<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/NCT03017807</url>
  </required_header>
  <id_info>
    <org_study_id>KL140-I-01-CTP</org_study_id>
    <nct_id>NCT03017807</nct_id>
  </id_info>
  <brief_title>Safety and Pharmacokinetics of Recombinant Anti-EGFr Antibody in Patients With Metastatic Colorectal Cancer</brief_title>
  <official_title>A PhaseⅠ,Open-label, Single-center Study to Evaluate Safety and Pharmacokinetics of Recombinant Anti-Epidermal Growth Factor Receptor (EGFr) Antibody in Patients With Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sichuan Kelun Pharmaceutical Co., Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>307 Hospital of PLA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sichuan Kelun Pharmaceutical Research Institute Co., Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A single-central,open-label,safety,pharmacokinetics,phase I study. Biological:Recombinant&#xD;
      Anti-EGFr Antibody Two dose levels: Low-dose level patients received initial dose 100 mg/m2&#xD;
      and 4 weeks later 250 mg/m2 weekly maintenance to the disease progression or unacceptable&#xD;
      toxicity or death or withdraw informed consent.High-dose level patients received cetuximab&#xD;
      initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance&#xD;
      to the disease progression or unacceptable toxicity or death or withdraw informed consent.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Two dose levels were tested: Recombinant Anti-EGFr Antibody Low-dose level patients received&#xD;
      initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance to the disease&#xD;
      progression or unacceptable toxicity or death or withdraw informed consent.High-dose level&#xD;
      patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and&#xD;
      250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or&#xD;
      withdraw informed consent. Dose limiting toxicity (DLT) was defined as: grade 4 or 3-time&#xD;
      grade 3 cutaneous toxicity,successive 3-time infusion suspension due to grade 3 cutaneous&#xD;
      toxicity,any other ≥grade 3 adverse reaction or acute pneumonia, interstitial pneumonia, and&#xD;
      other lung diseases.&#xD;
&#xD;
      Cohorts of 3 patients receive single dose of low-dose group of Recombinant Anti-EGFr&#xD;
      Antibody. If the ratio of the dose limiting toxicity (DLT) after a single dose is not more&#xD;
      than a third, then high-dose group can be treated.After high-dose(initial dose 400 mg/m2,&#xD;
      iv., 2 h),safety will be observed and blood sampling will be taken for a single dose&#xD;
      pharmacokinetic analysis.After 4-week continuous administration (loading dose 400 mg/m2, iv.,&#xD;
      2 h; maintenance dose 250 mg/m2, iv, 1 h, q1w) until disease progression, unacceptable&#xD;
      toxicity reaction, death or revocation of informed consent.As the blood concentration reach&#xD;
      steady state, blood sampling will be collected for steady-state pharmacokinetic analysis, for&#xD;
      1 week.After completion of the steady-state pharmacokinetics,patients can receive&#xD;
      chemotherapy,and safety (including immunogenicity) and curative effect will be observed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">October 2017</completion_date>
  <primary_completion_date type="Anticipated">June 2017</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>Number of patients with dose limiting toxicity.</measure>
    <time_frame>4 weeks after the single dose</time_frame>
    <description>Dose limiting toxicity (DLT) was defined as: grade 4 or 3-time grade 3 cutaneous toxicity,successive 3-time infusion suspension due to grade 3 cutaneous toxicity,any other ≥grade 3 adverse reaction or acute pneumonia, interstitial pneumonia, and other lung diseases.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in serum antibody and its neutralizing ability</measure>
    <time_frame>Prior to the single dose on day 1 and on the 1st day of 1、2、4、6、9 week after the first administration until 1 month after the last administration.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of anti-EGFR antibody after single dose and under the stable blood concentration.</measure>
    <time_frame>4 weeks after the single dose and 1 week under the stable blood concentration after weekly administration.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Recombinant Anti-EGFr Antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low-dose level patients received cetuximab initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Recombinant Anti-EGFr Antibody</intervention_name>
    <description>Low-dose level patients received cetuximab initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.</description>
    <arm_group_label>Recombinant Anti-EGFr Antibody</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages eligible for study between 18 Years and 75 Years.&#xD;
