<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/NCT03792958</url>
  </required_header>
  <id_info>
    <org_study_id>CM082-CA-I-105</org_study_id>
    <nct_id>NCT03792958</nct_id>
  </id_info>
  <brief_title>Study of Challenge Meditech 082 (CM082) Tablets in Patients With Advanced Malignant Solid Tumors</brief_title>
  <official_title>Phase I Study of CM082 Tablets in the Treatment of Advanced Malignant Solid Tumors: Safety, Tolerance and Pharmacokinetics</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AnewPharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Shanghai East Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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 a Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and&#xD;
      Preliminary Efficacy of Oral Dosing of CM082 tablets in Chinese Patients With Advanced&#xD;
      Malignant Solid Tumors&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center、open-label and non-controlled Phase 1 study which will be conducted&#xD;
      in two parts: part A is the dose-escalation phase; part B is dose-expansion phase. The&#xD;
      dose-escalation phase is guided by pharmacokinetics (PK) and safety, according to the&#xD;
      standard 3+3 dose-escalation schema. CM082 tablets are taken orally with a starting dose of&#xD;
      200 mg and a subsequent dose of 400, 600 and 800 mg. The way of administration is as follows:&#xD;
      QD or BID. The primary objective of this study is to determine the maximum tolerable dose&#xD;
      (MTD)、characteristics of dose-limited toxicity (DLT) and pharmacokinetics (PK). Secondary&#xD;
      objectives include safety、tolerability and preliminary efficacy&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 26, 2019</start_date>
  <completion_date type="Anticipated">June 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</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>Sequential Assignment</intervention_model>
    <intervention_model_description>The initial dose is set at 200 mg, followed by 400 mg, 600 mg and 800 mg for dose increment.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerable dose (MTD) or dose to absorb saturation</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose-Limiting Toxicity</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>Characteristics of dose-limiting toxicity (DLT), evaluation criteria: National Cancer Institute (NCI) CTC classification (version 4.03)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>Peak concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>Area under the time curve of blood concentration from 0 h to the last time of blood collection</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>0 to Infinite Area under Blood Drug Concentration Curve</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>Peak time</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>Apparent terminal elimination half-life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic parameters</measure>
    <time_frame>From the first dose to the 28th day of administration</time_frame>
    <description>Terminal elimination rate constant</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>36 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Advanced Malignant Solid Tumors</condition>
  <arm_group>
    <arm_group_label>CM082</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CM082 tablet</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CM082</intervention_name>
    <description>CM082 tablets taken orally 200、400、600 and 800 mg (QD or BID)</description>
    <arm_group_label>CM082</arm_group_label>
    <other_name>X-82</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age:≥18 years.&#xD;
&#xD;
          -  BMI generally ranges from 18-28 (BMI=Weight (Kg)/Height (m)2)&#xD;
&#xD;
          -  Patients with advanced malignant solid tumors confirmed by histological or cytological&#xD;
             examination.&#xD;
&#xD;
          -  According to Recist1.1 criteria, patients have measurable or assessable tumors, and&#xD;
             patients with advanced malignant solid tumors who have failed to respond to previous&#xD;
             standard treatment regimens, are unable to tolerate previous treatment regimens or&#xD;
             lack effective treatment regimens.&#xD;
&#xD;
          -  Organ function level must meet the following requirements (7 days before treatment):&#xD;
&#xD;
               -  Bone marrow: absolute neutrophil count (ANC)≥1.5^109/L, platelet (PLT)≥100^109/L,&#xD;
                  hemoglobin (HB)≥9g/dL (no blood transfusion or component blood received within 14&#xD;
                  days before detection).&#xD;
&#xD;
               -  Liver: Serum bilirubin (TBIL) ≤1.5 * upper limit of normal (ULN) , aspartate&#xD;
                  aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 * ULN (If the&#xD;
                  patient's liver metastases, AST and ALT are allowed to be ≤ 5 * ULN) ).&#xD;
&#xD;
               -  Serum creatinine≤1.5 * ULN and endogenous creatinine clearance rate≥50mL/min.&#xD;
                  According to Cockcroft-Gault formula, Please refer to attachment 7 for details.&#xD;
&#xD;
               -  International normalized ratio (INR) and activated partial thromboplastin time&#xD;
                  (APTT)≤1.5 * ULN (This provision applies only to patients who do not receive&#xD;
                  anticoagulant treatment; for patients receiving anticoagulant treatment,&#xD;
                  anticoagulants should be used within the treatment requirements).&#xD;
&#xD;
               -  Urine protein (UP)≤1+. If UP&gt;1+, 24-hour UP should be collected for&#xD;
