NCT02579616

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

Completed Phase 2 Results posted Last updated 23 December 2020

What this trial tests

Phase 2 trial testing Lenvatinib in Biliary Tract Cancer in 29 participants. Completed in 27 February 2019.

Timeline

23 October 2015

Primary endpoint
22 November 2016

27 February 2019

Quick facts

Lead sponsor	Eisai Co., Ltd.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	29
Start date	23 October 2015
Primary completion	22 November 2016
Estimated completion	27 February 2019
Sites	7 locations across Japan

Drugs / interventions tested

• Lenvatinib (LENVATINIB) — full drug profile →

Conditions studied

• Biliary Tract Cancer — all drugs for Biliary Tract Cancer →

Sponsor

Eisai Co., Ltd. — full company profile →

Who can join

20 and older, any sex, with Biliary Tract Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Primary · 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.

Group	Value	95% CI
Lenvatinib 24 mg	11.5	2.4 – 30.2

Progression-free Survival (PFS) Rate at 12 Weeks Secondary · 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.

Group	Value	95% CI
Lenvatinib 24 mg	72.2	50.4 – 85.7

Progression-free Survival (PFS) Secondary · 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.

Group	Value	95% CI
Lenvatinib 24 mg	3.19	2.79 – 7.23

Overall Survival (OS) Secondary · 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.

Group	Value	95% CI
Lenvatinib 24 mg	7.35	4.50 – 11.27

Disease Control Rate (DCR) Secondary · 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.

Group	Value	95% CI
Lenvatinib 24 mg	84.6	65.1 – 95.6

Clinical Benefit Rate (CBR) Secondary · 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.

Group	Value	95% CI
Lenvatinib 24 mg	38.5	20.2 – 59.4

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Secondary · 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)

TEAEs

Group	Value	95% CI
Lenvatinib 24 mg	26

SAEs

Group	Value	95% CI
Lenvatinib 24 mg	18

Plasma Concentrations of Lenvatinib Secondary · Cycle 1 Day 1: 0.5-2 hours post dose (Cycle length is 28 days)

Group	Value	95% CI
Lenvatinib 24 mg	3.90	NA – 782

Adverse events — posted to ClinicalTrials.gov

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). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Lenvatinib 24 mg

Serious: 18/26 (69%)

Deaths: 17/26

Serious adverse events (19 terms)

Reaction	System	Lenvatinib 24 mg
Cholangitis	Hepatobiliary disorders	—
Bile duct obstruction	Hepatobiliary disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Abdominal distension	Gastrointestinal disorders	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—
Gastrointestinal obstruction	Gastrointestinal disorders	—
Gastrointestinal perforation	Gastrointestinal disorders	—
Bile duct stenosis	Hepatobiliary disorders	—
Cholecystitis 1	Hepatobiliary disorders	—
Haemobilia	Hepatobiliary disorders	—
Jaundice cholestatic	Hepatobiliary disorders	—
Biliary tract infection	Infections and infestations	—
Lung abscess	Infections and infestations	—
Urinary tract infection	Infections and infestations	—
Anastomotic ulcer	Injury, poisoning and procedural complications	—
Completed suicide	Psychiatric disorders	—
Hydronephrosis	Renal and urinary disorders	—
Renal impairment 1	Renal and urinary disorders	—
Erythema multiforme	Skin and subcutaneous tissue disorders	—

Other adverse events (106 terms — click to expand)

Reaction	System	Lenvatinib 24 mg
Hypertension	Vascular disorders	—
Proteinuria	Renal and urinary disorders	—
Dysphonia	Respiratory, thoracic and mediastinal disorders	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Fatigue	General disorders	—
Hypothyroidism	Endocrine disorders	—
Oedema peripheral	General disorders	—
Constipation	Gastrointestinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Pyrexia	General disorders	—
Weight decreased	Investigations	—
Anaemia	Blood and lymphatic system disorders	—
Abdominal pain upper	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Rash	Skin and subcutaneous tissue disorders	—
Malaise	General disorders	—
Ascites	Gastrointestinal disorders	—
Stomatitis 4	Gastrointestinal disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—
Headache	Nervous system disorders	—
Lymphopenia	Blood and lymphatic system disorders	—
Vomiting	Gastrointestinal disorders	—
Cholangitis	Hepatobiliary disorders	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—
Hypophosphataemia	Metabolism and nutrition disorders	—
Delirium	Psychiatric disorders	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—
Alopecia	Skin and subcutaneous tissue disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Abdominal distension	Gastrointestinal disorders	—
Hepatic function abnormal	Hepatobiliary disorders	—
Gingivitis	Infections and infestations	—
Liver abscess	Infections and infestations	—
Nasopharyngitis	Infections and infestations	—
Aspartate aminotransferase increased	Investigations	—
Blood alkaline phosphatase increased	Investigations	—

Most-reported serious reactions: Cholangitis, Bile duct obstruction, Decreased appetite, Abdominal distension, Gastrointestinal haemorrhage, Gastrointestinal obstruction, Gastrointestinal perforation, Bile duct stenosis.

Data from ClinicalTrials.gov NCT02579616 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Inhibition of the fibroblast growth factor receptor (FGFR) pathway: the current landscape and barriers to clinical application.
   Chae YK, Ranganath K, Hammerman PS, Vaklavas C, et al · · 2017 · cited 231× · PMID 28030802 · DOI 10.18632/oncotarget.14109
2. Pembrolizumab combined with lenvatinib as non-first-line therapy in patients with refractory biliary tract carcinoma.
   Lin J, Yang X, Long J, Zhao S, et al · · 2020 · cited 127× · PMID 32832493 · DOI 10.21037/hbsn-20-338
3. The landscape of targeted therapies for cholangiocarcinoma: current status and emerging targets.
   Chong DQ, Zhu AX. · · 2016 · cited 81× · PMID 27102149 · DOI 10.18632/oncotarget.8775
4. Biliary tract cancers: current knowledge, clinical candidates and future challenges.
   Tariq NU, McNamara MG, Valle JW. · · 2019 · cited 79× · PMID 31015767 · DOI 10.2147/cmar.s157092
5. Phase 2 study of lenvatinib monotherapy as second-line treatment in unresectable biliary tract cancer: primary analysis results.
   Ueno M, Ikeda M, Sasaki T, Nagashima F, et al · · 2020 · cited 76× · PMID 33198671 · DOI 10.1186/s12885-020-07365-4
6. Significant response to anti-PD-1 based immunotherapy plus lenvatinib for recurrent intrahepatic cholangiocarcinoma with bone metastasis: A case report and literature review.
   Chen WX, Li GX, Hu ZN, Zhu P, et al · · 2019 · cited 34× · PMID 31702638 · DOI 10.1097/md.0000000000017832
7. Targeted therapy in biliary tract cancers-current limitations and potentials in the future.
   Sahu S, Sun W. · · 2017 · cited 33× · PMID 28480071 · DOI 10.21037/jgo.2016.09.16
8. A Retrospective Study of Lenvatinib Monotherapy or Combined With Programmed Cell Death Protein 1 Antibody in the Treatment of Patients With Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma in China.
   Zhu S, Liu C, Dong Y, Shao J, et al · · 2021 · cited 11× · PMID 34976828 · DOI 10.3389/fonc.2021.788635