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

NCT02579616 | Completed Phase 2 Results

• 1 other identifier: E7080-J081-215
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Biliary Tract Cancer

Keywords

Lenvatinib; E7080; Unresectable biliary tract cancer; BTC; Gemcitabine-based combination chemotherapy; Lenvima

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  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 Outcomes (7)

• Progression-free Survival (PFS) Rate at 12 Weeks

  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)

  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)

  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)

  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)

  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)

Study Arms (1)

24 mg Lenvatinib

EXPERIMENTAL

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

Interventions

Lenvatinib DRUG

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.

Also known as: E7080, Lenvima, Lenvatinib Mesylate

24 mg Lenvatinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically or cytologically confirmed adenocarcinoma of biliary tract cancer (intrahepatic, extrahepatic cholangiocarcinoma, gall bladder cancer, and ampulla of Vater cancer)
• Unresectable (eg, locally advanced or metastatic) BTC
• 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
• 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
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Survival expectation of 3 months or longer after beginning of study treatment
• Males or females age ≥ 20 years at the time of informed consent
• 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)
• 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

You may not qualify if:

• Any anti-cancer treatment (except BSC) within 21 days prior to the first dose of study drug
• 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)
• Ascites of moderate, severe, or requiring drainage
• Proteinuria of ≥ 2+ on dipstick testing (Grade ≤ 1 confirmed by quantitative assessment is eligible)
• Gastrointestinal malabsorption or any other condition that in the opinion of the investigator might affect the absorption of study drug
• 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
• A prolonged QT/QTc interval (QTcF \> 480 ms)
• Known to be human immunodeficiency virus (HIV) positive
• Active infection requiring systemic treatment
• 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)
• 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
• 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
• Diagnosed with meningeal carcinomatosis
• 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.
• Known intolerance to the study drug or any of the excipients

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (7)

Unknown Facility

Nagoya, Aichi-ken, Japan

Location

Unknown Facility

Kashiwa, Chiba, Japan

Location

Unknown Facility

Yokohama, Kanagawa, Japan

Location

Unknown Facility

Ina-machi, Saitama, Japan

Location

Unknown Facility

Chuo-ku, Tokyo, Japan

Location

Unknown Facility

Koto-ku, Tokyo, Japan

Location

Unknown Facility

Mitaka, Tokyo, Japan

Location

Related Publications (1)

• Ueno M, Ikeda M, Sasaki T, Nagashima F, Mizuno N, Shimizu S, Ikezawa H, Hayata N, Nakajima R, Morizane C. Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results. BMC Cancer. 2020 Nov 16;20(1):1105. doi: 10.1186/s12885-020-07365-4.

  PMID: 33198671 DERIVED

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Results Point of Contact

• Title: Inquiry Service.
• Organization: Eisai Co.,Ltd.

eisai-chiken_hotline@hhc.eisai.co.jp

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2015
• First Posted: October 19, 2015
• Study Start: October 23, 2015
• Primary Completion: November 22, 2016
• Study Completion: February 27, 2019
• Last Updated: December 23, 2020
• Results First Posted: December 23, 2020

Record last verified: 2020-10

Locations

JP (7)