<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/NCT03009214</url>
  </required_header>
  <id_info>
    <org_study_id>AMC303-01</org_study_id>
    <nct_id>NCT03009214</nct_id>
  </id_info>
  <brief_title>A Safety and Pharmacokinetic Phase I/Ib Study of AMC303 in Patients With Solid Tumours</brief_title>
  <official_title>A Safety, Tolerability and Pharmacokinetic Dose Escalation and Expansion, Phase I/Ib Study of AMC303 as Monotherapy in Patients With Advanced or Metastatic, Malignant Solid Tumour of Epithelial Origin</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>amcure GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>amcure GmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a two part Phase I/Ib, open-label, non-randomized and multi-center, dose escalation&#xD;
      study with a 3+3 design (Part 1) and an expansion cohort at the Maximum Tolerated Dose&#xD;
      (MTD)/Recommended Phase 2 Dose (RP2D) (Part 2). If MTD is not reached in Part 1, RP2D will be&#xD;
      determined after completion of Part 1 considering safety and tolerability, also beyond the&#xD;
      dose limiting toxicity (DLT) period, pharmacokinetic (PK) and pharmacodynamic (PD) results.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">May 7, 2021</completion_date>
  <primary_completion_date type="Actual">July 28, 2020</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>Safety and tolerability of AMC303</measure>
    <time_frame>6 months</time_frame>
    <description>Number of patients with treatment-related adverse events as assessed by CTCAE v4.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic properties of AMC303 (Cmax)</measure>
    <time_frame>2 days</time_frame>
    <description>Determine maximum plasma concentration (Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic properties of AMC303 (AUC)</measure>
    <time_frame>2 days</time_frame>
    <description>Determine systemic exposure (AUC) after intravenous infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic properties of AMC303 (t1/2)</measure>
    <time_frame>2 days</time_frame>
    <description>Determine half-life of AMC303 after intravenous infusion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate of treatment with AMC303 in patients with metastatic solid tumors</measure>
    <time_frame>12 months</time_frame>
    <description>Determination of the complete response (CR) and partial response (PR) in patients treated with AMC303</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">55</enrollment>
  <condition>Malignant Solid Tumor</condition>
  <arm_group>
    <arm_group_label>AMC303</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>cohorts will receive ascending doses of AMC303 as intravenous infusion&#xD;
Planned doses are:&#xD;
0.1 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 4 mg/kg, 10 mg/kg and 20 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMC303</intervention_name>
    <description>AMC303 is a CD44v6 inhibitor blocking receptor tyrosine kinase (RTK) pathways</description>
    <arm_group_label>AMC303</arm_group_label>
    <other_name>CD44v6 inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed and documented, advanced or metastatic, accessible malignant&#xD;
             solid tumour of epithelial origin and for which no standard therapy exists or standard&#xD;
             therapy has failed.&#xD;
&#xD;
          2. Presence of a measurable tumour according to RECIST 1.1. criteria&#xD;
&#xD;
          3. At least 4 weeks from the completion of any previous cytotoxic chemotherapy, 6 weeks&#xD;
             from biological therapy (monoclonal antibodies) or cancer immunotherapy (immune&#xD;
             checkpoint modulators) or 2 weeks from targeted therapy (receptor tyrosine kinase&#xD;
             inhibitors) at time of administration of AMC303.&#xD;
&#xD;
          4. Male or female patients, at least 18 years of age&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1&#xD;
&#xD;
          6. Life expectancy &gt; 12 weeks.&#xD;
&#xD;
          7. Adequate haematological function defined as&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt; 1,500 / µL&#xD;
&#xD;
               -  Platelets &gt; 100,000 / µL&#xD;
&#xD;
               -  Haemoglobin &gt; 9 g /dL.&#xD;
&#xD;
          8. Adequate renal function defined as&#xD;
&#xD;
               -  Glomerular filtration rate (GFR) ≥ 50 ml/min according to local laboratory&#xD;
