<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/NCT01716416</url>
  </required_header>
  <id_info>
    <org_study_id>201211110</org_study_id>
    <nct_id>NCT01716416</nct_id>
  </id_info>
  <brief_title>Pazopanib Plus Cetuximab for Incurable Head and Neck Squamous Cell Carcinoma (HNSCC)</brief_title>
  <acronym>HNSCC</acronym>
  <official_title>A Phase I Trial of Pazopanib Suspension Plus Cetuximab in Patients With Incurable Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</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 phase I trial studies the side effects and best dose of pazopanib hydrochloride&#xD;
      (pazopanib) when given together with cetuximab in treating patients with incurable recurrent&#xD;
      or metastatic head and neck cancer. Pazopanib may stop the growth of cancer by blocking blood&#xD;
      flow to the tumor. Pazopanib may also block some of the enzymes needed for cell growth.&#xD;
      Cetuximab is a monoclonal antibody that blocks the ability of some tumor cells to grow and&#xD;
      spread. Giving pazopanib with cetuximab may provide a more effective treatment for patients&#xD;
      with advanced head and neck cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 31, 2013</start_date>
  <completion_date type="Actual">August 31, 2017</completion_date>
  <primary_completion_date type="Actual">July 31, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerable dose (MTD) of pazopanib suspension when combined with fixed dose cetuximab in patients with incurable HNSCC.</measure>
    <time_frame>9 weeks (completion of all patients in part 1 of study through 1st cycle)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Early Adverse events</measure>
    <time_frame>8 weeks</time_frame>
    <description>Graded by NCI-CTC criteria version 4 and described in a frequency distribution analysis for the first 8 weeks of pazopanib and cetuximab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Late adverse events</measure>
    <time_frame>Weeks 8 through 16</time_frame>
    <description>Graded by NCI-CTC criteria version 4 and described in a frequency distribution analysis for subsequent interval (after first 8 weeks of therapy) of receiving pazopanib and cetuximab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anatomic tumor response</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed by CT and clinical exam</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall metabolic response</measure>
    <time_frame>8 weeks</time_frame>
    <description>Assessed by FDG-PET</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>8 weeks</time_frame>
    <description>CR+PR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of overall response</measure>
    <time_frame>8 weeks</time_frame>
    <description>Time from CR or PR until relapse</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response rates in patients treated with MTD</measure>
    <time_frame>8 weeks</time_frame>
    <description>According to RECIST criteria</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Squamous Cell Carcinoma of the Head and Neck</condition>
  <arm_group>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pazopanib 200 mg PO QD&#xD;
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pazopanib 400 mg PO QD&#xD;
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pazopanib 600 mg PO QD&#xD;
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pazopanib 800 mg PO QD&#xD;
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2 Dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pazopanib (dose to be determined in Part 1 of study) mg PO QD&#xD;
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pazopanib</intervention_name>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_label>Dose Level 4</arm_group_label>
    <arm_group_label>Part 2 Dose</arm_group_label>
    <other_name>Votrient®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cetuximab</intervention_name>
    <arm_group_label>Dose Level 1</arm_group_label>
    <arm_group_label>Dose Level 2</arm_group_label>
    <arm_group_label>Dose Level 3</arm_group_label>
    <arm_group_label>Dose Level 4</arm_group_label>
    <arm_group_label>Part 2 Dose</arm_group_label>
    <other_name>Erbitux®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient must have histologically confirmed diagnosis of incurable metastatic or&#xD;
             recurrent head and neck squamous cell carcinoma&#xD;
&#xD;
          -  Patient must have measurable disease defined as lesions that can be accurately&#xD;
             measured in at least one dimension (longest diameter to be recorded) as ≥10 mm with CT&#xD;
             scan, as ≥20 mm by chest x-ray, or ≥10 mm with calipers by clinical exam (Expanded&#xD;
             Cohort only; patients without measurable disease by RECIST 1.1 criteria but with&#xD;
             evaluable disease will be eligible for the dose-finding phase).&#xD;
&#xD;
          -  Patient must be ≥ 18 years of age.&#xD;
&#xD;
          -  Patient must have an ECOG performance status 0-1&#xD;
&#xD;
          -  Patient must have normal bone marrow and organ function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  Platelets ≥ 100,000/mcL&#xD;
&#xD;
               -  Hemoglobin ≥ 9.0 g/dL&#xD;
&#xD;
               -  INR ≤ 1.2 x IULN; patients receiving anticoagulant therapy are eligible if their&#xD;
                  INR is stable and within the recommended range for the desired level of&#xD;
                  anticoagulation&#xD;
&#xD;
               -  aPTT ≤ 1.2 x IULN&#xD;
&#xD;
               -  Corrected QT interval (QTc) &lt; 480 msecs&#xD;
&#xD;
