Pharmacokinetic Study of E7080/Lenvatinib in Chinese Patients With Unresectable Hepatocellular Carcinoma (HCC)

NCT02953743 | Completed Phase 1

• 1 other identifier: E7080-C086-107
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

The primary purpose of this study is to assess the single- and multiple-dose pharmacokinetic (PK) profile of lenvatinib in Chinese participants with unresectable Hepatocellular Carcinoma (HCC).

Conditions

Unresectable Hepatocellular Carcinoma (HCC)

Keywords

E7080; Lenvatinib; Pharmacokinetic study; Chinese participants; Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (8)

• Mean maximum observed concentration (Cmax)

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Mean time at which the highest drug concentration occurs (tmax)

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Mean area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC(0-t))

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Mean maximum observed concentration at steady-state (Css,max )

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Mean minimum observed concentration at steady-state (Css,min)

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Average steady-state concentration (Css,av)

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Mean time at which the highest drug concentration occurs at steady-state (tss,max)

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

• Mean area under the concentration-time curve over the dosing interval on multiple dosing (AUC(0-τ))

  Day 1 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 2 at pre-dose; Day 8 at pre-dose; Day 15 at pre-dose, 0.5, 1, 2, 4, 6, and 8 hours; Day 16 at pre-dose; and Day 22 at pre-dose

Secondary Outcomes (1)

• Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs)

  Up to 30 days after the administration of the last dose of study drug or up to approximately 1 year

Study Arms (2)

Lenvatinib 12 mg

EXPERIMENTAL

Participants weighing ≥ 60 kg will be enrolled in this arm.

Drug: Lenvatinib

Lenvatinib 8 mg

EXPERIMENTAL

Participants weighing \< 60 kg will be enrolled in this arm.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib 4 mg capsules will be administered orally, once daily continuously 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.

Lenvatinib 12 mg; Lenvatinib 8 mg

Eligibility Criteria

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

You may qualify if:

• Participants must have confirmed diagnosis of unresectable Hepatocellular Carcinoma (HCC) with any of the following criteria:
• Histologically or cytologically confirmed diagnosis of HCC
• Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteria
• Participants categorized to stage B (not applicable for transarterial chemoembolization \[TACE\]) or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
• Adequate bone marrow function, defined as:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/Liter (L)
• Hemoglobin (Hb) ≥ 8.5 gram per deciliter (g/dL)
• Platelet count ≥ 75 × 10\^9/L
• Adequate liver function, defined as:
• Albumin ≥ 2.8 g/dL
• Bilirubin ≤ 3.0 milligram per deciliter (mg/dL)
• Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) ≤ 5 × the upper limit of normal (ULN)
• Adequate blood coagulation function, defined as international normalized ratio (INR) ≤ 2.3
• Adequate renal function defined as creatinine clearance \> 40 milliliter per min (mL/min) calculated per the Cockcroft-Gault formula
• Adequately controlled blood pressure (BP) with up to 3 antihypertensive agents, defined as systolic BP ≤ 150 millimeter of mercury (mm Hg) and diastolic BP ≤ 90 mm Hg at screening and no change in antihypertensive therapy within 1 week prior to the registration.

You may not qualify if:

• Imaging findings for HCC corresponding to any of the following:
• HCC with ≥50% liver occupation
• Clear invasion into the bile duct
• Portal vein invasion at the main portal branch (Vp4)
• Participants who have received lenvatinib
• Participants who have received any anti-cancer therapy (including surgery, percutaneous ethanol injection, radio frequency ablation, transarterial \[chemo\] embolization, hepatic intra-arterial chemotherapy, biological, immunotherapy, hormonal, any investigational drugs or radiotherapy) or any blood enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production, eg, granulocyte colony-stimulating factor \[G-CSF\]) within 28 days prior to registration.
• Participants who have not recovered from toxicities as a result of prior anticancer therapy except alopecia and infertility. Recovery is defined as \< Grade 2 severity per Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening
• Prolongation of Q wave and T wave interval corrected by the Fridericia formula (QTcF) interval to \> 480 milli second (msec)
• Gastrointestinal malabsorption, or any other condition in the opinion of the investigator that might affect the absorption of lenvatinib
• Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin and factor X inhibitors which do not require INR monitoring is permitted. Antiplatelet agents are prohibited throughout the study.
• Gastrointestinal bleeding event within 28 days prior to registration
• Gastric or esophageal varices that require interventional treatment within 28 days prior to randomization. Prophylaxis with pharmacologic therapy (eg, nonselective beta-blocker) is permitted.
• Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to registration
• Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months from registration.

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (3)

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Location

Shanghai Cancer Hospital, Fudan University

Shanghai, Shanghai Municipality, China

Location

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Location

Related Publications (1)

• Bai Y, Hu X, Ren Z, Hisai T, Yusa W, Weng L, Shiba S, Takase T. A phase I pharmacokinetic study of lenvatinib in Chinese patients with unresectable hepatocellular carcinoma. Future Oncol. 2022 Jul;18(22):2413-2424. doi: 10.2217/fon-2022-0229. Epub 2022 Jun 8.

  PMID: 35674480 DERIVED

MeSH Terms

Interventions

lenvatinib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2016
• First Posted: November 3, 2016
• Study Start: September 1, 2016
• Primary Completion: June 28, 2017
• Study Completion: December 28, 2020
• Last Updated: April 1, 2021

Record last verified: 2021-02

Locations

CN (3)