                  standard or&#xD;
&#xD;
               -  Serum creatinine &lt; 1.5 mg / dL.&#xD;
&#xD;
          9. Adequate hepatic function defined as&#xD;
&#xD;
               -  Total bilirubin &lt; 1.5x institutional upper limit of normal (ULN)&#xD;
&#xD;
               -  AST, ALT ≤ 3x institutional ULN or &lt; 5x institutional ULN if known hepatic&#xD;
                  metastases&#xD;
&#xD;
               -  Alkaline phosphatase &lt; 3x institutional ULN or &lt; 5x institutional ULN if known&#xD;
                  hepatic metastases.&#xD;
&#xD;
         10. Patient may have central nervous system (CNS) involvement if metastases have been&#xD;
             treated and are stable at least 4 weeks after completion of radiation therapy and/or&#xD;
             surgery. Stable disease is defined as absence of new neurological symptoms, absence of&#xD;
             the need for steroid therapy and radiographic confirmation of stable disease.&#xD;
             Radiographic confirmation of stable disease 4 weeks after completion of radiation&#xD;
             therapy is not required unless indicated by neurological examination.&#xD;
&#xD;
         11. All female subjects will be considered to be of childbearing potential unless they are&#xD;
             postmenopausal (at least 12 months consecutive amenorrhea, in the appropriate age&#xD;
             group and without other known or suspected cause), or have been sterilized surgically.&#xD;
             For female participants and female partners of childbearing potential, willingness and&#xD;
             able to use two forms of highly effective contraception methods (e.g. oral&#xD;
             contraceptive and condom, intra-uterine device and condom) while on study and for 30&#xD;
             days after the last study treatment. For male participants or male partners of&#xD;
             childbearing potential, willingness and able to use two forms of highly effective&#xD;
             contraception methods (e.g. oral contraceptive and condom, intra-uterine device and&#xD;
             condom,) while on study and for three months after the last study treatment.&#xD;
&#xD;
         12. Provision of signed Informed Consent prior to any study related procedure being&#xD;
             performed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Receipt of any other investigational agent within 28 days prior to first&#xD;
             administration of AMC303. Investigational monoclonal antibodies must not be given&#xD;
             within 6 weeks before treatment start with AMC303.&#xD;
&#xD;
          2. Enrolment in another clinical study with an investigational drug&#xD;
&#xD;
          3. Presence of residual toxicities of CTCAE Grade &gt; 1 after prior anti-tumour therapy&#xD;
             within 2 weeks of first treatment with AMC303 with the exception of Grade 3 alopecia&#xD;
             and infusion site reactions&#xD;
&#xD;
          4. Severe concurrent illness or psychiatric illness/social situation that would limit&#xD;
             compliance with study requirements&#xD;
&#xD;
          5. Anticipation of major surgical procedures within first 4 weeks of first dose&#xD;
&#xD;
          6. Pregnancy or breast-feeding as determined by a serum pregnancy test (β-HCG) at&#xD;
             screening prior to administration of AMC303 and willingness to father a child or to&#xD;
             become pregnant&#xD;
&#xD;
          7. Untreated acute infectious disease&#xD;
&#xD;
          8. Patient is known to be suffering from Acquired Immune Deficiency Syndrome (AIDS) or is&#xD;
             known to be HIV seropositive without AIDS defining disease&#xD;
&#xD;
          9. Known chronic hepatitis B or C.&#xD;
&#xD;
         10. History of allergic reactions attributed to compounds of similar chemical or&#xD;
             biological composition to AMC303.&#xD;
&#xD;
         11. Evidence of any other medical conditions that in the opinion of the investigator may&#xD;
             interfere with the planned treatment, affect patient compliance or place the patient&#xD;
             at high risk from treatment-related complications&#xD;
&#xD;
         12. Previous malignant disease other than the target malignancy to be investigated within&#xD;
             the last 5 years with the exception of basal or squamous carcinoma of the skin or&#xD;
