<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/NCT02263950</url>
  </required_header>
  <id_info>
    <org_study_id>LON002-002</org_study_id>
    <nct_id>NCT02263950</nct_id>
  </id_info>
  <brief_title>A Phase 1/2a Study of LON002 in Subjects With Advanced Solid Tumours</brief_title>
  <acronym>LON002-002</acronym>
  <official_title>A Phase 1/2a Study of LON002 (Sublingual Artemether Spray) in Subjects With Advanced Solid Tumours.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LondonPharma Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LondonPharma Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This clinical trial will assess whether a medicine called artemether, currently used at a&#xD;
      lower dose to treat malaria, could also be useful in treating cancer. For this trial, the&#xD;
      medicine is given in a new way, as a spray under the tongue. This delivery has several&#xD;
      advantages, including better absorption into the body and it may be easier for people to&#xD;
      take. It will be prescribed to consenting patients with advanced solid tumours, every day for&#xD;
      4 months, either once or twice a day. (For this study 'advanced tumour' will mean there are&#xD;
      no other effective standard therapy options available to the patient).&#xD;
&#xD;
      The dose will be decided in Phase 1 of the study by initially testing 3 different doses of&#xD;
      the medicine in up to 21 different cancer patients, to make sure it is not too toxic or&#xD;
      causes any side effects.&#xD;
&#xD;
      After this, the highest safe dose identified in the first phase will be tested in up to 66&#xD;
      cancer patients in Phase 2 of the study, to see if the medicine is able to reduce the size of&#xD;
      their tumour or slow down its growth.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>October 2014</start_date>
  <completion_date type="Anticipated">October 2016</completion_date>
  <primary_completion_date type="Anticipated">October 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Determination of the Recommended Phase 2 Dose (RP2D) to be used in Phase 2a of the study</measure>
    <time_frame>28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number (%) of patients with clinical benefit in Phase 2a</measure>
    <time_frame>16 weeks</time_frame>
    <description>Complete or partial response at any time based on imaging&#xD;
Stable disease at 16 weeks (4 cycles); and/or&#xD;
Reduction of validated biomarkers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with Dose limiting toxicities</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP), progression free survival (PFS) and overall survival (OS).</measure>
    <time_frame>16 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">87</enrollment>
  <condition>Solid Tumours</condition>
  <arm_group>
    <arm_group_label>LON002</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>(Artemether sublingual spray)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Artemether</intervention_name>
    <description>Artemether sublingual spray at 20mg per spray. Dose escalation study design as per protocol; in Phase 1, three dose levels will be given. The Phase 2 dose will be determined from the results of Phase 1. All patients will receive 4 cycles of dosing, 28 days per cycle.</description>
    <arm_group_label>LON002</arm_group_label>
    <other_name>LON002</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects of 18 years or older at the Screening Visit.&#xD;
&#xD;
          2. Histologic and/or cytologically confirmed diagnosis of solid tumour with clinical and&#xD;
             imaging evidence that the tumour is advanced and for whom there is no effective&#xD;
             standard therapy available.&#xD;
&#xD;
          3. At least one evaluable tumour that is at least 10 mm by computerised tomography (CT)&#xD;
             scan or magnetic resonance imaging (MRI) at the pre-treatment stage&#xD;
&#xD;
          4. At least one prior systemic anti-cancer treatment and disease that is refractory or&#xD;
             progressive following treatment.&#xD;
&#xD;
          5. Eastern Co operative Oncology Group (ECOG) performance ≤ 2.&#xD;
&#xD;
          6. An adequate renal, liver and bone marrow function.&#xD;
&#xD;
          7. Women of child bearing potential (WOCBP) must have a negative pregnancy test before&#xD;
             the start of treatment.&#xD;
&#xD;
          8. Sexually active women of childbearing potential must be using an acceptable form of&#xD;
             contraception, as detailed in the protocol.&#xD;
&#xD;
          9. Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and&#xD;
             their female partner must meet the criteria defined in the protocol (i.e., not of&#xD;
             childbearing potential or practicing highly effective contraception throughout the&#xD;
             study period and for 30 days after study drug discontinuation). Those with partners&#xD;
             using hormonal contraceptives must also be using an additional approved method of&#xD;
             barrier contraception.&#xD;
&#xD;
         10. Expected life expectancy &gt; 4 months.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unwillingness or inability to provide informed consent.&#xD;
&#xD;
          2. Any evidence of severe or uncontrolled systemic diseases, infection or laboratory&#xD;
             finding that in the view of the Investigator makes it undesirable for the patient to&#xD;
