<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/NCT03231176</url>
  </required_header>
  <id_info>
    <org_study_id>ASLAN001-008</org_study_id>
    <nct_id>NCT03231176</nct_id>
  </id_info>
  <brief_title>Varlitinib Plus Capecitabine in Chinese Patients With Advanced or Metastatic Biliary Tract Cancer</brief_title>
  <official_title>A Phase 2A, Single Arm, Multicentre, Study of Varlitinib Plus Capecitabine in Chinese Patients With Advanced or Metastatic Biliary Tract Cancer Who Progressed on at Least 1 Line of Systemic Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ASLAN Pharmaceuticals</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>ASLAN Pharmaceuticals</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 protocol for Varlitinib is developed for the treatment of Biliary Tract Cancer.&#xD;
      Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive&#xD;
      inhibitor of the tyrosine kinases - epidermal growth factor receptor (EGFR), human epidermal&#xD;
      growth factor receptor (HER)2, and HER4. Varlitinib may be beneficial to subjects with cancer&#xD;
      by simultaneous inhibition of these receptors. The purpose of this study is to determine the&#xD;
      safety and efficacy of Varlitinib in combination with capecitabine for the treatment of&#xD;
      Biliary Tract Cancer. Eligible patients will receive Varlitinib plus capecitabine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 19, 2017</start_date>
  <completion_date type="Actual">April 13, 2020</completion_date>
  <primary_completion_date type="Actual">July 5, 2019</primary_completion_date>
  <phase>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>Objective Response Rate (ORR)</measure>
    <time_frame>Through study duration, estimated 2 years</time_frame>
    <description>Objective Response Rate defined as the proportion of patients with a confirmed best response of partial response (PR) or complete response (CR), as defined by RECIST v1.1 criteria, based on an Independent Central Review (ICR) of radiological data.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>Through study duration, estimated 2 years</time_frame>
    <description>Progression Free Survival defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined in accordance with the RECIST v1.1 criteria and will be derived using data from the ICR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Through study duration, estimated 2 years</time_frame>
    <description>Disease control rate is defined as the number (%) of patients with a confirmed response of CR or PR, or with stable disease for a minimum of twelve weeks (- 5 days) from starting treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>Through study duration, estimated 2 years</time_frame>
    <description>The Duration of Response is defined as the time from the date of first documented response until the date of documented disease progression or death in the absence of disease progression, in the subset of patient classified as confirmed responders for the assessment of ORR. The end of response should coincide with the date of disease progression or death from any cause used for the PFS endpoint. DoR will be calculated using the ICR data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Through study duration, estimated 2 years</time_frame>
    <description>Overall Survival is defined as time from the start of treatment until death by any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of varlitinib when combined with capecitabine</measure>
    <time_frame>Through study duration, estimated 2 years</time_frame>
    <description>Incidence of AEs, categorized in accordance to CTCAE 4.03, and changes from baseline in safety parameters</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Biliary Tract Cancer</condition>
  <arm_group>
    <arm_group_label>Varlitinib and Capecitabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Varlitinib</intervention_name>
    <description>oral tablets, twice daily</description>
    <arm_group_label>Varlitinib and Capecitabine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Capecitabine</intervention_name>
    <description>oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles</description>
    <arm_group_label>Varlitinib and Capecitabine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Patients with histologically or cytologically confirmed advanced (unresectable) or&#xD;
             metastatic biliary tract cancer, including intrahepatic or extrahepatic&#xD;
             cholangiocarcinoma, gallbladder cancer and carcinoma of the Ampulla of Vater. This&#xD;
             includes clinical diagnosis of biliary tract cancer with histological confirmation of&#xD;
             adenocarcinoma.&#xD;