&#xD;
          2. Confirmed histological diagnosis of colorectal cancer.&#xD;
&#xD;
          3. Subjects with advanced/metastatic Colorectal Cancer(CRC) who have failed to the&#xD;
             irinotecan- ,oxaliplatin- and fluoropyrimidine-based regimens or been intolerant to&#xD;
             irinotecan or rejected the chemotherapy.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) of 0 or 1.&#xD;
&#xD;
          5. Subjects must have a life expectancy of at least 12 weeks.&#xD;
&#xD;
          6. Patients with at least one evaluable lesion (evaluable disease) by the RECIST&#xD;
             criteria.&#xD;
&#xD;
          7. Adequate renal function (creatinine ≤ 1.5 x UNL), liver function (total bilirubin ≤&#xD;
             1.5 x UNL, alanine aminotransferase(ALT)&lt; 2.5 x UNL, aspartate aminotransferase(AST) &lt;&#xD;
             2.5 x UNL or ≤ 5 x UNL if hepatic metastasis) and leucocytes ≥ 3×10^9, absolute&#xD;
             neutrophil count ≥ 1.5×10^9/L, platelets &gt; 80×10^9/L, haemoglobin ≥ 9 g/dl.&#xD;
             Electrolyte: in the normal range, or abnormal but no clinical significance (judged by&#xD;
             the researchers), allow to give supplements to correct the electrolyte.&#xD;
&#xD;
          8. Both women of child-bearing potential and sexually active men must agree to use&#xD;
             adequate contraception prior to study entry and for the duration of study&#xD;
             participation and for 90 days after the conclusion of study therapy.&#xD;
&#xD;
          9. Patients who have capable to understand the procedure and methods of the study,are&#xD;
             willing to strictly follow the protocol and sign the the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous therapy with anti-EGFR drugs.&#xD;
&#xD;
          2. Patients who are receiving other accompanying antineoplastic therapy (including&#xD;
             antitumor treatment with traditional Chinese medicine), long-term systemic immune&#xD;
             therapy, or hormone therapy except for physiological replacement therapy (for example,&#xD;
             people with thyroid hypofunction receive the thyroid hormone).&#xD;
&#xD;
          3. Radiotherapy or surgery (except always diagnostic biopsy).&#xD;
&#xD;
          4. Patients with known cerebral metastasis or leptomeningeal metastasis.&#xD;
&#xD;
          5. Any other malignant tumour in the last five years, except for suitably treated in situ&#xD;
             cervical carcinoma or basal cell carcinoma.&#xD;
&#xD;
          6. Clinically significant cardiovascular disease, such as heart failure (NYHA Ⅲ-Ⅳ),&#xD;
             uncontrolled coronary heart disease, cardiomyopathy, cardiac arrhythmias, hypertension&#xD;
             (&gt; 140/90 mmHg), myocardial infarction in the last half year, echocardiogram showed&#xD;
             ejection fraction &lt; 50%.&#xD;
&#xD;
          7. Patients with any symptom of acute or subacute bowel obstruction and/or inflammatory&#xD;
             bowel disease.&#xD;
&#xD;
          8. Patients with known active and severe infections(&gt; grade 2, National Cancer Institute&#xD;
             Common Toxicity Criteria(NCI-CTC) adverse effect(AE) V. 4.03), including active&#xD;
             tuberculosis(TB).&#xD;
&#xD;
          9. HIV infection or active hepatitis B or hepatitis C.&#xD;
&#xD;
         10. Uncontrolled diabetes (&gt; grade 2, NCI-CTC AE V. 4.03), severe lung disease (acute lung&#xD;
             disease, pulmonary fibrosis that affect the lung function, and interstitial lung&#xD;
             disease), liver failure.&#xD;
&#xD;
         11. Patients with blood coagulation dysfunction as following situation: prothrombin time&#xD;
             (PT) ≥ 1.5 x UNL, thrombin time (TT) ≥ 1.5 x UNL, the part activated clotting time&#xD;
             (APTT) ≥ 1.5 x UNL.&#xD;
&#xD;
         12. Patients who have blood transfusion, or use the g-csf cytokines etc in the last 10&#xD;
             days.&#xD;
&#xD;
         13. Known hypersensitivity to any component of pretreated product.&#xD;
&#xD;
         14. Pregnancy or breastfeeding.&#xD;
&#xD;
         15. Patients with known drug and/or alcohol abuse.&#xD;
&#xD;
         16. Patients with a clear history of neurological or psychiatric disorders, including&#xD;
             epilepsy or dementia.&#xD;
&#xD;
         17. Patient participation in another clinical trial or receive other research drugs during&#xD;
             the previous 4 weeks.&#xD;
&#xD;
         18. Patients with a medical or mental abnormalities unable to give informed consent.&#xD;
&#xD;
         19. Lack of legal behavior ability or limited legal behavior ability.&#xD;
&#xD;
         20. Other factors that may affect the efficacy or safety evaluation of this study assessed&#xD;
             by researchers.&#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_contact>
