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Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer

Primary Purpose

Advanced or Metastatic Biliary Tract Cancer

Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Varlitinib
Capecitabine
Sponsored by
ASLAN Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced or Metastatic Biliary Tract Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.
  2. Are able to understand and willing to sign the informed consent form.
  3. Have histologically confirmed diagnoses of relapsed, locally advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and carcinoma of Ampulla of Vater.
  4. Have eligible tumor tissue (archival or fresh) for the evaluation of relevant primary endpoints.

    (Note: For patients without eligible tumor tissue, a discussion with the sponsor is mandatory).

  5. Have radiographically measurable disease as determined by the investigator based on the RECIST v1.1 criteria.
  6. Have no evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN).
  7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  8. Have an estimated life expectancy of more than 3 months, at the time of screening.
  9. Have adequate organ and hematological function:

    1. Hematological function, as follows:

      • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
      • Platelet count ≥ 100 x 109/L
    2. Renal functions, as follows:

      • estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) > 50 mL/min/1.73m2
    3. Hepatic function, as follows:

      • Total bilirubin ≤ 1.5 x ULN
      • aspartate aminotransferase and alanine aminotransferase ≤ 5 x ULN

Exclusion Criteria:

  1. Have received systemic anti-cancer treatment except (neo-) adjuvant therapy for early stage disease.
  2. Are currently on or have received radiation or local treatment within the past 4 weeks for the target lesion(s), prior to screening.
  3. Had undergone major surgical procedures within 28 days prior to study cycle 1 day 1.
  4. Have a metastatic brain lesion(s), including asymptomatic and well controlled lesion(s).
  5. Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, or difficulty in swallowing and retaining oral medications.
  6. Have any history of other malignancy unless in remission for more than 1 year (skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary).
  7. Are female patients who are pregnant or breast feeding.
  8. Have been previously treated with varlitinib or capecitabine.
  9. Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication.
  10. Have unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior anti-cancer treatment.
  11. Have a known positive test for human immunodeficiency virus, active viral hepatitis C, viral hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL.
  12. Have a known history of drug addiction within last 1 year, on the basis of which there could be a higher risk of non-compliance to study treatment.
  13. Need continuous treatment with proton pump inhibitors during the study period.
  14. Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or with a history of interstitial lung disease or current interstitial lung disease.
  15. Have any history or presence of clinically significant condition which in the opinion of the investigator could jeopardize the safety of the patient or the validity of the study results.
  16. Have a baseline corrected QT interval > 450 ms or patients with known long QT syndrome, torsade de pointes, symptomatic ventricular tachycardia, unstable cardiac syndrome in the past 3 months before screening visit, > class 2 NYHA (The New York Heart Association Functional Classification heart failure), > grade 2 CCS (the Canadian Cardiovascular Society Guidelines) angina pectoris, or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, or sotalol methadone.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Varlitinib given in combination with capecitabine

    Arm Description

    PO varlitinib 300 mg BID PO capecitabine 1000 mg/m2 BID

    Outcomes

    Primary Outcome Measures

    Objective Response Rate (ORR)
    Number (%) of patients with at least one visit response of CR or PR. Tumor evaluations will continue until the earlier of disease progression or starting a subsequent anti-cancer therapy.
    Biomarker
    Use Next generation sequencing/Immunohistochemistry to identify relationships between response to varlitinib and mutations or overexpression in human epidermal growth factor receptor (HER) receptors and the downstream signaling proteins, as well as, mutations in selected cancer pathways.

    Secondary Outcome Measures

    Progression-free survival (PFS)
    Defined as the time from start of treatment until the date of objective disease progression or death (by any cause in the absence of disease progression).
    Overall survival (OS)
    Defined as the time from start of treatment until death by any cause.
    Duration of response (DoR)
    Defined as the time, in days, from the first recorded achievement of a response (PR or above) until time of objective disease progression in the subset of patients classified as responders in the assessment of ORR
    Disease control rate (DCR)
    Defined as the proportion of patients with a best response of stable disease maintained for at least 12 weeks (-5 days), PR or CR as defined by RECIST v1.1 criteria.
    Objective response rate (ORR)
    Defined as the proportion of patients with a best objective response (BOR) of complete response (CR) or partial response (PR), as assessed by the investigator defined by the RECIST v1.1 criteria.
    Incidence of Adverse Events and changes from baseline in safety parameters
    Incidence of Adverse Events, categorized in accordance to CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests).

    Full Information

    First Posted
    April 21, 2017
    Last Updated
    May 21, 2018
    Sponsor
    ASLAN Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT03129074
    Brief Title
    Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer
    Official Title
    A Phase 2, Single Arm Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer as First-line Systemic Therapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    May 2018
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    sponsor decision
    Study Start Date
    May 2018 (Anticipated)
    Primary Completion Date
    March 2020 (Anticipated)
    Study Completion Date
    September 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    ASLAN Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The purpose of the study is to assess the efficacy of varlitinib in combination with capecitabine as measured by objective response rate (ORR) assessed by independent central review (ICR), based on RECIST v1.1 criteria.
    Detailed Description
    Also to explore the role of biomarkers as predictors of response and clinical benefit with varlitinib

