UMIN-CTR Clinical Trial

Public title

Observational Study of Lenvatinib Pharmacokinetics and Treatment Efficacy in patients with Hepatocellular Carcinoma

Acronym

HCC-Len-PK

Scientific Title

A Prospective Observational Study on the Association between Pharmacokinetics, Genetic Polymorphisms, Soluble MICA Levels and Treatment Outcomes of Lenvatinib in Patients with Unresectable Advanced or Recurrent Hepatocellular Carcinoma

Scientific Title:Acronym

LENPK-MICA-HCC

Region

Japan

Condition

Unresectable Advanced or Recurrent Hepatocellular Carcinoma

Classification by specialty

Hepato-biliary-pancreatic medicine

Classification by malignancy

Malignancy

Genomic information

YES

Narrative objectives1

To identify factors associated with efficacy and toxicity of lenvatinib in Japanese patients with hepatocellular carcinoma through the analysis of pharmacokinetics, genetic polymorphismss, and soluble MICA concentrations. This study aims to contribute to improving treatment outcome prediction, adverse event management, and the advancement of personalized medicine in lenvatinib therapy.

Basic objectives2

Pharmacokinetics

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Primary outcomes

Correlation between lenvatinib pharmacokinetic parameters (AUC, Cmax, T1/2) measured at specified time points (pre-dose, 0.5, 1, 2, 4, 8, 24, 48 hours post-dose, and day 15+/-2) with objective response rate (ORR) at 12 weeks and progression-free survival (PFS) based on RECIST v1.1 criteria

Key secondary outcomes

1. Association between profiles of genetic polymorphisms identified by exome analysis of pre-treatment tumor tissue or blood samples with treatment response according to RECIST v1.1 criteria at 24 weeks and adverse events (evaluated by CTCAE v5.0)
2. Correlation between temporal changes in soluble MICA concentrations (measured pre-treatment, day 15 +/- 2, and every 4 weeks thereafter) and best overall response determined by imaging assessment
3. Relationship between lenvatinib pharmacokinetic parameters (AUC, Cmax) and incidence of Grade 2 or higher adverse events according to CTCAE v5.0 within 24 weeks of treatment initiation
4. Correlation between overall survival (OS) from treatment initiation to the end of follow-up period (maximum 24 months) and pharmacokinetic parameters

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<

Age-upper limit

100

years-old

>=

Gender

Male and Female

Key inclusion criteria

1. Patients with histologically confirmed hepatocellular carcinoma or non-invasively diagnosed according to American Association for the Study of Liver Diseases (AASLD) criteria
2. Patients with unresectable advanced or recurrent disease
3. Patients aged 20 years or older at the time of treatment initiation
4. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
5. Patients with measurable or evaluable lesions
6. Patients with an expected survival of at least 3 months
7. Patients with adequate bone marrow and organ function as assessed by blood tests conducted within 7 days prior to treatment initiation
8. Patients who have provided written informed consent with signature and date prior to enrollment in this study

Key exclusion criteria

1. Patients with severe hepatic dysfunction (Child-Pugh score 10-15)
2. Patients with severe active infection
3. Patients with active double primary cancer
4. Patients deemed difficult to participate in the study due to psychiatric or neurological disorders
5. Pregnant or breastfeeding women, women who may become (or intend to become) pregnant, or men who wish to father children
6. Patients with a history of serious drug hypersensitivity or drug allergy
7. Patients taking medications that affect CYP3A4 (such as phenytoin, carbamazepine, rifampicin, phenobarbital, ketoconazole, macrolide antibiotics, etc.) (eligible if discontinued at least 1 week prior to treatment)
8. Patients with contraindications to lenvatinib
9. Patients judged by the attending physician to be inappropriate for safe conduct of this study

Target sample size

50

Name of lead principal investigator

1st name	Yuki
Middle name
Last name	Ichikawa

Organization

Showa University School of Medicine

Division name

Division of Gastroenterology, Department of Medicine

Zip code

142-8555

Address

1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

TEL

03-3784-8000

Email

yamadayuki@med.showa-u.ac.jp

Name of contact person

1st name	Yuki
Middle name
Last name	Ichikawa

Organization

Division of Gastroenterology, Department of Medicine

Division name

Division of Gastroenterology, Department of Medicine

Zip code

142-8555

Address

1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

TEL

03-3784-8000

Homepage URL

Email

yamadayuki@med.showa-u.ac.jp

Institute

Showa University

Institute

Department

Personal name

Organization

Ministry of Education, Culture, Sports, Science and Technology

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Division of Cancer Genome and Pharmacotherapy, Department of Clinical Pharmacy, Showa University School of Pharmacy
Laboratory of Molecular Pharmacotherapeutics, Faculty of Pharmacy, Kanazawa University

Name of secondary funder(s)

Organization

Clinical Research Support Division, Integrated Research Promotion Center, Showa University

Address

1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan

Tel

03-3784-8305

Email

m-rinri@ofc.showa-u.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2025

Year

02

Month

27

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2020

Year

03

Month

03

Day

Date of IRB

2020

Year

04

Month

16

Day

Anticipated trial start date

2020

Year

04

Month

16

Day

Last follow-up date

2026

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

This study is a non-interventional prospective observational study. It aims to analyze the pharmacokinetics of lenvatinib before and after administration in hepatocellular carcinoma patients to examine the relationship between systemic disposition and drug response. Additionally, it will analyze the relationship between blood concentration of anti-tumor immune ligand MICA (MHC class I polypeptide-related sequence A) and treatment efficacy. Blood samples will be collected before administration, 0.5, 1, 2, 4, 8, 24, and 48 hours after administration, and on day 15, with urine samples collected before administration. Genetic mutation analysis will also be performed. The study targets patients with unresectable advanced or recurrent hepatocellular carcinoma and will be conducted as a multi-center collaborative study led by Showa University.

Registered date

2025

Year

02

Month

26

Day

Last modified on

2025

Year

02

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000065301