&#xD;
          2. Patients who have received and failed one and only one prior line of systemic&#xD;
             treatment or advanced or metastatic disease with radiologic evidence of disease&#xD;
             progression. This prior line of systemic treatment must also contain gemcitabine&#xD;
&#xD;
          3. Patients with radiographically measurable disease based on RECIST v1.1.&#xD;
&#xD;
          4. Patients with no evidence of biliary duct obstruction, unless obstruction is&#xD;
             controlled by local treatment or, in whom the biliary tree can be decompressed by&#xD;
             endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below&#xD;
             1.5 x upper level of normal (ULN).&#xD;
&#xD;
          5. Patients who are or older than 18 years of age and of or younger than 99 years of age&#xD;
             at the time when written informed consent is obtained, and are able to understand and&#xD;
             willing to sign the informed consent form.&#xD;
&#xD;
          6. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or&#xD;
             1.&#xD;
&#xD;
          7. Patients with adequate organ and hematological function:&#xD;
&#xD;
               1. Hematological function, as follows:&#xD;
&#xD;
                    -  Absolute neutrophil count (ANC) ≥ 1.5 x 109/L&#xD;
&#xD;
                    -  Platelet count ≥ 100 x 109/L&#xD;
&#xD;
               2. Renal functions, as follows:&#xD;
&#xD;
                    -  Estimated glomerular filtration rate or creatinine clearance &gt; 50&#xD;
                       mL/min/1.73m2&#xD;
&#xD;
               3. Hepatic function, as follows:&#xD;
&#xD;
                    -  Total bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
                    -  AST and ALT ≤ 5 x ULN&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients are currently on or have received anti-cancer therapy within the past 3&#xD;
             weeks.&#xD;
&#xD;
          2. Patients are currently on or have received radiation or local treatment within the&#xD;
             past 3 weeks for the target lesion(s).&#xD;
&#xD;
          3. Patients have had major surgical procedures within 14 days prior to study entry.&#xD;
&#xD;
          4. Patients have a metastatic brain lesion(s), including asymptomatic and well controlled&#xD;
             lesion(s).&#xD;
&#xD;
          5. Patients have malabsorption syndrome, diseases significantly affecting&#xD;
             gastrointestinal function, resection of the stomach or small bowel, or difficulty in&#xD;
             swallowing and retaining oral medications.&#xD;
&#xD;
          6. Patients have any history or presence of clinically significant condition which in the&#xD;
             opinion of the Investigator could jeopardize the safety of the patient or the validity&#xD;
             of the study results.&#xD;
&#xD;
          7. Patients have any history of other malignancy unless in remission for more than 1&#xD;
             year. (skin carcinoma and carcinoma-in-site of uterine cervix treated with curative&#xD;
             intent is not exclusionary).&#xD;
&#xD;
          8. Female patients are pregnant or breast feeding.&#xD;
&#xD;
          9. Patients who been previously treated with varlitinib or have been previously treated&#xD;
             with capecitabine as first line therapy for advanced or metastatic disease. For&#xD;
             patients who have previously received capecitabine as radiosensitizer or as part of&#xD;
             their adjuvant therapy and their disease has relapsed for more than 6 months after&#xD;
             their last dose of capecitabine adjuvant therapy, their capecitabine therapy will not&#xD;
             be considered as a line of systemic chemotherapy for metastatic/advanced disease, and&#xD;
             thus they can participate in the study.&#xD;
&#xD;
         10. Patients have received any investigational drug (or have used an investigational&#xD;
             device) within the last 14 days before receiving the first dose of study medication.&#xD;
&#xD;
         11. Patients have unresolved or unstable serious toxicity (≥CTCAE 4.03 Grade 2), with the&#xD;
             exception of anemia, asthenia, and alopecia, from prior administration of another&#xD;
             investigational drug and/or prior cancer treatment.&#xD;
&#xD;
         12. Patients have a known positive test for HIV, active hepatitis C, or hepatitis B&#xD;
             infection with hepatitis B virus deoxyribonucleic acid exceeding 2000 IU/mL.&#xD;
&#xD;
         13. Patients have a known history of drug addiction within last 1 year, on the basis that&#xD;
             there could be a higher risk of non-compliance to investigational product.&#xD;
