<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/NCT04413214</url>
  </required_header>
  <id_info>
    <org_study_id>Clarion I</org_study_id>
    <nct_id>NCT04413214</nct_id>
  </id_info>
  <brief_title>Carrimycin in Patients With Locally Advanced, Recurrent, or Metastatic HNSCC (Non NPC): A Phase I Trial</brief_title>
  <official_title>Safety and Efficacy Evaluation of Carrimycin in Patients With Locally Advanced, Recurrent, or Metastatic Head and Neck Squamous Cell Carcinoma (Non NPC): A Phase I Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The trial is a study conducted to evaluate the safety, tolerability and PK characteristics of&#xD;
      Carrimycin tablet and measure its anti-tumor efficacy initially in the treatment of patients&#xD;
      with locally advanced, recurrent, or metastatic head and neck squamous cell carcinoma (non&#xD;
      NPC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a prospective open phase-I study to investigate the safety, tolerability and PK&#xD;
      characteristics of Carrimycin tablet in the treatment of patients with locally advanced,&#xD;
      recurrent, or metastatic head and neck squamous cell carcinoma (non NPC). The 3x3 dose&#xD;
      escalation design will be adopted, including 200mg, 400mg and 600mg of Carrimycin; and three&#xD;
      subjects at each dose level initially. If there is no DLT in the dose level of 200mg, the&#xD;
      dose level of 400mg will be followed; if there is one DLT in the dose level of 200mg, another&#xD;
      three patients will be added in the dose level of 200mg; if there is no DLT occurs in the&#xD;
      another three patients, the dose level of 400mg will also be followed; if there is one DLT in&#xD;
      the another three patients, the trial will be closed. The same condition to the dose level of&#xD;
      400mg and 600mg. If a patient fails to receive the full prescribed dose for reasons other&#xD;
      than DLT at the time of the first administration, the patient will be replaced. Carrimycin&#xD;
      treatment to the patients with DLT will be discontinued immediately and they will enter the&#xD;
      follow-up period and will not be replaced. The study consists of screening period, treatment&#xD;
      period and follow-up period. The treatment period continues until the patients develop&#xD;
      progressive disease, dies, lost to follow-up or withdraw informed consent.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 20, 2019</start_date>
  <completion_date type="Actual">December 30, 2022</completion_date>
  <primary_completion_date type="Actual">December 30, 2022</primary_completion_date>
  <phase>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>Incidence of treatment-emergent adverse events</measure>
    <time_frame>Two years</time_frame>
    <description>According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0, evaluate adverse events occurred during the whole study period.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose limiting toxicity</measure>
    <time_frame>Four weeks</time_frame>
    <description>According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0, observe the dose limiting toxicity (DLT).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate to Carrimycin</measure>
    <time_frame>Four weeks</time_frame>
    <description>Including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>Two years</time_frame>
    <description>The period between the time a patient with a cancer disease begins to receive treatment and observe the disease progression or die for any reason</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Oral Squamous Cell Carcinoma</condition>
  <condition>Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Test Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The 3x3 dose escalation design will be adopted, including 200mg, 400mg and 600mg of Carrimycin; and three subjects at each dose level initially. If there is no DLT in the dose level of 200mg, the dose level of 400mg will be followed; if there is one DLT in the dose level of 200mg, another three patients will be added in the dose level of 200mg; if there is no DLT occurs in the another three patients, the dose level of 400mg will also be followed; if there is one DLT in the another three patients, the trial will be closed. The same condition to the dose level of 400mg and 600mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carrimycin</intervention_name>
    <description>The study involves three dose groups: 200mg, 400mg and 600mg. Three patients are planned for each dose group. Starting from the low dose group, the treatment to three patients in the 200mg dose group: 200mg of Carrimycin after meals every morning (po) for three weeks, and then discontinue for one week, the tolerance and efficacy evaluation will be performed after the 4 weeks. DLT will be recorded during the 4 weeks.</description>
    <arm_group_label>Test Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Locally advanced, recurrent, or metastatic head and neck squamous cell carcinoma (non&#xD;
             NPC) confirmed by histopathological or cytological diagnosis&#xD;
&#xD;
          -  Expected life expectancy is no less than 6 months;&#xD;
&#xD;
          -  ECOG PS is 0, 1 or 2;&#xD;
&#xD;
          -  Subjects should be enrolled at least 4 weeks after the lastest treatment of surgery,&#xD;
             radiotherapy, chemotherapy, or biotherapy, etc.&#xD;
&#xD;
          -  The laboratory inspection indexes should meet the following requirements:&#xD;
             Leukocyte&gt;3×109/L, Neutrophils&gt;1.5×109/L, Platelet count&gt;75×109/L，Hemoglobin&gt;80g/L,&#xD;
             Serum total bilirubin&lt;1.5ULN, ALT or AST&lt;2.5ULN, Creatinine&lt;2.0ULN, BUN&lt;2.0ULN,&#xD;
             Maximum extension of APTT normal is within 10s, Maximum extension of PT normal is&#xD;
             within 3s.&#xD;
&#xD;
          -  Women of reproductive age (18-45 years) must have a negative urine pregnancy test and&#xD;
             agree to receive effective contraception. Male subjects must voluntarily receive&#xD;
             appropriate contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  There is still any undiminished CTCAE grade 2 or higher toxicity from previous&#xD;
             anti-cancer treatments;&#xD;
&#xD;
          -  There are significant cardiovascular abnormalities (e.g. myocardial infarction,&#xD;
             upper-cavity venous syndrome, heart disease of grade 2 or higher diagnosed according&#xD;