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Advanced or Metastatic Biliary Tract Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Varlitinib given in combination with capecitabine
    Arm Type
    Experimental
    Arm Description
    PO varlitinib 300 mg BID PO capecitabine 1000 mg/m2 BID
    Intervention Type
    Drug
    Intervention Name(s)
    Varlitinib
    Intervention Description
    everyday
    Intervention Type
    Drug
    Intervention Name(s)
    Capecitabine
    Intervention Description
    from Day 1 to Day 14 followed by 7-day of rest period, every 21 days.
    Primary Outcome Measure Information:
    Title
    Objective Response Rate (ORR)
    Description
    Number (%) of patients with at least one visit response of CR or PR. Tumor evaluations will continue until the earlier of disease progression or starting a subsequent anti-cancer therapy.
    Time Frame
    Through study duration, estimated 3 years
    Title
    Biomarker
    Description
    Use Next generation sequencing/Immunohistochemistry to identify relationships between response to varlitinib and mutations or overexpression in human epidermal growth factor receptor (HER) receptors and the downstream signaling proteins, as well as, mutations in selected cancer pathways.
    Time Frame
    Through study duration, estimated 3 years
    Secondary Outcome Measure Information:
    Title
    Progression-free survival (PFS)
    Description
    Defined as the time from start of treatment until the date of objective disease progression or death (by any cause in the absence of disease progression).
    Time Frame
    Through study duration, estimated 3 years
    Title
    Overall survival (OS)
    Description
    Defined as the time from start of treatment until death by any cause.
    Time Frame
    Through study duration, estimated 3 years
    Title
    Duration of response (DoR)
    Description
    Defined as the time, in days, from the first recorded achievement of a response (PR or above) until time of objective disease progression in the subset of patients classified as responders in the assessment of ORR
    Time Frame
    Through study duration, estimated 3 years
    Title
    Disease control rate (DCR)
    Description
    Defined as the proportion of patients with a best response of stable disease maintained for at least 12 weeks (-5 days), PR or CR as defined by RECIST v1.1 criteria.
    Time Frame
    Through study duration, estimated 3 years
    Title
    Objective response rate (ORR)
    Description
    Defined as the proportion of patients with a best objective response (BOR) of complete response (CR) or partial response (PR), as assessed by the investigator defined by the RECIST v1.1 criteria.
    Time Frame
    Through study duration, estimated 3 years
    Title
    Incidence of Adverse Events and changes from baseline in safety parameters
    Description
    Incidence of Adverse Events, categorized in accordance to CTCAE 4.03 and changes from baseline in safety parameters (including vital signs, ECG parameters, clinical laboratory tests).
    Time Frame
    Through study duration, estimated 3 years

    10. Eligibility

    Sex
    All
    Gender Based
    Yes
    Gender Eligibility Description
    Are of or older than the legal age in the respective countries at the time when written informed consent is obtained.
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Are of or older than the legal age in the respective countries at the time when written informed consent is obtained. Are able to understand and willing to sign the informed consent form. Have histologically confirmed diagnoses of relapsed, locally advanced (unresectable) or metastatic biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer and carcinoma of Ampulla of Vater. Have eligible tumor tissue (archival or fresh) for the evaluation of relevant primary endpoints. (Note: For patients without eligible tumor tissue, a discussion with the sponsor is mandatory). Have radiographically measurable disease as determined by the investigator based on the RECIST v1.1 criteria. Have no evidence of biliary duct obstruction, unless obstruction is controlled by local treatment or, in whom the biliary tree can be decompressed by endoscopic or percutaneous stenting with subsequent reduction in bilirubin to below 1.5 x upper level of normal (ULN). Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Have an estimated life expectancy of more than 3 months, at the time of screening. Have adequate organ and hematological function: Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Platelet count ≥ 100 x 109/L Renal functions, as follows: estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) > 50 mL/min/1.73m2 Hepatic function, as follows: Total bilirubin ≤ 1.5 x ULN aspartate aminotransferase and alanine aminotransferase ≤ 5 x ULN Exclusion Criteria: Have received systemic anti-cancer treatment except (neo-) adjuvant therapy for early stage disease. Are currently on or have received radiation or local treatment within the past 4 weeks for the target lesion(s), prior to screening. Had undergone major surgical procedures within 28 days prior to study cycle 1 day 1. Have a metastatic brain lesion(s), including asymptomatic and well controlled lesion(s). Have malabsorption syndrome, diseases significantly affecting gastrointestinal function, or difficulty in swallowing and retaining oral medications. Have any history of other malignancy unless in remission for more than 1 year (skin carcinoma and carcinoma-in-site of uterine cervix treated with curative intent is not exclusionary). Are female patients who are pregnant or breast feeding. Have been previously treated with varlitinib or capecitabine. Have received any investigational drug (or have used an investigational device) within the last 14 days before receiving the first dose of study medication. Have unresolved or unstable serious toxicity (≥ CTCAE 4.03 Grade 2), with the exception of anemia, asthenia, and alopecia, from prior administration of another investigational drug and/or prior anti-cancer treatment. Have a known positive test for human immunodeficiency virus, active viral hepatitis C, viral hepatitis B infection with hepatitis B virus DNA exceeding 2000 IU/mL. Have a known history of drug addiction within last 1 year, on the basis of which there could be a higher risk of non-compliance to study treatment. Need continuous treatment with proton pump inhibitors during the study period. Have a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, or with a history of interstitial lung disease or current interstitial lung disease. Have any history or presence of clinically significant condition which in the opinion of the investigator could jeopardize the safety of the patient or the validity of the study results. Have a baseline corrected QT interval > 450 ms or patients with known long QT syndrome, torsade de pointes, symptomatic ventricular tachycardia, unstable cardiac syndrome in the past 3 months before screening visit, > class 2 NYHA (The New York Heart Association Functional Classification heart failure), > grade 2 CCS (the Canadian Cardiovascular Society Guidelines) angina pectoris, or receiving quinidine, procainamide, disopyramide, amiodarone, dronedarone, arsenic, dofetilide, or sotalol methadone.

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Study of Varlitinib Plus Capecitabine in Patients With Advanced or Metastatic Biliary Tract Cancer

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