               -  Total bilirubin ≤ 1.5 x IULN&#xD;
&#xD;
               -  AST(SGOT) ≤ 2.5 x IULN and ALT(SGPT) ≤ 2.5 x IULN&#xD;
&#xD;
               -  Creatinine ≤ 1.5 mg/dL OR Creatinine clearance ≥ 50 mL/min/1.73 m2 for patients&#xD;
                  with creatinine levels &gt; 1.5 mg/dL&#xD;
&#xD;
               -  Urine protein to creatinine ratio (UPC) &lt; 1; if UPC ≥ 1, then a 24-hour urine&#xD;
                  protein must be assessed; patients must have a 24-hour urine protein value &lt; 1 g&#xD;
                  to be eligible&#xD;
&#xD;
          -  Women of childbearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) beginning 14 days prior to&#xD;
             first dose of pazopanib, through the dosing period, and for at least 28 days after the&#xD;
             last dose of pazopanib.&#xD;
&#xD;
          -  Patient must be able to understand and willing to sign an IRB approved written&#xD;
             informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  For the expanded cohort only, patient must not have had prior therapy with an&#xD;
             EGFR-specific monoclonal antibody or EGFR-specific TKI for treatment of incurable&#xD;
             HNSCC. Prior therapy with an EGFR-specific monoclonal antibody as part of the&#xD;
             definitive treatment of curable HNSCC is acceptable if this occurred more than 3&#xD;
             months prior to study enrollment. For the dose-finding cohorts, prior EGFR-specific&#xD;
             therapy in the incurable setting is allowed.&#xD;
&#xD;
          -  Patient must not have had radiation therapy, minor surgery, or tumor embolization with&#xD;
             14 days prior to the first dose of pazopanib.&#xD;
&#xD;
          -  Patient must not have had chemotherapy, immunotherapy, biologic therapy, hormonal&#xD;
             therapy, or investigational therapy within 14 days or 5 half-lives of the drug prior&#xD;
             to the first dose of pazopanib. For patients enrolling in the phase I portion of this&#xD;
             study, this requirement does not apply to prior treatment with cetuximab.&#xD;
&#xD;
          -  Patient must not have prior major surgery, trauma, presence of any non-healing wound,&#xD;
             fracture, or ulcer within 28 days prior to first dose of study drug.&#xD;
&#xD;
          -  Patient must not have a history of other malignancy ≤ 2 years previous with the&#xD;
             exception of completely resected non-melanomatous skin carcinoma or successfully&#xD;
             treated in situ carcinoma.&#xD;
&#xD;
          -  Patient must not be receiving any medication that is a strong CYP3A4 inhibitor&#xD;
             beginning 14 days prior to first dose of study drug. Strong CYP3A4 inhibitors include&#xD;
             (but are not limited to): antibiotics such as clarithromycin, telithromycin,&#xD;
             troleandromycin; protease inhibitors such as ritonavir, indinavir, saquinavir,&#xD;
             nelfinavir, lopinavir; antifungals such as itraconazole, ketoconazole, voriconazole;&#xD;
             and antidepressants such as nefazodone.&#xD;
&#xD;
          -  Patient must not be receiving any other investigational agents.&#xD;
&#xD;
          -  Patient must not be experiencing any ongoing toxicity from prior anti-cancer therapy&#xD;
             that is &gt; grade 1 or that is progressing in severity, except alopecia.&#xD;
&#xD;
          -  Patient must not have a history of or clinical evidence of central nervous system&#xD;
             metastases or leptomeningeal carcinomatosis, except for individuals who have had&#xD;
             previously-treated CNS metastases, are asymptomatic, and have had no requirement for&#xD;
             steroids or anti-seizure medications for 6 months prior to first dose of pazopanib.&#xD;
&#xD;
          -  Patient must not have a history of allergic reactions attributed to compounds of&#xD;
             similar chemical or biologic composition to pazopanib, cetuximab, or other agents used&#xD;
             in the study.&#xD;
&#xD;
          -  Patient must not have any clinically significant gastrointestinal abnormality that may&#xD;
             increase the risk of GI bleeding including, but not limited to, active peptic ulcer&#xD;
             disease, known intraluminal metastatic lesions with risk of bleeding, inflammatory&#xD;
             bowel disease (e.g., ulcerative colitis, Crohn's disease), other GI conditions with&#xD;
             increased risk of perforation, history of abdominal fistula or GI perforation or&#xD;
             intra-abdominal abscess within 28 days prior to beginning study treatment.&#xD;
&#xD;
          -  Patient must not have any clinically significant abnormality that may affect&#xD;
             absorption of investigational product including, but not limited to, malabsorption&#xD;
             syndrome or major resection of the stomach or small bowel.&#xD;
&#xD;
          -  Patient must not have an uncontrolled intercurrent illness within the 6 months prior&#xD;
             to study entry including, but not limited to, ongoing or active infection, Class III&#xD;
             or IV congestive heart failure (as defined by the New York Heart Association (NYHA)),&#xD;
             unstable angina pectoris, cardiac arrhythmia, myocardial infarction, cardiac&#xD;
             angioplasty or stenting, coronary artery bypass graft surgery, symptomatic peripheral&#xD;
             vascular disease, or psychiatric illness/social situations that would limit compliance&#xD;
             with study requirements.&#xD;
&#xD;