    <last_name>Zhou Jianglin</last_name>
    <phone>86-028-67252675</phone>
    <email>zhoujl@kelun.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Sichuan Kelun Pharmaceutical Co., Ltd.</name>
      <address>
        <city>Chengdu</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhou Jianglin</last_name>
      <phone>86-028-67252675</phone>
      <email>zhoujl@kelun.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 29, 2016</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <last_update_submitted>January 9, 2017</last_update_submitted>
  <last_update_submitted_qc>January 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 11, 2017</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>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</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/NCT03017807
org study id: KL140-I-01-CTP
nct id: NCT03017807
lead sponsor: 
collaborator: 
has dmc: No
A single-central,open-label,safety,pharmacokinetics,phase I study. Biological:Recombinant
      Anti-EGFr Antibody Two dose levels: Low-dose level patients received initial dose 100 mg/m2
      and 4 weeks later 250 mg/m2 weekly maintenance to the disease progression or unacceptable
      toxicity or death or withdraw informed consent.High-dose level patients received cetuximab
      initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance
      to the disease progression or unacceptable toxicity or death or withdraw informed consent.
Two dose levels were tested: Recombinant Anti-EGFr Antibody Low-dose level patients received
      initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance to the disease
      progression or unacceptable toxicity or death or withdraw informed consent.High-dose level
      patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and
      250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or
      withdraw informed consent. Dose limiting toxicity (DLT) was defined as: grade 4 or 3-time
      grade 3 cutaneous toxicity,successive 3-time infusion suspension due to grade 3 cutaneous
      toxicity,any other ≥grade 3 adverse reaction or acute pneumonia, interstitial pneumonia, and
      other lung diseases.

      Cohorts of 3 patients receive single dose of low-dose group of Recombinant Anti-EGFr
      Antibody. If the ratio of the dose limiting toxicity (DLT) after a single dose is not more
      than a third, then high-dose group can be treated.After high-dose(initial dose 400 mg/m2,
      iv., 2 h),safety will be observed and blood sampling will be taken for a single dose
      pharmacokinetic analysis.After 4-week continuous administration (loading dose 400 mg/m2, iv.,
      2 h; maintenance dose 250 mg/m2, iv, 1 h, q1w) until disease progression, unacceptable
      toxicity reaction, death or revocation of informed consent.As the blood concentration reach
      steady state, blood sampling will be collected for steady-state pharmacokinetic analysis, for
      1 week.After completion of the steady-state pharmacokinetics,patients can receive
      chemotherapy,and safety (including immunogenicity) and curative effect will be observed.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients with dose limiting toxicity.
time frame: 4 weeks after the single dose
description: Dose limiting toxicity (DLT) was defined as: grade 4 or 3-time grade 3 cutaneous toxicity,successive 3-time infusion suspension due to grade 3 cutaneous toxicity,any other ≥grade 3 adverse reaction or acute pneumonia, interstitial pneumonia, and other lung diseases.
measure: Change from baseline in serum antibody and its neutralizing ability
time frame: Prior to the single dose on day 1 and on the 1st day of 1、2、4、6、9 week after the first administration until 1 month after the last administration.
measure: Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of anti-EGFR antibody after single dose and under the stable blood concentration.
time frame: 4 weeks after the single dose and 1 week under the stable blood concentration after weekly administration.
arm group label: Recombinant Anti-EGFr Antibody
arm group type: Experimental
description: Low-dose level patients received cetuximab initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance.
intervention type: Biological
intervention name: Recombinant Anti-EGFr Antibody
description: Low-dose level patients received cetuximab initial dose 100 mg/m2 and 4 weeks later 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.High-dose level patients received cetuximab initial dose 400 mg/m2 and 4 weeks later loading 400 mg/m2 and 250 mg/m2 weekly maintenance to the disease progression or unacceptable toxicity or death or withdraw informed consent.
arm group label: Recombinant Anti-EGFr Antibody
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Zhou Jianglin
phone: 86-028-67252675
email: zhoujl@kelun.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Antibodies
sharing ipd: No