<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/NCT03286244</url>
  </required_header>
  <id_info>
    <org_study_id>CM082-CA-I-104</org_study_id>
    <nct_id>NCT03286244</nct_id>
  </id_info>
  <brief_title>Second-line CM082 Combined With Paclitaxel For Patients With Advanced Gastric Cancer</brief_title>
  <official_title>Safety and Preliminary Efficacy of CM082 in Combination With Paclitaxel for Treating Advanced Gastric Cancer Who Progressed on Standard First-line Treatment: a Phase 1, Dose-escalation Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AnewPharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AnewPharma</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>
      This is an open-label, Phase 1b study which will be conducted in two parts: part A is the&#xD;
      dose escalation study while part B is dose expansion study. The purpose of the dose&#xD;
      escalation part is to identify the maximum tolerated dose (MTD) and/or recommended phase II&#xD;
      dose (RP2D) of CM082 combined with paclitaxel in patients with advanced gastric cancer who&#xD;
      did not respond to first-line standard chemotherapy. In the subsequent dose expansion part,&#xD;
      additional subjects will be enrolled to further explore the safety and preliminary clinical&#xD;
      activity of CM082 and paclitaxel.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In dose escalation part, 9-18 patients with advanced gastric cancer will be enrolled.&#xD;
      Patients meeting enrollment eligibility will receive 28-day cycles of CM082 100-200 mg qd&#xD;
      combined with paclitaxel 80 mg/m2. Safety information will be collected in cycle 1 to&#xD;
      determine MTD and/or RP2D of CM082 combined with paclitaxel in patients with advanced gastric&#xD;
      cancer.&#xD;
&#xD;
      Dose escalation study will use traditional 3+3 trial design to observe DLT and evaluate MTD.&#xD;
      If there are 2 or more cases of DLT in one dose group, the group lower than this dose group&#xD;
      by one level is MTD dose group. At least 6 subjects are required in MTD dose group for&#xD;
      confirmation. If MTD is not achieved at the end of dose escalation and there are 6 subjects&#xD;
      in the highest dose group, 200 mg qd will be determined as RP2D. Dose escalation and study in&#xD;
      the next dose group can be initiated only after the first treatment cycle (DLT window&#xD;
      observation period) is completed and safety and tolerability in subject is confirmed in this&#xD;
      dose group (0/3 or ≤1/6 subjects experience DLT).&#xD;
&#xD;
      Subjects in the original dose group will continue to receive the next cycle of treatment at&#xD;
      the original dose until it meets the following discontinued treatment criteria: 1) death, 2)&#xD;
      intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be&#xD;
      terminated for the subject's best interests, 5) the subject or legal representative requests&#xD;
      withdrawal, 6) loss to follow-up, 7) the investigator considers the subject has poor&#xD;
      compliance, 8) disease progression, 9) the investigator considers the toxicity effect will be&#xD;
      intensified if the study continues, 10) use other anti-tumor drugs.&#xD;
&#xD;
      In dose-expansion part, additional patients will be treated at the RP2D established in dose&#xD;
      escalation part until it meets the discontinued treatment criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 15, 2018</start_date>
  <completion_date type="Anticipated">August 2020</completion_date>
  <primary_completion_date type="Anticipated">August 2019</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>DLT and MTD</measure>
    <time_frame>4 weeks</time_frame>
    <description>DLTs were defined as grade 4 hematological toxicity; grade 3 or more severe nonhematologic toxicity including nausea/vomit, constipation , Hypertension , not controlled by adequate supportive treatment (with exceptions of alopecia); grade 3 febrile neutropenia. The MTD was defined as the highest dose at which no DLT was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of patients who suffer at least one adverse event</measure>
    <time_frame>From first dose to within 28 days after the last dose</time_frame>
    <description>Adverse event assessment and changes in safety assessments include laboratory parameters, vital signs, and ECOG score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>12 weeks</time_frame>
    <description>Defined as the rate of either a complete response or a partial response in evaluable patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>6 months</time_frame>
    <description>Defined as the time from randomisation to disease progression or death</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">21</enrollment>
