<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/NCT02216916</url>
  </required_header>
  <id_info>
    <org_study_id>4-2013-0794</org_study_id>
    <nct_id>NCT02216916</nct_id>
  </id_info>
  <brief_title>Phase II Trial of HM781-36B in Patients With Metastatic/Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) After Failure of or Unfit for Platinum-containing Therapy</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yonsei University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Yonsei University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Head and neck cancer is the sixth most common cancer and more than 650,000 new cases are&#xD;
      diagnosed each year worldwide. About 60% of the HNSCC patients present with unresectable&#xD;
      locally advanced disease at diagnosis and treated with multimodality approach. Despite such&#xD;
      approach, majority (70%) of patients develop local or/and regional recurrences. Additional&#xD;
      10% of patients present with distant metastasis at diagnosis. Most patients with recurrent or&#xD;
      metastatic disease are treated with single agent chemotherapy, combination chemotherapy or&#xD;
      targeted therapies.&#xD;
&#xD;
      Despite its public health magnitude, HNSCC in Asian countries has received a limited&#xD;
      attention for the drug development and cancer-related research. In fact, HNSCC ranked 7th&#xD;
      among men and 10th among women by incidence in China, the largest producer and consumer of&#xD;
      tobacco and alcohol. Recently, Chen et al. documented a 1:1:2 subset distribution for cancers&#xD;
      of oral cavity, pharynx, and larynx in China, similar to the distribution reported in Korea&#xD;
      but quite different from the general distribution of 5:2:3 in whites. Ethnic disparities in&#xD;
      HNSCC also include its prognosis and this is partly explained by HPV-active disease ratio and&#xD;
      genetic factors. Therefore, there is a strong need for an additional research in patients&#xD;
      with HNSCC in Asia.&#xD;
&#xD;
      Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to&#xD;
      poor prognosis in patients with HNSCC. The association between EGFR-activated signaling&#xD;
      pathways and tumor cell survival are well documented in many studies. EGFR targeting&#xD;
      strategies showed clinical anti-tumor efficacy in patients with HNSCC, especially with&#xD;
      monoclonal antibody, cetuximab. In the Extreme study, it was shown that the addition of&#xD;
      cetuximab to platinum-5-FU significantly prolonged the median overall survival from 7.4&#xD;
      months to 10.1 months compared to platinum-5FU alone in the first-line setting.&#xD;
&#xD;
      HM781-36B is a irreversible pan-HER inhibitor. In preclinical studies, HM781-36B has much&#xD;
      lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations and&#xD;
      produces tumor growth inhibition in gefitinib-resistant xenografts. A phase I trial of&#xD;
      HM781-36B in patients with advanced solid tumors showed clinically significant anti-tumor&#xD;
      activity and a phase II trials of HM781-36B in patients with non-small cell lung cancer and&#xD;
      advanced gastric cancer are currently ongoing.&#xD;
&#xD;
      We suggest a phase II trial of HM781-36B in patients with recurrent or metastatic HNSCC who&#xD;
      are resistant or ineligible/intolerant to platinum-based chemotherapy. The aim of current&#xD;
      trial is to evaluate the antitumor efficacy and safety profile of HM781-36B and to identify&#xD;
      biomarker to predict the tumor response to HM781-36B.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">July 2019</completion_date>
  <primary_completion_date type="Anticipated">July 2019</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>Response rate</measure>
    <time_frame>28th day of 1st chemotherapy cycle</time_frame>
    <description>Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria 1.1 (RECIST 1.1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response</measure>
    <time_frame>1years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>1years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival</measure>
    <time_frame>1years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>1years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Toxicity profile</measure>
    <time_frame>1years</time_frame>
    <description>Overall safety profile and toleration of HM781-36B will be characterized by type, frequency, severity (as graded by the NCI CTCAE v4.02), timing and relationship of study therapy of adverse events and laboratory abnormalities. Quantitative variables will be summarized in descriptive terms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life (QoL)</measure>
    <time_frame>1years</time_frame>
    <description>Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of predictive markers of treatment</measure>
    <time_frame>1years</time_frame>
    <description>To explore KRAS and HER family mutation status in tissue at the end of treatment;&#xD;
To explore the pre- and post-treatment levels of shed proteins/receptors related to HER signaling (possibly to include EGFR and HER-2 receptor extracellular domain (ECD) and E-cadherin);</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">49</enrollment>
  <condition>HNSCC</condition>
  <arm_group>
    <arm_group_label>HM781-36B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HM781-36B</intervention_name>
    <arm_group_label>HM781-36B</arm_group_label>
    <other_name>45 mg p.o. daily and continuously (28-day treatment as one treatment cycle)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed squamous cell carcinoma of head and neck&#xD;
