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

• ClinicalTrials.gov Identifier: NCT02579616
• Recruitment Status: Completed
• First Posted: October 19, 2015
• Results First Posted: December 23, 2020
• Last Update Posted: December 23, 2020
• Sponsor: Eisai Co., Ltd.
• Information provided by (Responsible Party): Eisai Inc. ( Eisai Co., Ltd. )

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Biliary Tract Cancer
• Intervention: Drug: Lenvatinib
• Enrollment: 29

Participant Flow

Recruitment Details	Participants took part in the study at 7 investigative sites in Japan from 23 Oct 2015 to 27 Feb 2019.
Pre-assignment Details	A total of 29 participants were screened and enrolled, of which 3 were screen failures and 26 were treated in the study.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description	Participants received lenvatinib 24 milligram (mg) capsules, orally, once daily in 28-days treatment cycles until disease progression, adverse events (AEs), withdrawal of consent, or participant's choice (up to Cycle 40).
Period Title: Overall Study
Started	29
Treated	26
Completed	26
Not Completed	3
Reason Not Completed
Participants did not receive treatment	3

Baseline Characteristics

Arm/Group Title		Lenvatinib 24 mg
Arm/Group Description		Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Baseline Participants		26
Baseline Analysis Population Description		The full analysis set (FAS) included the group of participants who received at least one dose of study drug.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	26 participants
		62.1 (9.48)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Female	11 42.3%
	Male	15 57.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Hispanic or Latino	0 0.0%
	Not Hispanic or Latino	26 100.0%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	American Indian or Alaska Native	0 0.0%
	Asian	26 100.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	0 0.0%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The FAS included the group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participant
	11.5; (2.4 to 30.2)

2. Secondary Outcome

Title	Progression-free Survival (PFS) Rate at 12 Weeks
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The FAS included the group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participant
	72.2; (50.4 to 85.7)

3. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The FAS included the group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Median (95% Confidence Interval); Unit of Measure: months
	3.19; (2.79 to 7.23)

4. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The FAS included the group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Median (95% Confidence Interval); Unit of Measure: months
	7.35; (4.50 to 11.27)

5. Secondary Outcome

Title	Disease Control Rate (DCR)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The FAS included the group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participant
	84.6; (65.1 to 95.6)

6. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	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.
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)

Outcome Measure Data

Analysis Population Description

The FAS included the group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participant
	38.5; (20.2 to 59.4)

7. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	[Not Specified]
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)

Outcome Measure Data

Analysis Population Description

The safety analysis set included group of participants who received at least one dose of study drug.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Measure Type: Number; Unit of Measure: participants
TEAEs	26
SAEs	18

8. Secondary Outcome

Title	Plasma Concentrations of Lenvatinib
Description	[Not Specified]
Time Frame	Cycle 1 Day 1: 0.5-2 hours post dose (Cycle length is 28 days)

Outcome Measure Data

Analysis Population Description

The safety analysis set included group of participants who received at least one dose of study drug. The safety analysis set was used for plasma lenvatinib concentration calculation.

Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description:	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
Overall Number of Participants Analyzed	26
Median (Full Range); Unit of Measure: nanogram per milliliter (ng/mL)
	3.90 [1]; (NA to 782)

[1]

The lower limit value was not estimable as it was below the limit of quantification.