  <condition>Advanced Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>CM082 plus paclitaxel</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In dose-escalation part, patients will be treated in dose levels at the following daily doses of CM082 and paclitaxel to establish the MTD and RP2D:&#xD;
CM082 100mg qd + paclitaxel 80mg/m2/day; CM082 150mg qd + paclitaxel 80mg/m2/day; CM082 200mg qd + paclitaxel 80mg/m2/day; In dose-expansion part, patients will be treated at the RP2D established in dose escalation part.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CM082 plus paclitaxel</intervention_name>
    <description>CM082 treatment: A treatment cycle is defined as 28 days. Oral CM082 tablets was given once daily for 3 weeks followed by 1-week break with escalating dose (100 mg, 150 mg and 200mg).&#xD;
Drug: Paclitaxel Paclitaxel 80 mg/m2 will be administrated by intravenous injection on days 1, 8, 15 of a 28-day cycle for no more than 6 cycles.</description>
    <arm_group_label>CM082 plus paclitaxel</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Fully understand the study and sign the informed consent voluntarily;&#xD;
&#xD;
          -  Patients with local advanced and/or metastatic gastric adenocarcinoma and/or&#xD;
             adenocarcinoma of gastroesophageal junction confirmed by histology and/or cytology;&#xD;
&#xD;
          -  Progressed on previous first-line standard chemotherapy;&#xD;
&#xD;
          -  Male or female with an age of 18-70 years(inclusive);&#xD;
&#xD;
          -  Body weight ≥40 kg (inclusive);&#xD;
&#xD;
          -  At least one measurable lesion (according to RECIST1.1);&#xD;
&#xD;
          -  Performance status score (ECOG score) 0-1;&#xD;
&#xD;
          -  Expected survival &gt;12 weeks;&#xD;
&#xD;
          -  Adequate bonemarrow, liver, renal and cardiac function, based on blood tests,&#xD;
             electrocardiograms, and cardiac echocardiograms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participating in another drug clinical trial in the past 4 weeks; history of systemic&#xD;
             anti-tumor treatment within 4 weeks prior to administration of the study drug; history&#xD;
             of any major surgery within 4 weeks prior to enrollment to the study;&#xD;
&#xD;
          -  Who have not recovered from toxicity caused by previous anti-cancer treatment&#xD;
             (CTCAE&gt;grade 1), or not completely recovered from previous surgery;&#xD;
&#xD;
          -  Having received previous chemotherapy regimens with taxanes;&#xD;
&#xD;
          -  Take medications that may extend QTc and/or Tdp;&#xD;
&#xD;
          -  Active brain metastasis or meningeal metastasis;&#xD;
&#xD;
          -  Uncontrolled hypertension (BP&gt;150/90 on medications);&#xD;
&#xD;
          -  Other malignancies within the last 5 years, except for adequately treated cervix&#xD;
             carcinoma in situ or basal or squamous-cell or basal cell carcinoma;&#xD;
&#xD;
          -  QT interval &gt; 450 ms;&#xD;
&#xD;
          -  Uncontrolled clinical active infection, e.g. acute pneumonia, active hepatitis B or&#xD;
             hepatitis C; HIV positive; syphilitic spiral antibody positive;&#xD;
&#xD;
          -  Dysphagia, intractable vomiting or known drug malabsorption;&#xD;
&#xD;
          -  Drug or alcohol abuser.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aiping Zhou, MD</last_name>
    <role>Study Chair</role>
    <affiliation>National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aiping Zhou, MD</last_name>
    <phone>8610-87788800</phone>
    <email>zhouap1825@126.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College</name>
      <address>
        <city>Beijing</city>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Aiping Zhou</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>February 2019</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 18, 2017</study_first_posted>
  <last_update_submitted>February 19, 2019</last_update_submitted>
  <last_update_submitted_qc>February 19, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 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>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03286244
org study id: CM082-CA-I-104
nct id: NCT03286244
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is an open-label, Phase 1b study which will be conducted in two parts: part A is the
      dose escalation study while part B is dose expansion study. The purpose of the dose
      escalation part is to identify the maximum tolerated dose (MTD) and/or recommended phase II
      dose (RP2D) of CM082 combined with paclitaxel in patients with advanced gastric cancer who
      did not respond to first-line standard chemotherapy. In the subsequent dose expansion part,
      additional subjects will be enrolled to further explore the safety and preliminary clinical
      activity of CM082 and paclitaxel.
