Study of Lenvatinib (E7080) in Unresectable Biliary Tract Cancer (BTC) Who Failed Gemcitabine-based Combination Chemotherapy
Condition: Biliary Tract Cancer
MeSH terms: Biliary Tract Neoplasms
Intervention: Lenvatinib
Intervention description: Lenvatinib will be administered orally once daily in 28-day cycles. Participants will be treated until disease progression, unacceptable toxicity, withdrawal of consent, participant's choice, etc.
Intervention MeSH terms: Lenvatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Lenvatinib; E7080; Unresectable biliary tract cancer; BTC; Gemcitabine-based combination chemotherapy; Lenvima

Summary:

      This is a multicenter, single arm, open-label study in participants with unresectable BTC and
      disease progression or failure following one prior gemcitabine-based doublet chemotherapy
      regimen (combination of gemcitabine and cisplatin, or gemcitabine and other platinum
      agent/fluoropyrimidine agent). This study contains 3 phases: a Pre-treatment phase that will
      last within 21 days; a Treatment phase that will consist of study treatment cycles and tumor
      assessment conducted every 6-8 weeks; and a Follow-up phase that will begin immediately after
      the Off-Treatment Visit and will continue as long as the participant is alive, unless the
      participant withdraws consent, or until the End of Study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Pathologically or cytologically confirmed adenocarcinoma of biliary tract cancer
             (intrahepatic, extrahepatic cholangiocarcinoma, gall bladder cancer, and ampulla of
             Vater cancer)

          2. Unresectable (eg, locally advanced or metastatic) BTC

          3. One prior gemcitabine-based doublet chemotherapy (eg, gemcitabine and cisplatin) to
             unresectable BTC and not treated by any other chemotherapy to BTC

               -  Participants who received adjuvant chemotherapy are eligible if this therapy was
                  completed and recurrent has not been shown for 6 months after the completion of
                  the therapy

          4. Measurable disease meeting the following criteria:

               -  At least 1 lesion of ≥ 1.0 cm in the longest diameter for a non-lymph node or ≥
                  1.5 cm in the short-axis diameter for a lymph node that is serially measurable
                  according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST1.1) using
                  computerized tomography/magnetic resonance imaging (CT/MRI)

               -  Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies
                  such as radiofrequency (RF) ablation must show evidence of progressive disease
                  based on RECIST 1.1 to be deemed a target lesion

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

          6. Survival expectation of 3 months or longer after beginning of study treatment

          7. Males or females age ≥ 20 years at the time of informed consent

          8. All chemotherapy- or radiation-related toxicities must have resolved to Grade 0-1 per
             Common Terminology Criteria for Adverse Events (CTCAE v 4.03), except alopecia,
             infertility, and the adverse events listed in inclusion criteria

          9. Adequately controlled blood pressure (BP) with or without antihypertensive medications
             (defined as BP ≤ 150/90 mm Hg at Screening and no change in antihypertensive
             medications within 1 week prior to the first dose of study drug)

         10. Participants with adequate function of major organs and blood coagulation:

               -  Absolute neutrophil count (ANC) ≥ 1500/mm^3 ( ≥ 1.5×103/μl)

               -  Platelets ≥ 100,000/mm3 ( ≥ 100×10^9/L)

               -  Hemoglobin ≥ 9.0 g/dL

               -  Bilirubin ≤ 2.0 mg/dL except for unconjugated hyperbilirubinemia or Gilbert's
                  syndrome

               -  Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine
                  aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN) ( ≤ 5.0 × ULN for
                  participants with the liver metastasis)

               -  Creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula

               -  Prothrombin time-International Normalized Ratio (PT-INR) ≤ 1.5

         11. Participants must voluntarily agree to provide written informed consent

         12. Participants must be willing and able to comply with all aspects of the protocol

        Exclusion Criteria:

          1. Any anti-cancer treatment (except BSC) within 21 days prior to the first dose of study
             drug

          2. Major surgery (any surgical procedure that involves anesthesia or respiratory
             assistance) within 21 days prior to the first dose of study drug or scheduled surgery
             during the study (except for bile duct drainage)

          3. Ascites of moderate, severe, or requiring drainage

          4. Proteinuria of ≥ 2+ on dipstick testing (Grade ≤ 1 confirmed by quantitative
             assessment is eligible)

          5. Gastrointestinal malabsorption or any other condition that in the opinion of the
             investigator might affect the absorption of study drug

          6. New York Heart Association congestive heart failure of class II or above, unstable
             angina, myocardial infarction, or serious cardiac arrhythmia associated with
             significant cardiovascular impairment within the past 6 months from the first dose of
             study drug

          7. A prolonged QT/QTc interval (QTcF > 480 ms)

          8. Known to be human immunodeficiency virus (HIV) positive

          9. Active infection requiring systemic treatment

         10. Bleeding or thrombotic disorders or chronic systemic use of anticoagulants requiring
             therapeutic INR monitoring, eg, warfarin or similar agents (treatment with low
             molecular weight heparin is permitted)

         11. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5
             teaspoon) within 21 days prior to the first dose of study drug

         12. Active malignancy (except for BTC or definitively treated melanoma in-situ, basal or
             squamous cell carcinoma of the skin, carcinoma in-situ of the cervix, or early stage
             gastric/colorectal cancer) within the past 24 months prior to the first dose of study
             drug

         13. Diagnosed with meningeal carcinomatosis

         14. Participants with brain or subdural metastases are not eligible, unless they have
             completed local therapy and have discontinued the use of corticosteroids for this
             indication for at least 28 days prior to the first dose of study drug. Any signs (eg,
             radiologic) or symptoms of brain metastases must be stable for at least 28 days prior
             to the first dose of study drug.

         15. Known intolerance to the study drug or any of the excipients

         16. History of drug or alcohol dependency or abuse within the last 24 months prior to the
             first dose of study drug

         17. Any medical or other condition that in the opinion of the investigator(s) would
             preclude the participant's participation in a clinical study

         18. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
             positive human chorionic gonadotropin [hCG or B-hCG]). A separate baseline assessment
             is required if a negative screening pregnancy test was obtained more than 3 days
             before the first dose of study drug.

         19. For either males unless undergoing a successful vasectomy (confirmed azoospermia) or
             females of childbearing potential, the participant and his/her partner do not agree to
             use a medically appropriate method of contraception throughout the entire study period

               -  the use of condom, contraceptive sponge, contraceptive foam, contraceptive jelly,
                  diaphragm, or intrauterine device, otherwise using oral contraceptive
                  (percutaneous or transvaginal also allowed) for at least 28 days before the first
                  dose of study drug