&#xD;
          2. Age ≥ 20 years&#xD;
&#xD;
          3. ECOG PS 0-1&#xD;
&#xD;
               -  Documented progressive disease after platinum-based (either cisplatin or&#xD;
                  carboplatin) concurrent chemoradiation including induction chemotherapy for&#xD;
                  curative aim or&#xD;
&#xD;
               -  Documented progressive disease after platinum-based (either cisplatin or&#xD;
                  carboplatin) chemotherapy for palliative aim or&#xD;
&#xD;
               -  Ineligible to platinum-based (either cisplatin or carboplatin) chemotherapy or&#xD;
                  chemoradiation due to decline in renal function and patient's intolerance&#xD;
&#xD;
          4. At least one bidimensionally measurable disease as defined by RECIST ver 1.1&#xD;
&#xD;
          5. Adequate organ function for treatment&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1000cells/mm3&#xD;
&#xD;
               -  Platelets ≥ 100000 cells/mm3&#xD;
&#xD;
               -  Estimated creatinine clearance ≥ 50mL/min, or serum creatinine &lt; 1.5 x&#xD;
                  institution upper limit of normal&#xD;
&#xD;
               -  Bilirubin ≤ 1.5 x upper limit of normal(ULN)&#xD;
&#xD;
               -  AST(SGOT) ≤ 2.5 x ULN (5.0xULN if hepatic metastases)&#xD;
&#xD;
               -  ALT(SGPT) ≤ 2.5 x ULN (5.0xULN if hepatic metastases)&#xD;
&#xD;
          6. The patient has provided signed informed consent and is amenable to compliance with&#xD;
             protocol schedules and testing&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Nasopharyngeal carcinoma&#xD;
&#xD;
          2. Patients who are subjected to local treatment (surgery or radiation)&#xD;
&#xD;
          3. Previous treatment with small molecule EGFR tyrosine kinase inhibitors (Cetuximab is&#xD;
             permitted)&#xD;
&#xD;
          4. Three or more previous systemic cytotoxic chemotherapy&#xD;
&#xD;
          5. Any major operation or irradiation within 4 weeks of baseline disease assessment&#xD;
&#xD;
          6. Patients who have received prior systemic chemotherapy, immunotherapy or study drug&#xD;
             within 4 weeks&#xD;
&#xD;
          7. Any clinically significant gastrointestinal abnormalities which may impair intake or&#xD;
             absorption of the study drug&#xD;
&#xD;
          8. Patients with uncontrolled CNS metastatic involvement. However, patients with&#xD;
             metastatic CNS tumors may participate in this study if the patient is clinically&#xD;
             stable not receiving steroid therapy more than 1 week from prior therapy completion&#xD;
             (including radiation and/or surgery) to stating the study drug.&#xD;
&#xD;
          9. Patients with known interstitial lung disease (ILD) or presented ILD on screening&#xD;
             chest X-ray&#xD;
&#xD;
         10. Congenital long QT syndrome or screening corrected QT interval (QTc) &gt; 470msec&#xD;
&#xD;
         11. Patients with uncontrolled or significant cardiovascular disease (AMI within 12&#xD;
             months, Unstable angina within 6 months, NYHA Class III, IV Congestive heart failure&#xD;
             or left ventricular ejection fraction below local institutional lower limit of normal&#xD;
             or below 45%, Congenital long QT syndrome, Any significant ventricular arrhythmia, Any&#xD;
             uncontrolled second or third degree heart block, Uncontrolled hypertension)&#xD;
&#xD;
         12. Previous or concurrent malignancy except for basal or squamous cell skin cancer and/or&#xD;
             in situ carcinoma of the cervix, or other solid tumors treated curatively and without&#xD;
             evidence of recurrence for at least 3 years prior to study entry.&#xD;
&#xD;
         13. Pregnant or breast-feeding women&#xD;
&#xD;
         14. Other severe acute or chronic medical condition or laboratory abnormality that may&#xD;
             increase the risk associated with trial participation or investigational product&#xD;
             administration or may interfere with the interpretation of trial results and, in the&#xD;
             judgment of the investigator, would make the patient inappropriate for entry into this&#xD;
             trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Yonsei University</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Cho Byung Chul</last_name>
      <phone>82-10-5212-8867</phone>
      <phone_ext>84320</phone_ext>
      <email>cbc1971@yuhs.ac</email>
    </contact>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 15, 2014</study_first_posted>
  <last_update_submitted>March 14, 2019</last_update_submitted>
  <last_update_submitted_qc>March 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 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>Squamous Cell Carcinoma of Head and Neck</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/NCT02216916
org study id: 4-2013-0794
nct id: NCT02216916
lead sponsor: 
has dmc: Yes
Head and neck cancer is the sixth most common cancer and more than 650,000 new cases are
      diagnosed each year worldwide. About 60% of the HNSCC patients present with unresectable
      locally advanced disease at diagnosis and treated with multimodality approach. Despite such
      approach, majority (70%) of patients develop local or/and regional recurrences. Additional
      10% of patients present with distant metastasis at diagnosis. Most patients with recurrent or
      metastatic disease are treated with single agent chemotherapy, combination chemotherapy or
      targeted therapies.