          -  Patient must not have poorly controlled hypertension (defined as systolic blood&#xD;
             pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg). Initiation or&#xD;
             adjustment of antihypertensive medications is permitted prior to study entry. Blood&#xD;
             pressure must be re-assessed on two occasions that are separated by a minimum of one&#xD;
             hour; on each of these occasions, the mean (of 3 readings) from each assessment must&#xD;
             be &lt; 140/90 mmHg for a patient to be eligible for this study.&#xD;
&#xD;
          -  Patient must not have a history of cerebrovascular accident including transient&#xD;
             ischemic attack within the past 6 months. Patients with recent deep venous thrombosis&#xD;
             or pulmonary embolism who have been treated with therapeutic anti-coagulating agents&#xD;
             for at least 6 weeks are eligible as long as INR is stable.&#xD;
&#xD;
          -  Patient must not have evidence of active bleeding or bleeding diathesis.&#xD;
&#xD;
          -  Patient must not have any known endobronchial lesions and/or lesions infiltrating&#xD;
             major pulmonary vessels.&#xD;
&#xD;
          -  Patient must not experience hemoptysis in excess of 2.5 mL within 8 weeks prior to the&#xD;
             first dose of pazopanib.&#xD;
&#xD;
          -  Patient must not be pregnant and/or breastfeeding. Patient must have a negative serum&#xD;
             pregnancy test within 14 days of study entry.&#xD;
&#xD;
          -  Patient must not be known to be HIV-positive on combination antiretroviral because of&#xD;
             the potential for pharmacokinetic interactions with pazopanib. In addition, these&#xD;
             patients are at increased risk of lethal infections when treated with&#xD;
             marrow-suppressive therapy. Appropriate studies will be undertaken in patients&#xD;
             receiving combination antiretroviral therapy when indicated.&#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>Douglas Adkins, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>April 12, 2019</last_update_submitted>
  <last_update_submitted_qc>April 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2019</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>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</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/NCT01716416
org study id: 201211110
nct id: NCT01716416
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This phase I trial studies the side effects and best dose of pazopanib hydrochloride
      (pazopanib) when given together with cetuximab in treating patients with incurable recurrent
      or metastatic head and neck cancer. Pazopanib may stop the growth of cancer by blocking blood
      flow to the tumor. Pazopanib may also block some of the enzymes needed for cell growth.
      Cetuximab is a monoclonal antibody that blocks the ability of some tumor cells to grow and
      spread. Giving pazopanib with cetuximab may provide a more effective treatment for patients
      with advanced head and neck cancer.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerable dose (MTD) of pazopanib suspension when combined with fixed dose cetuximab in patients with incurable HNSCC.
time frame: 9 weeks (completion of all patients in part 1 of study through 1st cycle)
measure: Early Adverse events
time frame: 8 weeks
description: Graded by NCI-CTC criteria version 4 and described in a frequency distribution analysis for the first 8 weeks of pazopanib and cetuximab
measure: Late adverse events
time frame: Weeks 8 through 16
description: Graded by NCI-CTC criteria version 4 and described in a frequency distribution analysis for subsequent interval (after first 8 weeks of therapy) of receiving pazopanib and cetuximab
measure: Anatomic tumor response
time frame: 8 weeks
description: Assessed by CT and clinical exam
measure: Overall metabolic response
time frame: 8 weeks
description: Assessed by FDG-PET
measure: Overall response rate
time frame: 8 weeks
description: CR+PR
measure: Duration of overall response
time frame: 8 weeks
description: Time from CR or PR until relapse
measure: Best overall response rates in patients treated with MTD
time frame: 8 weeks
description: According to RECIST criteria
arm group label: Dose Level 1
arm group type: Experimental
description: Pazopanib 200 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2
arm group label: Dose Level 2
arm group type: Experimental
description: Pazopanib 400 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2
arm group label: Dose Level 3
arm group type: Experimental
description: Pazopanib 600 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2
arm group label: Dose Level 4
arm group type: Experimental
description: Pazopanib 800 mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2
arm group label: Part 2 Dose
arm group type: Experimental
description: Pazopanib (dose to be determined in Part 1 of study) mg PO QD
Cetuximab 400 mg/m^2 (cycle 1 week 1 only) followed by weekly maintenance doses of 250 mg/m^2
intervention type: Drug
intervention name: Pazopanib
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
arm group label: Dose Level 4
arm group label: Part 2 Dose
other name: Votrient®
intervention type: Drug
intervention name: Cetuximab
arm group label: Dose Level 1
arm group label: Dose Level 2
arm group label: Dose Level 3
arm group label: Dose Level 4
arm group label: Part 2 Dose
other name: Erbitux®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Douglas Adkins, M.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Cetuximab
sharing ipd: No