In dose escalation part, 9-18 patients with advanced gastric cancer will be enrolled.
      Patients meeting enrollment eligibility will receive 28-day cycles of CM082 100-200 mg qd
      combined with paclitaxel 80 mg/m2. Safety information will be collected in cycle 1 to
      determine MTD and/or RP2D of CM082 combined with paclitaxel in patients with advanced gastric
      cancer.

      Dose escalation study will use traditional 3+3 trial design to observe DLT and evaluate MTD.
      If there are 2 or more cases of DLT in one dose group, the group lower than this dose group
      by one level is MTD dose group. At least 6 subjects are required in MTD dose group for
      confirmation. If MTD is not achieved at the end of dose escalation and there are 6 subjects
      in the highest dose group, 200 mg qd will be determined as RP2D. Dose escalation and study in
      the next dose group can be initiated only after the first treatment cycle (DLT window
      observation period) is completed and safety and tolerability in subject is confirmed in this
      dose group (0/3 or ≤1/6 subjects experience DLT).

      Subjects in the original dose group will continue to receive the next cycle of treatment at
      the original dose until it meets the following discontinued treatment criteria: 1) death, 2)
      intolerable toxicity, 3) pregnancy, 4) the investigator considers the study should be
      terminated for the subject's best interests, 5) the subject or legal representative requests
      withdrawal, 6) loss to follow-up, 7) the investigator considers the subject has poor
      compliance, 8) disease progression, 9) the investigator considers the toxicity effect will be
      intensified if the study continues, 10) use other anti-tumor drugs.

      In dose-expansion part, additional patients will be treated at the RP2D established in dose
      escalation part until it meets the discontinued treatment criteria.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLT and MTD
time frame: 4 weeks
description: DLTs were defined as grade 4 hematological toxicity; grade 3 or more severe nonhematologic toxicity including nausea/vomit, constipation , Hypertension , not controlled by adequate supportive treatment (with exceptions of alopecia); grade 3 febrile neutropenia. The MTD was defined as the highest dose at which no DLT was experienced by the first 3 patients in that cohort, or the dose at which a DLT was experienced by no more than 1 of 6 patients evaluable for toxicity.
measure: Percentage of patients who suffer at least one adverse event
time frame: From first dose to within 28 days after the last dose
description: Adverse event assessment and changes in safety assessments include laboratory parameters, vital signs, and ECOG score
measure: Objective response rate
time frame: 12 weeks
description: Defined as the rate of either a complete response or a partial response in evaluable patients
measure: Progression-free survival
time frame: 6 months
description: Defined as the time from randomisation to disease progression or death
arm group label: CM082 plus paclitaxel
arm group type: Experimental
description: In dose-escalation part, patients will be treated in dose levels at the following daily doses of CM082 and paclitaxel to establish the MTD and RP2D:
CM082 100mg qd + paclitaxel 80mg/m2/day; CM082 150mg qd + paclitaxel 80mg/m2/day; CM082 200mg qd + paclitaxel 80mg/m2/day; In dose-expansion part, patients will be treated at the RP2D established in dose escalation part.
intervention type: Drug
intervention name: CM082 plus paclitaxel
description: CM082 treatment: A treatment cycle is defined as 28 days. Oral CM082 tablets was given once daily for 3 weeks followed by 1-week break with escalating dose (100 mg, 150 mg and 200mg).
Drug: Paclitaxel Paclitaxel 80 mg/m2 will be administrated by intravenous injection on days 1, 8, 15 of a 28-day cycle for no more than 6 cycles.
arm group label: CM082 plus paclitaxel
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Aiping Zhou, MD
role: Study Chair
affiliation: National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
last name: Aiping Zhou, MD
phone: 8610-87788800
email: zhouap1825@126.com
facility: 
status: Recruiting
investigator: 
country: China
responsible party type: Sponsor
mesh term: Stomach Neoplasms
mesh term: Paclitaxel
sharing ipd: Undecided