&#xD;
         14. Patients need continuous treatment with proton pump inhibitors during the study&#xD;
             period.&#xD;
&#xD;
         15. Patients have a baseline corrected QT interval QTc&gt; 450 ms or patients with known long&#xD;
             QT syndrome, torsade de pointes, symptomatic ventricular tachycardia, an unstable&#xD;
             cardiac syndrome in the past 3 months before screening visit, &gt; class 2 New York Heart&#xD;
             Association heart failure, &gt; grade 2 Canadian cardiovascular society angina pectoris,&#xD;
             or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic,&#xD;
             dofetilide, or sotalol methadone.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>No.81 Hospital of The Chinese People's Liberation Army</name>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>There is 22 sites located in other cities of China, including Nanjing</name>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 26, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2017</study_first_posted>
  <last_update_submitted>November 18, 2020</last_update_submitted>
  <last_update_submitted_qc>November 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Biliary Tract Neoplasms</keyword>
  <keyword>Bile Duct Neoplasms</keyword>
  <keyword>Gallbladder Neoplasms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Biliary Tract Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capecitabine</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/NCT03231176
org study id: ASLAN001-008
nct id: NCT03231176
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This protocol for Varlitinib is developed for the treatment of Biliary Tract Cancer.
      Varlitinib (also known as ASLAN001) is a small-molecule, adenosine triphosphate competitive
      inhibitor of the tyrosine kinases - epidermal growth factor receptor (EGFR), human epidermal
      growth factor receptor (HER)2, and HER4. Varlitinib may be beneficial to subjects with cancer
      by simultaneous inhibition of these receptors. The purpose of this study is to determine the
      safety and efficacy of Varlitinib in combination with capecitabine for the treatment of
      Biliary Tract Cancer. Eligible patients will receive Varlitinib plus capecitabine.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR)
time frame: Through study duration, estimated 2 years
description: Objective Response Rate defined as the proportion of patients with a confirmed best response of partial response (PR) or complete response (CR), as defined by RECIST v1.1 criteria, based on an Independent Central Review (ICR) of radiological data.
measure: Progression-free survival (PFS)
time frame: Through study duration, estimated 2 years
description: Progression Free Survival defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined in accordance with the RECIST v1.1 criteria and will be derived using data from the ICR.
measure: Disease Control Rate (DCR)
time frame: Through study duration, estimated 2 years
description: Disease control rate is defined as the number (%) of patients with a confirmed response of CR or PR, or with stable disease for a minimum of twelve weeks (- 5 days) from starting treatment.
measure: Duration of Response (DoR)
time frame: Through study duration, estimated 2 years
description: The Duration of Response is defined as the time from the date of first documented response until the date of documented disease progression or death in the absence of disease progression, in the subset of patient classified as confirmed responders for the assessment of ORR. The end of response should coincide with the date of disease progression or death from any cause used for the PFS endpoint. DoR will be calculated using the ICR data.
measure: Overall Survival (OS)
time frame: Through study duration, estimated 2 years
description: Overall Survival is defined as time from the start of treatment until death by any cause.
measure: Safety and tolerability of varlitinib when combined with capecitabine
time frame: Through study duration, estimated 2 years
description: Incidence of AEs, categorized in accordance to CTCAE 4.03, and changes from baseline in safety parameters
arm group label: Varlitinib and Capecitabine
arm group type: Experimental
intervention type: Drug
intervention name: Varlitinib
description: oral tablets, twice daily
arm group label: Varlitinib and Capecitabine
intervention type: Drug
intervention name: Capecitabine
description: oral tablets, twice daily for 2 weeks followed by a 1-week rest period in 3-week cycles
arm group label: Varlitinib and Capecitabine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Biliary Tract Neoplasms
mesh term: Capecitabine
sharing ipd: No