 10nm, and the IC50 against VEGFR 1 is &lt;50nm. Currently a number of studies is underway for&#xD;
      the evaluation of pazopanib in the treatment NSCLC. Administering pazopanib to patients with&#xD;
      relapsed SCLC offers an attractive choice in patients with very limited therapeutic choices.&#xD;
      The high rate of metastasis highlights the need for alternative treatments that act directly&#xD;
      on the growth and invasion of tumors and subsequent development of metastases, rather than&#xD;
      solely on cell proliferation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2011</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 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>Progression Free Rate</measure>
    <time_frame>2 Years</time_frame>
    <description>Patients will be assessed every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 168 weeks</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>3 years</time_frame>
    <description>Patients overall survival will be calculated from the date of the first chemotherapy cycle until the date of death from any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile</measure>
    <time_frame>Every 4 weeks</time_frame>
    <description>Patients will be evaluated on Day 1 of each cycle (cycle repeated every 4 weeks)up to two years from the date of first dose administration</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>SCLC</condition>
  <arm_group>
    <arm_group_label>Pazopanib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pazopanib</intervention_name>
    <arm_group_label>Pazopanib</arm_group_label>
    <other_name>Pazopanib: 800mg once a day for up to 2 years from date of first dose</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must provide written informed consent prior to performance of study-specific&#xD;
             procedures or assessments, and must be willing to comply with treatment and follow up&#xD;
             Procedures conducted as part of the patient's routine clinical management (e.g., blood&#xD;
             count, imaging study) and obtained prior to signing of informed consent may be&#xD;
             utilized for screening or baseline purposes provided these procedures are conducted as&#xD;
             specified in the protocol&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  Diagnosis of SCLC based on either histology or cytology (by FNA) with radiologically&#xD;
             confirmed progressive disease after first-line chemotherapy.&#xD;
&#xD;
          -  Presence of brain metastases is permitted if patient has completed treatment with&#xD;
             surgery and/or radiation more than four weeks prior to date of first dose of study&#xD;
             drug. Patients who have developed brain metastases following prophylactic cranial&#xD;
             irradiation will not be eligible for participation&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2&#xD;
&#xD;
          -  Measurable disease criteria according to RECIST 1.1&#xD;
&#xD;
          -  Only one prior chemotherapy regimen&#xD;
&#xD;
          -  Biologic material (blood samples, archived tissue) will be collected from consenting&#xD;
             patients for biomarker analysis before and/or during treatment with investigational&#xD;
             product&#xD;
&#xD;
          -  Adequate organ system function&#xD;
&#xD;
          -  Localised irradiation for SCLC is permitted as long as it was a minimum of 4 weeks&#xD;
             before entering the study; however, single-dose palliative radiation of bone&#xD;
             metastases for pain control may be allowed during the 4-week screening period&#xD;
&#xD;
          -  A female is eligible to enter and participate in this study if she is of:&#xD;
&#xD;
        Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),&#xD;
        including any female who has had: A hysterectomy, A bilateral oophorectomy (ovariectomy), A&#xD;
        bilateral tubal ligation, Is post-menopausal&#xD;
&#xD;
          -  Patients not using hormone replacement therapy (HRT) must have experienced total&#xD;
             cessation of menses for ≥ 1 year and be greater than 45 years in age, OR, in&#xD;
             questionable cases, have a follicle stimulating hormone (FSH) value &gt;40 mIU/mL and an&#xD;
             estradiol value &lt; 40pg/mL (&lt;140 pmol/L)&#xD;
&#xD;
          -  Patients using HRT must have experienced total cessation of menses for &gt;= 1 year and&#xD;
             be greater than 45 years of age OR have had documented evidence of menopause based on&#xD;
             FSH and estradiol concentrations prior to initiation of HRT Childbearing potential,&#xD;
             including any female who has had a negative serum pregnancy test within 2 weeks prior&#xD;
             to the first dose of study treatment, preferably as close to the first dose as&#xD;
             possible, and agrees to use adequate contraception. GSK acceptable contraceptive&#xD;
             methods, when used consistently and in accordance with both the product label and the&#xD;
             instructions of the physician, are as follow: Complete abstinence from sexual&#xD;
             intercourse for 14 days before exposure to investigational product, through the dosing&#xD;