             cervical carcinoma in situ&#xD;
&#xD;
         13. Legal incapacity or limited legal capacity&#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>Klaus Dembowsky, MD PhD</last_name>
    <role>Study Chair</role>
    <affiliation>amcure GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Jules Bordet Instiut</name>
      <address>
        <city>Brussels</city>
        <zip>1000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Brussel</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Català d'Oncologia, Hospital Duran i Reynals</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Barcelona</state>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vall d'Hebron Institute of Oncology (VHIO)</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Madrid-CIOCC, Centro Integral Oncológico Clara Campal</name>
      <address>
        <city>Madiedo</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Investigación Sanitaria INCLIVA, Hospital Clínico de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Spain</country>
  </location_countries>
  <link>
    <url>http://www.amcure.com</url>
    <description>Homepage amcure</description>
  </link>
  <reference>
    <citation>Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A, Orian-Rousseau V. Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling. Gastroenterology. 2016 Feb;150(2):513-25.e10. doi: 10.1053/j.gastro.2015.10.020. Epub 2015 Oct 24.</citation>
    <PMID>26597578</PMID>
  </reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>November 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 31, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <last_update_submitted>May 7, 2021</last_update_submitted>
  <last_update_submitted_qc>May 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>solid epithelial cancer</keyword>
  <keyword>CD44v6</keyword>
  <keyword>c-Met</keyword>
  <keyword>VEGFR-2</keyword>
  <keyword>RON</keyword>
  <keyword>receptor tyrosine kinase</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</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/NCT03009214
org study id: AMC303-01
nct id: NCT03009214
lead sponsor: 
has dmc: Yes
This is a two part Phase I/Ib, open-label, non-randomized and multi-center, dose escalation
      study with a 3+3 design (Part 1) and an expansion cohort at the Maximum Tolerated Dose
      (MTD)/Recommended Phase 2 Dose (RP2D) (Part 2). If MTD is not reached in Part 1, RP2D will be
      determined after completion of Part 1 considering safety and tolerability, also beyond the
      dose limiting toxicity (DLT) period, pharmacokinetic (PK) and pharmacodynamic (PD) results.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of AMC303
time frame: 6 months
description: Number of patients with treatment-related adverse events as assessed by CTCAE v4.0
measure: Pharmacokinetic properties of AMC303 (Cmax)
time frame: 2 days
description: Determine maximum plasma concentration (Cmax)
measure: Pharmacokinetic properties of AMC303 (AUC)
time frame: 2 days
description: Determine systemic exposure (AUC) after intravenous infusion
measure: Pharmacokinetic properties of AMC303 (t1/2)
time frame: 2 days
description: Determine half-life of AMC303 after intravenous infusion
measure: Response rate of treatment with AMC303 in patients with metastatic solid tumors
time frame: 12 months
description: Determination of the complete response (CR) and partial response (PR) in patients treated with AMC303
arm group label: AMC303
arm group type: Experimental
description: cohorts will receive ascending doses of AMC303 as intravenous infusion
Planned doses are:
0.1 mg/kg, 0.5 mg/kg, 1.5 mg/kg, 4 mg/kg, 10 mg/kg and 20 mg/kg
intervention type: Drug
intervention name: AMC303
description: AMC303 is a CD44v6 inhibitor blocking receptor tyrosine kinase (RTK) pathways
arm group label: AMC303
other name: CD44v6 inhibitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Klaus Dembowsky, MD PhD
role: Study Chair
affiliation: amcure GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Belgium
country: Spain
url: http://www.amcure.com
description: Homepage amcure
citation: Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A, Orian-Rousseau V. Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling. Gastroenterology. 2016 Feb;150(2):513-25.e10. doi: 10.1053/j.gastro.2015.10.020. Epub 2015 Oct 24.
PMID: 26597578
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No