             participate in the trial.&#xD;
&#xD;
          3. Allergic to artemether or other artemisinin derivatives or any of the components of&#xD;
             the sublingual formulation.&#xD;
&#xD;
          4. Pregnancy or lactation.&#xD;
&#xD;
          5. Subject had major surgery or significant traumatic injury within 4 weeks of start of&#xD;
             study drug; subject has not recovered from the side effects of any major surgery&#xD;
             (defined as requiring general anaesthesia) or subject might require major surgery&#xD;
             during the course of the study.&#xD;
&#xD;
          6. Subject has had anti-cancer treatment within 4 weeks of start of study drug, excluding&#xD;
             small field palliative irradiation which may be performed up to 2 weeks prior to start&#xD;
             of study drug.&#xD;
&#xD;
          7. Subject has had prior treatment with any investigational drug within the preceding 4&#xD;
             weeks before study start.&#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>Debashis Sarker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Guy's and St Thomas' NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mazhar Ajaz, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Royal Surrey County Hospital NHS Trust</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Daryl Bendel, MD</last_name>
    <role>Study Director</role>
    <affiliation>Xidea Solutions Ltd.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>London Pharma Ltd</last_name>
    <phone>01865 784485</phone>
    <email>davidlaskow-pooley@londonpharma.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>The Royal Surrey County Hospital</name>
      <address>
        <city>Guildford</city>
        <state>Surrey</state>
        <zip>GU2 7XX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <investigator>
      <last_name>Mazhar Ajaz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Guy's and St Thomas NHS Foundation Trust</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Debashis Sarker, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2015</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>September 4, 2015</last_update_submitted>
  <last_update_submitted_qc>September 4, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 7, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Malignant Neoplasm</keyword>
  <keyword>Artemether</keyword>
  <keyword>Sublingual</keyword>
  <keyword>Neoplastic disease</keyword>
  <keyword>Solid Tumour</keyword>
  <keyword>Anti-cancer drug</keyword>
  <keyword>Chemotherapy</keyword>
  <keyword>LON002</keyword>
  <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>Artemether</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/NCT02263950
org study id: LON002-002
nct id: NCT02263950
lead sponsor: 
has dmc: Yes
This clinical trial will assess whether a medicine called artemether, currently used at a
      lower dose to treat malaria, could also be useful in treating cancer. For this trial, the
      medicine is given in a new way, as a spray under the tongue. This delivery has several
      advantages, including better absorption into the body and it may be easier for people to
      take. It will be prescribed to consenting patients with advanced solid tumours, every day for
      4 months, either once or twice a day. (For this study 'advanced tumour' will mean there are
      no other effective standard therapy options available to the patient).

      The dose will be decided in Phase 1 of the study by initially testing 3 different doses of
      the medicine in up to 21 different cancer patients, to make sure it is not too toxic or
      causes any side effects.

      After this, the highest safe dose identified in the first phase will be tested in up to 66
      cancer patients in Phase 2 of the study, to see if the medicine is able to reduce the size of
      their tumour or slow down its growth.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of the Recommended Phase 2 Dose (RP2D) to be used in Phase 2a of the study
time frame: 28 days
measure: Number (%) of patients with clinical benefit in Phase 2a
time frame: 16 weeks
description: Complete or partial response at any time based on imaging
Stable disease at 16 weeks (4 cycles); and/or
Reduction of validated biomarkers
measure: Number of subjects with Dose limiting toxicities
time frame: 16 weeks
measure: Time to progression (TTP), progression free survival (PFS) and overall survival (OS).
time frame: 16 weeks
arm group label: LON002
arm group type: Experimental
description: (Artemether sublingual spray)
intervention type: Drug
intervention name: Artemether
description: Artemether sublingual spray at 20mg per spray. Dose escalation study design as per protocol; in Phase 1, three dose levels will be given. The Phase 2 dose will be determined from the results of Phase 1. All patients will receive 4 cycles of dosing, 28 days per cycle.
arm group label: LON002
other name: LON002
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Debashis Sarker, MD
role: Principal Investigator
affiliation: Guy's and St Thomas' NHS Foundation Trust
last name: Mazhar Ajaz, MD
role: Principal Investigator
affiliation: Royal Surrey County Hospital NHS Trust
last name: Daryl Bendel, MD
role: Study Director
affiliation: Xidea Solutions Ltd.
last name: London Pharma Ltd
phone: 01865 784485
email: davidlaskow-pooley@londonpharma.com
facility: 
status: Not yet recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Artemether