      Despite its public health magnitude, HNSCC in Asian countries has received a limited
      attention for the drug development and cancer-related research. In fact, HNSCC ranked 7th
      among men and 10th among women by incidence in China, the largest producer and consumer of
      tobacco and alcohol. Recently, Chen et al. documented a 1:1:2 subset distribution for cancers
      of oral cavity, pharynx, and larynx in China, similar to the distribution reported in Korea
      but quite different from the general distribution of 5:2:3 in whites. Ethnic disparities in
      HNSCC also include its prognosis and this is partly explained by HPV-active disease ratio and
      genetic factors. Therefore, there is a strong need for an additional research in patients
      with HNSCC in Asia.

      Epidermal growth factor receptor (EGFR) is often over-expressed, and have been related to
      poor prognosis in patients with HNSCC. The association between EGFR-activated signaling
      pathways and tumor cell survival are well documented in many studies. EGFR targeting
      strategies showed clinical anti-tumor efficacy in patients with HNSCC, especially with
      monoclonal antibody, cetuximab. In the Extreme study, it was shown that the addition of
      cetuximab to platinum-5-FU significantly prolonged the median overall survival from 7.4
      months to 10.1 months compared to platinum-5FU alone in the first-line setting.

      HM781-36B is a irreversible pan-HER inhibitor. In preclinical studies, HM781-36B has much
      lower IC50 values than gefitinib in cell lines engineered to express EGFRvIII mutations and
      produces tumor growth inhibition in gefitinib-resistant xenografts. A phase I trial of
      HM781-36B in patients with advanced solid tumors showed clinically significant anti-tumor
      activity and a phase II trials of HM781-36B in patients with non-small cell lung cancer and
      advanced gastric cancer are currently ongoing.

      We suggest a phase II trial of HM781-36B in patients with recurrent or metastatic HNSCC who
      are resistant or ineligible/intolerant to platinum-based chemotherapy. The aim of current
      trial is to evaluate the antitumor efficacy and safety profile of HM781-36B and to identify
      biomarker to predict the tumor response to HM781-36B.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate
time frame: 28th day of 1st chemotherapy cycle
description: Objective Tumor Response will be performed according to the Response Evaluation in Solid Tumor Criteria 1.1 (RECIST 1.1)
measure: Best Overall Response
time frame: 1years
measure: Duration of response
time frame: 1years
measure: Progression-Free Survival
time frame: 1years
measure: Overall Survival
time frame: 1years
measure: Toxicity profile
time frame: 1years
description: Overall safety profile and toleration of HM781-36B will be characterized by type, frequency, severity (as graded by the NCI CTCAE v4.02), timing and relationship of study therapy of adverse events and laboratory abnormalities. Quantitative variables will be summarized in descriptive terms.
measure: Quality of Life (QoL)
time frame: 1years
description: Questionnaire
measure: Identification of predictive markers of treatment
time frame: 1years
description: To explore KRAS and HER family mutation status in tissue at the end of treatment;
To explore the pre- and post-treatment levels of shed proteins/receptors related to HER signaling (possibly to include EGFR and HER-2 receptor extracellular domain (ECD) and E-cadherin);
arm group label: HM781-36B
arm group type: Experimental
intervention type: Drug
intervention name: HM781-36B
arm group label: HM781-36B
other name: 45 mg p.o. daily and continuously (28-day treatment as one treatment cycle)
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Squamous Cell Carcinoma of Head and Neck