Adverse Events

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)
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Lenvatinib 24 mg
Arm/Group Description	Participants received lenvatinib 24 mg capsules, orally, once daily in 28-days treatment cycles until disease progression, AEs, withdrawal of consent, or participant's choice (up to Cycle 40).
All-Cause Mortality
	Lenvatinib 24 mg
	Affected / at Risk (%)
Total	17/26 (65.38%)
Serious Adverse Events
	Lenvatinib 24 mg
	Affected / at Risk (%)
Total	18/26 (69.23%)
Gastrointestinal disorders
Abdominal distension † 1	1/26 (3.85%)
Gastrointestinal haemorrhage † 1	1/26 (3.85%)
Gastrointestinal obstruction † 1	1/26 (3.85%)
Gastrointestinal perforation † 1	1/26 (3.85%)
Hepatobiliary disorders
Bile duct obstruction † 1	2/26 (7.69%)
Bile duct stenosis † 1	1/26 (3.85%)
Cholangitis † 1	4/26 (15.38%)
Cholecystitis 1 † 1	1/26 (3.85%)
Haemobilia † 1	1/26 (3.85%)
Jaundice cholestatic † 1	1/26 (3.85%)
Infections and infestations
Biliary tract infection † 1	1/26 (3.85%)
Lung abscess † 1	1/26 (3.85%)
Urinary tract infection † 1	1/26 (3.85%)
Injury, poisoning and procedural complications
Anastomotic ulcer † 1	1/26 (3.85%)
Metabolism and nutrition disorders
Decreased appetite † 1	2/26 (7.69%)
Psychiatric disorders
Completed suicide † 1	1/26 (3.85%)
Renal and urinary disorders
Hydronephrosis † 1	1/26 (3.85%)
Renal impairment 1 † 1	1/26 (3.85%)
Skin and subcutaneous tissue disorders
Erythema multiforme † 1	1/26 (3.85%)
1 Term from vocabulary, MedDRA 21.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Lenvatinib 24 mg
	Affected / at Risk (%)
Total	26/26 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	6/26 (23.08%)
Disseminated intravascular coagulation † 1	1/26 (3.85%)
Leukopenia † 1	1/26 (3.85%)
Lymphopenia † 1	3/26 (11.54%)
Neutropenia † 1	1/26 (3.85%)
Thrombocytopenia † 1	14/26 (53.85%)
Endocrine disorders
Hypoparathyroidism † 1	1/26 (3.85%)
Hypothyroidism † 1	12/26 (46.15%)
Eye disorders
Conjunctival haemorrhage 1 † 1	1/26 (3.85%)
Gastrointestinal disorders
Abdominal distension † 1	2/26 (7.69%)
Abdominal pain † 1	1/26 (3.85%)
Abdominal pain upper † 1	6/26 (23.08%)
Ascites † 1	4/26 (15.38%)
Cheilitis † 1	1/26 (3.85%)
Constipation † 1	8/26 (30.77%)
Diarrhoea † 1	8/26 (30.77%)
Dry mouth † 1	1/26 (3.85%)
Fistula of small intestine † 1	1/26 (3.85%)
Gastroduodenal ulcer † 1	1/26 (3.85%)
Gastrointestinal haemorrhage † 1	1/26 (3.85%)
Nausea † 1	6/26 (23.08%)
Pancreatitis † 1	1/26 (3.85%)
Stomatitis 4 † 1	4/26 (15.38%)
Toothache † 1	1/26 (3.85%)
Vomiting † 1	3/26 (11.54%)
General disorders
Catheter site pain † 1	1/26 (3.85%)
Face oedema † 1	1/26 (3.85%)
Fatigue † 1	13/26 (50.00%)
Malaise † 1	5/26 (19.23%)
Medical device pain † 1	1/26 (3.85%)
Mucosal inflammation † 1	1/26 (3.85%)
Oedema peripheral † 1	9/26 (34.62%)
Pyrexia † 1	8/26 (30.77%)
Hepatobiliary disorders
Bile duct obstruction † 1	1/26 (3.85%)
Cholangitis † 1	3/26 (11.54%)
Hepatic function abnormal † 1	2/26 (7.69%)
Infections and infestations
Angular cheilitis † 1	1/26 (3.85%)
Bronchitis † 1	1/26 (3.85%)
Fungal infection † 1	1/26 (3.85%)
Gingivitis † 1	2/26 (7.69%)
Herpes zoster † 1	1/26 (3.85%)