             period, and for at least 21 days after the last dose of investigational product. Oral&#xD;
             contraceptive, either combined or progestogen alone. Injectable progestogen.Implants&#xD;
             of levonorgestre. Estrogenic vaginal ring. Percutaneous contraceptive patches.&#xD;
             Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure rate&#xD;
             of less than 1% per year. Male partner sterilization (vasectomy with documentation of&#xD;
             azoospermia) prior to the female subject's entry into the study, and this male is the&#xD;
             sole partner for that subject. Double barrier method: condom and an occlusive cap&#xD;
             (diaphragm or cervical/vault caps) with a vaginal spermicidal agent&#xD;
             (foam/gel/film/cream/suppository) Female subjects who are lactating should discontinue&#xD;
             nursing prior to the first dose of study drug and should refrain from nursing&#xD;
             throughout the treatment period and for 14 days following the last dose of study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior malignancy&#xD;
&#xD;
          -  Prior use of an investigational or licensed drug that targets VEGF or VEGF receptors&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may increase the risk for&#xD;
             gastrointestinal bleeding including, but not limited to:&#xD;
&#xD;
          -  Active peptic ulcer disease&#xD;
&#xD;
          -  Known intraluminal metastatic lesion/s with risk of bleeding&#xD;
&#xD;
          -  Inflammatory bowel disease (e.g. ulcerative colitis, Chrohn's disease), or other&#xD;
             gastrointestinal conditions with increased risk of perforation&#xD;
&#xD;
          -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess&#xD;
             within 28 days prior to beginning study treatment&#xD;
&#xD;
          -  Clinically significant gastrointestinal abnormalities that may affect absorption of&#xD;
             investigational product including, but not limited to: Malabsorption syndrome, Major&#xD;
             resection of the stomach or small bowel&#xD;
&#xD;
          -  Presence of uncontrolled infection.&#xD;
&#xD;
          -  Corrected QT interval (QTc) &gt; 480 msecs using Bazett's formula&#xD;
&#xD;
          -  History of any one or more of the following cardiovascular conditions within the past&#xD;
             6 months: Cardiac angioplasty or stenting, Myocardial infarction, Unstable angina,&#xD;
             Coronary artery bypass graft surgery, Symptomatic peripheral vascular disease, Class&#xD;
             III or IV congestive heart failure, as defined by the New York Heart Association&#xD;
             (NYHA)&#xD;
&#xD;
          -  Poorly controlled hypertension [defined as systolic blood pressure (SBP) of ≥140 mmHg&#xD;
             or diastolic blood pressure (DBP) of ≥ 90mmHg]&#xD;
&#xD;
          -  History of cerebrovascular accident including transient ischemic attack (TIA),&#xD;
             pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months&#xD;
&#xD;
          -  Prior major surgery or trauma within 28 days prior to first dose of study drug and/or&#xD;
             presence of any non-healing wound, fracture, or ulcer (procedures such as catheter&#xD;
             placement not considered to be major)&#xD;
&#xD;
          -  Evidence of active bleeding or bleeding diathesis&#xD;
&#xD;
          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels that&#xD;
             increase the risk of pulmonary haemorrhage, for example: Large protruding&#xD;
             endobronchial lesions in the main or lobar bronchi are excluded; however,&#xD;
             endobronchial lesions in the segmented bronchi are allowed, Lesions extensively&#xD;
             infiltrating the main or lobar bronchi are excluded; however, minor infiltrations in&#xD;
             the wall of the bronchi are allowed, Lesions infiltrating major pulmonary vessels&#xD;
             (contiguous tumour and vessels) are excluded; however, tumour touching but not&#xD;
             infiltrating (abutting) the vessels is acceptable (CT with contrast is strongly&#xD;
             recommended to evaluate such lesions)&#xD;
&#xD;
          -  Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 weeks of first dose of&#xD;
             study drug&#xD;
&#xD;
          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that&#xD;
             could interfere with subject's safety, provision of informed consent, or compliance to&#xD;
             study procedures&#xD;
&#xD;
          -  Unable or unwilling to discontinue use of prohibited medications for at least 14 days&#xD;
             or five half-lives of a drug (whichever is longer) prior to the first dose of study&#xD;
             drug and for the duration of the study&#xD;
&#xD;
          -  Treatment with any of the following anti-cancer therapies: radiation therapy, surgery&#xD;
             or tumor embolization within 14 days prior to the first dose of pazopanib or&#xD;
             chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal&#xD;
             therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the&#xD;
             first dose of pazopanib&#xD;