             to the New York Heart Association (NYHA) classification criteria 3 months prior to&#xD;
             enrollment);&#xD;
&#xD;
          -  There is active severe clinical infection (&gt;NCI-CTCAE V5.0 Level 2)&#xD;
&#xD;
          -  Urine routine shows albuminuria ≥ ++, but if albuminuria at baseline ≥ ++, patients&#xD;
             with albuminuria /24h&lt;1g measured quantitatively based on 24-hour urine collection can&#xD;
             be enrolled;&#xD;
&#xD;
          -  Allergic to macrolides;&#xD;
&#xD;
          -  Uncontrolled hypertension (systolic &gt; 150 mmHg and / or diastolic &gt;100mmHg) or&#xD;
             clinically significant (e.g. active) cardiovascular diseases - such as stroke (≤ 6&#xD;
             months before randomization), myocardial infarction (≤ 6 months before randomization),&#xD;
             unstable angina pectoris, congestive heart failure of New York Heart Association&#xD;
             (NYHA) functional class III or above, or serious arrhythmia that cannot be controlled&#xD;
             with drugs or has potential impact on trial treatment.&#xD;
&#xD;
          -  Known to have acute or chronic active HBV or HCV infection and need antiviral&#xD;
             treatment with non nucleoside drugs;&#xD;
&#xD;
          -  Women pregnant or lactation;&#xD;
&#xD;
          -  Having participated in other clinical studies and received any other investigational&#xD;
             drug for treatment within 30 days before enrollment;&#xD;
&#xD;
          -  Having taken macrolide antibiotics (azithromycin, erythromycin, roxithromycin,&#xD;
             clarithromycin, dirithromycin, spiramycin, acetylspiramycin, midecamycin, rokitamycin,&#xD;
             meleumycin, josamycin, leucomycin, miocamycin) within 3 days before enrollment;&#xD;
&#xD;
          -  Other cases considered inappropriate by the investigator to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lai-ping Zhong, PhD/MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>April 4, 2023</last_update_submitted>
  <last_update_submitted_qc>April 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Lai-ping Zhong</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </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>
  <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/NCT04413214
org study id: Clarion I
nct id: NCT04413214
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The trial is a study conducted to evaluate the safety, tolerability and PK characteristics of
      Carrimycin tablet and measure its anti-tumor efficacy initially in the treatment of patients
      with locally advanced, recurrent, or metastatic head and neck squamous cell carcinoma (non
      NPC).
This study is a prospective open phase-I study to investigate the safety, tolerability and PK
      characteristics of Carrimycin tablet in the treatment of patients with locally advanced,
      recurrent, or metastatic head and neck squamous cell carcinoma (non NPC). The 3x3 dose
      escalation design will be adopted, including 200mg, 400mg and 600mg of Carrimycin; and three
      subjects at each dose level initially. If there is no DLT in the dose level of 200mg, the
      dose level of 400mg will be followed; if there is one DLT in the dose level of 200mg, another
      three patients will be added in the dose level of 200mg; if there is no DLT occurs in the
      another three patients, the dose level of 400mg will also be followed; if there is one DLT in
      the another three patients, the trial will be closed. The same condition to the dose level of
      400mg and 600mg. If a patient fails to receive the full prescribed dose for reasons other
      than DLT at the time of the first administration, the patient will be replaced. Carrimycin
      treatment to the patients with DLT will be discontinued immediately and they will enter the
      follow-up period and will not be replaced. The study consists of screening period, treatment
      period and follow-up period. The treatment period continues until the patients develop
      progressive disease, dies, lost to follow-up or withdraw informed consent.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of treatment-emergent adverse events
time frame: Two years
description: According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0, evaluate adverse events occurred during the whole study period.
measure: Dose limiting toxicity
time frame: Four weeks
description: According to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 5.0, observe the dose limiting toxicity (DLT).
measure: Objective response rate to Carrimycin
time frame: Four weeks
description: Including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD)
measure: Progression-free survival
time frame: Two years
description: The period between the time a patient with a cancer disease begins to receive treatment and observe the disease progression or die for any reason
arm group label: Test Group
arm group type: Experimental
description: The 3x3 dose escalation design will be adopted, including 200mg, 400mg and 600mg of Carrimycin; and three subjects at each dose level initially. If there is no DLT in the dose level of 200mg, the dose level of 400mg will be followed; if there is one DLT in the dose level of 200mg, another three patients will be added in the dose level of 200mg; if there is no DLT occurs in the another three patients, the dose level of 400mg will also be followed; if there is one DLT in the another three patients, the trial will be closed. The same condition to the dose level of 400mg and 600mg.
intervention type: Drug
intervention name: Carrimycin
description: The study involves three dose groups: 200mg, 400mg and 600mg. Three patients are planned for each dose group. Starting from the low dose group, the treatment to three patients in the 200mg dose group: 200mg of Carrimycin after meals every morning (po) for three weeks, and then discontinue for one week, the tolerance and efficacy evaluation will be performed after the 4 weeks. DLT will be recorded during the 4 weeks.
arm group label: Test Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Lai-ping Zhong, PhD/MD
role: Principal Investigator
affiliation: Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Jiao Tong University School of Medicine
investigator full name: Lai-ping Zhong
investigator title: Principal Investigator
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
sharing ipd: No