Influenza † 1	1/26 (3.85%)
Liver abscess † 1	2/26 (7.69%)
Lung abscess † 1	1/26 (3.85%)
Nasopharyngitis † 1	2/26 (7.69%)
Pneumonia † 1	1/26 (3.85%)
Sepsis † 1	1/26 (3.85%)
Sinusitis † 1	1/26 (3.85%)
Investigations
Alanine aminotransferase increased † 1	1/26 (3.85%)
Amylase increased † 1	1/26 (3.85%)
Aspartate aminotransferase increased † 1	2/26 (7.69%)
Blood alkaline phosphatase increased † 1	2/26 (7.69%)
Blood bilirubin increased † 1	2/26 (7.69%)
Blood cholesterol increased † 1	2/26 (7.69%)
Blood creatine phosphokinase increased † 1	1/26 (3.85%)
Blood creatinine increased † 1	1/26 (3.85%)
Blood lactate dehydrogenase increased † 1	2/26 (7.69%)
Blood thyroid stimulating hormone increased † 1	1/26 (3.85%)
C-reactive protein increased † 1	1/26 (3.85%)
Thyroxine free increased † 1	1/26 (3.85%)
Tri-iodothyronine free increased † 1	1/26 (3.85%)
Weight decreased † 1	8/26 (30.77%)
Metabolism and nutrition disorders
Decreased appetite † 1	14/26 (53.85%)
Hypertriglyceridaemia † 1	1/26 (3.85%)
Hypoalbuminaemia † 1	3/26 (11.54%)
Hyponatraemia † 1	1/26 (3.85%)
Hypophosphataemia † 1	3/26 (11.54%)
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/26 (3.85%)
Back pain † 1	2/26 (7.69%)
Enthesopathy † 1	1/26 (3.85%)
Musculoskeletal pain † 1	1/26 (3.85%)
Musculoskeletal stiffness † 1	2/26 (7.69%)
Myalgia † 1	4/26 (15.38%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	4/26 (15.38%)
Tumour pain † 1	4/26 (15.38%)
Nervous system disorders
Akathisia † 1	1/26 (3.85%)
Dizziness † 1	1/26 (3.85%)
Dysgeusia † 1	1/26 (3.85%)
Headache † 1	4/26 (15.38%)
Muscle spasticity † 1	1/26 (3.85%)
Psychiatric disorders
Delirium † 1	3/26 (11.54%)
Depression † 1	1/26 (3.85%)
Insomnia † 1	1/26 (3.85%)
Renal and urinary disorders
Acute kidney injury † 1	1/26 (3.85%)
Haematuria † 1	1/26 (3.85%)
Proteinuria † 1	16/26 (61.54%)
Renal impairment † 1	2/26 (7.69%)
Urinary tract obstruction † 1	1/26 (3.85%)
Respiratory, thoracic and mediastinal disorders
Cough † 1	2/26 (7.69%)
Dysphonia † 1	16/26 (61.54%)
Dyspnoea † 1	1/26 (3.85%)
Epistaxis † 1	3/26 (11.54%)
Laryngeal pain † 1	2/26 (7.69%)
Oropharyngeal pain † 1	2/26 (7.69%)
Skin and subcutaneous tissue disorders
Alopecia † 1	3/26 (11.54%)
Dermatitis acneiform † 1	1/26 (3.85%)
Dermatitis contact † 1	1/26 (3.85%)
Eczema asteatotic † 1	1/26 (3.85%)
Nail discolouration † 1	1/26 (3.85%)
Palmar-plantar erythrodysaesthesia syndrome † 1	15/26 (57.69%)
Pruritus † 1	3/26 (11.54%)
Rash † 1	6/26 (23.08%)
Rash maculo-papular † 1	2/26 (7.69%)
Vascular disorders
Hypertension † 1	22/26 (84.62%)
Hypotension † 1	1/26 (3.85%)
Orthostatic hypotension † 1	1/26 (3.85%)
1 Term from vocabulary, MedDRA 21.1; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Inquiry Service.
• Organization: Eisai Co.,Ltd.
• EMail: eisai-chiken_hotline@hhc.eisai.co.jp

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Eisai Inc. ( Eisai Co., Ltd. )
• ClinicalTrials.gov Identifier: NCT02579616
• Other Study ID Numbers: E7080-J081-215
• First Submitted: October 16, 2015
• First Posted: October 19, 2015
• Results First Submitted: October 1, 2020
• Results First Posted: December 23, 2020
• Last Update Posted: December 23, 2020