Study of Lenvatinib (E7080) in Unresectable Biliary Tract Cancer (BTC) Who Failed Gemcitabine-based Combination Chemotherapy

December 1, 2020 updated by: Eisai Co., Ltd.

An Open-Label, Multicenter Phase 2 Study of E7080/ LENVIMA (Lenvatinib Mesylate) in Subjects With Unresectable Biliary Tract Cancer Who Failed Gemcitabine-based Combination Chemotherapy

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

29

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
    • Aichi
      • Nagoya, Aichi, Japan
    • Chiba
      • Kashiwa, Chiba, Japan
    • Kanagawa
      • Yokohama, Kanagawa, Japan
    • Saitama
      • Ina-machi, Saitama, Japan
    • Tokyo
      • Chuo-ku, Tokyo, Japan
      • Koto-ku, Tokyo, Japan
      • Mitaka, Tokyo, Japan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 24 mg Lenvatinib
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).
Drug: Lenvatinib
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.
Other Names:
  • E7080
  • Lenvima
  • Lenvatinib Mesylate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: From the date of first dose of study drug to the date of last documentation of disease progression or date of death from any cause, whichever occurred first (up to approximately 1 year 1 month)
ORR was assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR was defined as the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). Confirmation of CR or PR was performed at least 28 days following the initial achievement of the response.
From the date of first dose of study drug to the date of last documentation of disease progression or date of death from any cause, whichever occurred first (up to approximately 1 year 1 month)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Rate at 12 Weeks
Time Frame: From the date of first dose to the date of last documentation of disease progression or death from any cause, whichever occurred first (up to Week 12)
PFS was assessed by the investigator based on RECIST 1.1. PFS was defined as the time from the date of first dose to the date of last documentation of disease progression or death from any cause, whichever occurred first. PFS rate was cumulative probability for event-free participants at 12 weeks. PFS rate at 12 weeks was calculated using Kaplan-Meier method.
From the date of first dose to the date of last documentation of disease progression or death from any cause, whichever occurred first (up to Week 12)
Progression-free Survival (PFS)
Time Frame: From the date of first dose of study drug to the date of last documentation of disease progression or date of death from any cause, whichever occurred first (up to approximately 3 years 4 months)
PFS was assessed by the investigator based on RECIST 1.1. PFS was defined as the time from the date of first dose to the date of last documentation of disease progression or date of death from any cause, whichever occurred first. For participants who did not have an event, PFS were censored. PFS was calculated using Kaplan-Meier method.
From the date of first dose of study drug to the date of last documentation of disease progression or date of death from any cause, whichever occurred first (up to approximately 3 years 4 months)
Overall Survival (OS)
Time Frame: From the date of first dose of study drug to the date of death from any cause (up to approximately 3 years 4 months)
OS was defined as the time from the date of first dose to the date of death from any cause. For the participants who were alive or unknown, OS was censored on the last date participant was known to be event-free or date of data-cut-off. OS was calculated using the Kaplan-Meier method.
From the date of first dose of study drug to the date of death from any cause (up to approximately 3 years 4 months)
Disease Control Rate (DCR)
Time Frame: From the date of first dose of study drug to the date of last documentation of disease progression or date of death from any cause, whichever occurred first (up to approximately 3 years 4 months)
DCR was assessed by the investigator based on RECIST 1.1. DCR was defined as the percentage of participants whose BOR was CR, PR or SD.
From the date of first dose of study drug to the date of last documentation of disease progression or date of death from any cause, whichever occurred first (up to approximately 3 years 4 months)
Clinical Benefit Rate (CBR)
Time Frame: From the date of first dose of study drug to the date of the last documentation of disease progression or death from any cause, whichever occurred first (up to approximately 3 years 4 months)
CBR was assessed by the investigator based on RECIST 1.1.CBR was defined as percentage of participants with BOR of CR, PR or durable SD. Durable SD: Durable SD: duration of SD greater than or equal to (>=23) weeks.
From the date of first dose of study drug to the date of the last documentation of disease progression or death from any cause, whichever occurred first (up to approximately 3 years 4 months)
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: From signing of informed consent form to 30 days after the decision to discontinue study treatment or 30 days after last dose of study drug, whichever comes later (up to approximately 3 years 4 months)
From signing of informed consent form to 30 days after the decision to discontinue study treatment or 30 days after last dose of study drug, whichever comes later (up to approximately 3 years 4 months)
Plasma Concentrations of Lenvatinib
Time Frame: Cycle 1 Day 1: 0.5-2 hours post dose (Cycle length is 28 days)
Cycle 1 Day 1: 0.5-2 hours post dose (Cycle length is 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eisai Co., Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 23, 2015

Primary Completion (Actual)

November 22, 2016

Study Completion (Actual)

February 27, 2019

Study Registration Dates

First Submitted

October 16, 2015

First Submitted That Met QC Criteria

October 16, 2015

First Posted (Estimate)

October 19, 2015

Study Record Updates

Last Update Posted (Actual)

December 23, 2020

Last Update Submitted That Met QC Criteria

December 1, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • E7080-J081-215

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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