                  determination, and the total amount of UP should be ≤1g.&#xD;
&#xD;
               -  FT3、FT4 and thyroid-stimulating hormone (TSH) are normal or abnormal without&#xD;
                  clinical significance（Except for advanced thyroid cancer）.&#xD;
&#xD;
          -  No immunodeficiency.&#xD;
&#xD;
          -  The damage causes by other treatments is restored to 1 grade (CTCAE version 4.03),&#xD;
             except for hair loss and pigmentation; If the nutritional status is stable, the&#xD;
             long-term toxicity that cannot be recovered is allowed to exist by the&#xD;
             investigator'judgement.&#xD;
&#xD;
          -  Expected survival time≥ 3 months.&#xD;
&#xD;
          -  Eastern Cooperative Group (ECOG) Performance Status score of ≤1.&#xD;
&#xD;
          -  The results of serum pregnancy test for women of childbearing age should be negative&#xD;
             within 7 days before treatment.&#xD;
&#xD;
          -  Men who are fertile or women who are likely to become pregnant must use highly&#xD;
             effective contraceptive methods (e.g., oral contraceptives, intrauterine&#xD;
             contraceptives, sex control or barrier contraceptives combined with spermicides )&#xD;
             throughout the trial and continue to use contraception for 12 months after the end of&#xD;
             treatment.&#xD;
&#xD;
          -  Patients can voluntarily sign written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -Within 4 weeks before the first use of the study drug, the patient received anti- tumor&#xD;
        drug therapy such as chemotherapy, targeted therapy, radiotherapy, biological therapy or&#xD;
        endocrine therapy, except for the following: Nitrous urea or mitomycin C were used within 6&#xD;
        weeks before the first use of the study drug; Oral fluorouracil and small molecular&#xD;
        targeted drugs were used within 2 weeks before the first use of the study drug or within 5&#xD;
        half-lives (whichever is the longer); Chinese medicine with anti-cancer indications was&#xD;
        used within 1 week before the first use of the study drug.&#xD;
&#xD;
          -  Surgical treatment (except biopsy) was performed within 4 weeks before the first use&#xD;
             of study drug.&#xD;
&#xD;
          -  Patients who have participated in or are participating in any other drug/therapy&#xD;
             clinical trial (including but not limited to the anti-tumor clinical trial) within 4&#xD;
             weeks before treatment, counting from the time of last administration of the last&#xD;
             clinical trial.&#xD;
&#xD;
          -  Patients who received hematopoietic stimulating factors (e.g., granulocyte colony&#xD;
             stimulating factor (G-CSF), erythropoietin, etc.) within one week before treatment.&#xD;
&#xD;
          -  Pleural or ascites with clinical symptoms and requiring symptomatic treatment.&#xD;
&#xD;
          -  Patients with active pulmonary disease, interstitial pneumonia or pulmonary fibrosis.&#xD;
&#xD;
          -  Having any uncontrollable clinical problems or associated risk factors, including but&#xD;
             not limited to:&#xD;
&#xD;
               -  Poorly controlled hypertension (blood pressure persistently greater than 150/90&#xD;
                  mmHg).&#xD;
&#xD;
               -  Left ventricular ejection fraction (LVEF)≤50%.&#xD;
&#xD;
               -  The QT interval of heart rate correction (QTc) &gt; 450 msec (males) or 460 msec&#xD;
                  (females) ( Bazett's correction (QTcB)=QT/(RR^0.5)).&#xD;
&#xD;
               -  Patients have a clinically significant history of arrhythmia or current evidence&#xD;
                  of arrhythmia, but control of atrial fibrillation for more than 30 days before&#xD;
                  administration does not affect inclusion.&#xD;
&#xD;
               -  Patients implanted with cardiac defibrillator.&#xD;
&#xD;
               -  Poorly controlled diabetes [(fasting blood glucose should not be greater than 8.9&#xD;
                  mmol/L after drug control) refer to CTCAE version 4.03-grade 1 of hyperglycemia].&#xD;
&#xD;
               -  Heart disease (Class III/IV congestive heart failure or cardiac block defined by&#xD;
                  the New York Heart Association).&#xD;
&#xD;
               -  Decompensated cirrhosis.&#xD;
&#xD;
               -  The following conditions occur within 6 months before treatment:&#xD;
&#xD;
                    -  Deep venous thrombosis or pulmonary embolism.&#xD;
&#xD;
                    -  Myocardial infarction.&#xD;
&#xD;
                    -  Severe or unstable arrhythmia or angina pectoris.&#xD;
&#xD;
                    -  Percutaneous Coronary Intervention, Acute Coronary Syndrome, Coronary Artery&#xD;
                       Bypass Transplantation.&#xD;
&#xD;
                    -  Cerebrovascular accident, transient ischemic attack or resting limping of&#xD;
                       lower limbs.&#xD;
&#xD;
          -  Patients have not yet fully recovered from previous operations.&#xD;
&#xD;
          -  Patients who have taken strong inhibitors and inducers of CYP3A hepatic metabolic&#xD;
             enzymes within 2 weeks before treatment.&#xD;
&#xD;
          -  Patients also take drugs that are at risk of prolonging QTc and/or Tdp.&#xD;
&#xD;
          -  Patients with a history of allergy to CM082 similar drugs (e.g., sunitinib, sorafenib,&#xD;
             pazopanib, etc.).&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  Women/men with fertility who refuse to use contraception during the trial.&#xD;
&#xD;
          -  Any uncontrollable clinical problem (such as serious mental, neurological,&#xD;