&#xD;
          -  Any ongoing toxicity from prior anti-cancer therapy that is &gt;Grade 1 and/or that is&#xD;
             progressing in severity, except alopecia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>&quot;Agioi Anargyroi&quot; Anticancer Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;IASO&quot; General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>401 Military Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Air Forces Military Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital of Crete, Dep of Medical Oncology Heraklion, Greece</name>
      <address>
        <city>Heraklion</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Metaxa's&quot; Anticancer Hospital of Piraeus, 1st Dep of Medical Oncology</name>
      <address>
        <city>Piraeus</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Papageorgiou&quot; Hospital of Thessaloniki</name>
      <address>
        <city>Thessaloniki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&quot;Theagenion&quot; Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology</name>
      <address>
        <city>Thessaloniki</city>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
  </location_countries>
  <verification_date>October 2015</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>October 22, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 24, 2012</study_first_posted>
  <last_update_submitted>October 7, 2015</last_update_submitted>
  <last_update_submitted_qc>October 7, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 8, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>SCLC</keyword>
  <keyword>2nd Line</keyword>
  <keyword>Relapsed or Refractory</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Small Cell Lung Carcinoma</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/NCT01713296
org study id: CT/11.01
nct id: NCT01713296
lead sponsor: 
has dmc: No
Investigators propose to study the single agent activity of pazopanib in a Phase II trial of
      patients with relapsed or refractory small cell lung cancer. Because these patients have very
      limited treatment options, use of an investigational agent in this patient population is
      supported by current National Comprehensive Cancer Network guidelines. Using correlative
      biologic studies to evaluate the anti angiogenic activity of pazopanib in the absence of
      concomitant chemotherapy will allow us to delineate the responses due to this drug and the
      effect on angiogenesis.

      Pazopanib dose has been determined to 800 mg once daily per the initial recommended dose
      approved by FDA and EMA, as monotherapy in advanced Renal Cell Carcinoma
Small cell lung cancer is a tumor that initially responds to chemotherapy and radiotherapy,
      however, it is associated with very poor prognosis since the initial response is nearly
      always followed by relapse and metastasis. The response to subsequent therapy is very limited
      as is the duration of response in these patients. Patients with SCLC have high rates of
      metastases at presentation suggesting that angiogenesis is particularly important in this
      cancer, furthermore studies have shown that microvessel density and VEGF expression in SCLC
      tumor samples correlate with development of metastases and poor prognosis. Furthermore VEGF
      expression was the only factor that retained a significant inverse correlation with survival
      when assessed in a multivariate analysis.

      Pazopanib is a potent, small molecule competitive inhibitor of the tyrosine kinase activity
      of (VEGFR 1), VEGFR 2, VEGFR 3, platelet derived growth factor (PDGF), and c kit, capable of
      inhibiting downstream signalling from these receptors. The IC50 of pazopanib against VEGFR 2
      is 10nm, and the IC50 against VEGFR 1 is <50nm. Currently a number of studies is underway for
      the evaluation of pazopanib in the treatment NSCLC. Administering pazopanib to patients with
      relapsed SCLC offers an attractive choice in patients with very limited therapeutic choices.
      The high rate of metastasis highlights the need for alternative treatments that act directly
      on the growth and invasion of tumors and subsequent development of metastases, rather than
      solely on cell proliferation.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Rate
time frame: 2 Years
description: Patients will be assessed every 8 weeks, from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 168 weeks
measure: Overall Survival
time frame: 3 years
description: Patients overall survival will be calculated from the date of the first chemotherapy cycle until the date of death from any cause
measure: Toxicity profile
time frame: Every 4 weeks
description: Patients will be evaluated on Day 1 of each cycle (cycle repeated every 4 weeks)up to two years from the date of first dose administration
arm group label: Pazopanib
arm group type: Experimental
intervention type: Drug
intervention name: Pazopanib
arm group label: Pazopanib
other name: Pazopanib: 800mg once a day for up to 2 years from date of first dose
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Greece
responsible party type: Sponsor
mesh term: Small Cell Lung Carcinoma