Biliary Tract CancerPhase 2NCT02579616
Study of Lenvatinib (E7080) in Unresectable Biliary Tract Cancer (BTC) Who Failed Gemcitabine-based Combination Chemotherapy
A Phase 2 study testing Lenvatinib in people with Biliary Tract Cancer, run by Eisai Co., Ltd. at 7 sites in Japan.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Biliary Tract Cancer
- What is being tested?
- Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 7 sitesJapan
- Study dates
- 23 Oct 2015to 27 Feb 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
- 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
- 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
- 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
- Participants must voluntarily agree to provide written informed consent
- Participants must be willing and able to comply with all aspects of the protocol
Who cannot join
- 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
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- 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
- History of drug or alcohol dependency or abuse within the last 24 months prior to the first dose of study drug
- Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study
- 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.
- 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
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Japan7 sites
Study site
Chuo-ku, Tokyo
Study site
Ina-machi, Saitama
Study site
Kashiwa, Chiba
Study site
Koto-ku, Tokyo
Study site
Mitaka, Tokyo
Study site
Nagoya, Aichi-ken
Study site
Yokohama, Kanagawa
About this study
Official title: 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.
- Conditions
- Biliary Tract Cancer
- Being tested
- Lenvatinib
- Keywords
- Lenvatinib, E7080, Unresectable biliary tract cancer, BTC, Gemcitabine-based combination chemotherapy, Lenvima
- Medical subject headings
- Biliary Tract Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called E7080, Lenvima, Lenvatinib Mesylate
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Measured: 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
Measured: Cycle 1 Day 1: 0.5-2 hours post dose (Cycle length is 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2015 (estimated)
- Study start23 Oct 2015
- Primary completion22 Nov 2016
- Study completion27 Feb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Biliary Tract CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02579616
- Sponsor's protocol ID
- E7080-J081-215
- Status last verified
- Oct 2020
- First submitted
- 16 Oct 2015
- Last updated
- 23 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 33198671
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02579616
- Acronym / sponsor ID
- E7080-J081-215
- Conditions
- Biliary Tract Cancer
- Keywords
- Lenvatinib, E7080, Unresectable biliary tract cancer, BTC, Gemcitabine-based combination chemotherapy, Lenvima
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- Eisai Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 23 Oct 2015 (actual)
- Primary completion
- 22 Nov 2016 (actual)
- Study completion
- 27 Feb 2019 (actual)
- First posted
- 19 Oct 2015 (estimated)
- Results
- Posted 23 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 24 mg Lenvatinib | Experimental | Drug: LenvatinibParticipants 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). |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
- Measurable disease meeting the following criteria:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: E7080, Lenvima, Lenvatinib MesylateLenvatinib 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. | Drug | 24 mg Lenvatinib |
Primary outcome
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.
7 secondary outcomes
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)
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)
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)
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)
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)
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)
Plasma Concentrations of Lenvatinib
Time frame: Cycle 1 Day 1: 0.5-2 hours post dose (Cycle length is 28 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33198671Ueno 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lenvatinib in people with Biliary Tract Cancer, run by Eisai Co., Ltd. at 7 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02579616, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2020.