             cardiovascular, respiratory and other system diseases) or active infection that&#xD;
             significantly affects clinical trials.&#xD;
&#xD;
          -  The patient has clinical symptoms or uncontrolled central nervous system metastasis or&#xD;
             meningeal metastasis, which is judged by the investigator to be unsuitable for&#xD;
             admission;&#xD;
&#xD;
          -  Patients with active upper gastrointestinal ulcer or other diseases known to affect&#xD;
             drug absorption, distribution, metabolism or clearance.&#xD;
&#xD;
          -  Patients with obvious abnormal gastrointestinal function such as vomiting、 diarrhea,&#xD;
             etc..&#xD;
&#xD;
          -  Positive results of HIV or Treponema pallidum antibodies (Acceptance of Treponema&#xD;
             pallidum antibody titer test results in a Class III Grade I hospital including&#xD;
             research centers).&#xD;
&#xD;
          -  Patients with active hepatitis B or C：&#xD;
&#xD;
               -  HBsAg or HBcAb are positive, and hepatitis B virus (HBV) DNA is detected (the&#xD;
                  results are higher than the upper limit of the normal range of the research&#xD;
                  center).&#xD;
&#xD;
               -  Hepatitis C virus (HCV) antibody test results are positive, and HCV RNA is&#xD;
                  detected (the results are higher than the upper limit of the normal range of the&#xD;
                  research center).&#xD;
&#xD;
          -  Patients who have progressed after using a receptor tyrosine kinase inhibitor that&#xD;
             targets VEGFR.&#xD;
&#xD;
          -  Investigators consider that it is not appropriate for subjects to participate in this&#xD;
             study from the perspective of clinical treatment.&#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>Jin Li, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai East Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200120</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>January 2, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 4, 2019</study_first_posted>
  <last_update_submitted>November 10, 2022</last_update_submitted>
  <last_update_submitted_qc>November 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 14, 2022</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>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vorolanib</mesh_term>
  </intervention_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/NCT03792958
org study id: CM082-CA-I-105
nct id: NCT03792958
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and
      Preliminary Efficacy of Oral Dosing of CM082 tablets in Chinese Patients With Advanced
      Malignant Solid Tumors
This is a single-center、open-label and non-controlled Phase 1 study which will be conducted
      in two parts: part A is the dose-escalation phase; part B is dose-expansion phase. The
      dose-escalation phase is guided by pharmacokinetics (PK) and safety, according to the
      standard 3+3 dose-escalation schema. CM082 tablets are taken orally with a starting dose of
      200 mg and a subsequent dose of 400, 600 and 800 mg. The way of administration is as follows:
      QD or BID. The primary objective of this study is to determine the maximum tolerable dose
      (MTD)、characteristics of dose-limited toxicity (DLT) and pharmacokinetics (PK). Secondary
      objectives include safety、tolerability and preliminary efficacy
allocation: N/A
intervention model: Sequential Assignment
intervention model description: The initial dose is set at 200 mg, followed by 400 mg, 600 mg and 800 mg for dose increment.
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerable dose (MTD) or dose to absorb saturation
time frame: From the first dose to the 28th day of administration
measure: Dose-Limiting Toxicity
time frame: From the first dose to the 28th day of administration
description: Characteristics of dose-limiting toxicity (DLT), evaluation criteria: National Cancer Institute (NCI) CTC classification (version 4.03)
measure: Pharmacokinetic parameters
time frame: From the first dose to the 28th day of administration
description: Peak concentration
measure: Pharmacokinetic parameters
time frame: From the first dose to the 28th day of administration
description: Area under the time curve of blood concentration from 0 h to the last time of blood collection
measure: Pharmacokinetic parameters
time frame: From the first dose to the 28th day of administration
description: 0 to Infinite Area under Blood Drug Concentration Curve
measure: Pharmacokinetic parameters
time frame: From the first dose to the 28th day of administration
description: Peak time
measure: Pharmacokinetic parameters
time frame: From the first dose to the 28th day of administration
description: Apparent terminal elimination half-life
measure: Pharmacokinetic parameters
time frame: From the first dose to the 28th day of administration
description: Terminal elimination rate constant
measure: Objective response rate
time frame: 12 months
measure: Disease control rate
time frame: 12 months
measure: Progression-free survival
time frame: 12 months
measure: Overall survival
time frame: 36 months
arm group label: CM082
arm group type: Experimental
description: CM082 tablet
intervention type: Drug
intervention name: CM082
description: CM082 tablets taken orally 200、400、600 and 800 mg (QD or BID)
arm group label: CM082
other name: X-82
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jin Li, M.D
role: Principal Investigator
affiliation: Shanghai East Hospital
facility: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Vorolanib