Pharmacokinetic Study of E7080/Lenvatinib in Chinese Subjects With Solid Tumor

NCT03009292 | Completed Phase 1

• 1 other identifier: E7080-C086-108
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

Study E7080-C086-108 is an open-label, single- and multiple-dose pharmacokinetic (PK) study of lenvatinib (administered orally, once a day \[QD\]) in Chinese participants with solid tumor. A total of 12 participants will be enrolled to evaluate the PK of 24 milligrams (mg) QD dosing of lenvatinib.

Conditions

Solid Tumor

Keywords

solid tumor; Lenvatinib; pharmacokinetics

Outcome Measures

Primary Outcomes (8)

• Area under the concentration-time curve over the dosing interval on multiple dosing (AUC[0-τ])

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. AUC(0-τ) is defined as the area under the concentration-time profile from time zero to the end of the dosing interval at steady state. AUC represents the total drug exposure over a defined period of time.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

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

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. tss,max is the time at which the maximum concentration of lenvatinib is observed in the plasma at steady state, which occurs when the rates of drug administration and drug elimination are equal.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

• Average steady-state concentration (Css,av)

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,av is the average concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when the rates of drug administration and drug elimination are equal.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

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

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,min is the lowest concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when the rates of drug administration and drug elimination are equal.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15

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

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Css,max is the highest concentration of lenvatinib in plasma at the time that a steady state has been achieved, which occurs when rates of drug administration and drug elimination are equal.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

• Area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t])

  Blood samples will be collected to determine the plasma lenvatinib concentration at various time points. AUC(0-t) is defined as the AUC from time "0" to the time of the last measurable concentration. AUC represents the total drug exposure over a defined period of time.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

• Time at which the highest drug concentration occurs (tmax)

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Tmax is the time at which the maximum concentration of lenvatinib is observed in plasma after a single dose of lenvatinib.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

• Maximum observed concentration (Cmax)

  Blood samples will be collected to determine the plasma lenvatinib concentration at the specified time points. Cmax is the highest concentration of lenvatinib observed in plasma after a single dose of lenvatinib.

  Day 1: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 2: pre-dose (24 hours after first administration). Day 8: pre-dose. Day 15: pre-dose; 1, 2, 4, and 8 hours post-dose. Day 16: pre-dose (24 hours after administration on Day 15)

Secondary Outcomes (35)

• Mean blood urea nitrogen (BUN) values

  until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)

• Mean creatinine values

  until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)

• Mean albumin values

  until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)

• Mean cholesterol values

  until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)

• Mean lactate dehydrogenase values

  until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)

Study Arms (1)

24 mg lenvatinib

EXPERIMENTAL

Participants will receive once daily oral dosing of lenvatinib 24 milligrams (mg)

Drug: lenvatinib

Interventions

lenvatinib DRUG

once daily continuous dosing

24 mg lenvatinib

Eligibility Criteria

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

You may qualify if:

• Participants with a histological and/or cytological diagnosis of solid tumor
• Participants with solid tumor that is resistant to standard anti-tumor therapies, or for which no appropriate treatment is available
• Participants whose toxicity of previous treatment has recovered to Grade 1 or lower (except for alopecia)
• Participants who have completed previous anti-tumor therapy (such as surgery, radiotherapy) at least 4 weeks before treatment
• Participants who are 18 years or older at the time of obtaining informed consent
• Participants with an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
• Participants who meet all of the following items:
• Hemoglobin ≥9.0 grams per deciliter (g/dL)
• Neutrophil count ≥1.5×10\^3/microliters (µL)
• Platelet count ≥10×10\^4/µL
• Total bilirubin ≤1.8 milligrams (mg)/dL
• Aspartate aminotransferase (AST) ≤100 International Units per liter (IU/L)
• Alanine aminotransferase (ALT) ≤100 IU/L
• Serum creatinine ≤1.5 mg/dL or creatinine clearance ≥50 milliliters per minute (mL/min). Creatinine clearance will be calculated based on Cockcroft-Gault method using the following formula: Male: (140-age) × weight ÷ (serum creatinine × 72); Female: 0.85 × (140-age) × weight ÷ (serum creatinine × 72).
• Participants expected to survive for 12 weeks or longer

You may not qualify if:

• Participants with brain metastasis accompanied by clinical symptoms or requiring treatment
• Participants with the following complications or medical history
• Systemic severe infections requiring medical treatment
• The following cardiovascular diseases
• Ischemic cardiac disease or arrhythmia requiring medical treatment
• Angina pectoris or myocardial infarction within 24 weeks before enrollment
• Corrected QT interval (QTc) greater than 480 milliseconds (msec) (Fridericia's method)
• Hemoptysis (fresh blood) ≥ 1/2 teaspoon (2.5 mL) or clinically significant hemorrhagic or thrombotic events within 4 weeks before enrollment
• Systolic pressure ≥150 millimeters of mercury (mmHg) and diastolic pressure ≥90 mmHg
• If proteinuria is ≥2+ in a qualitative test for urine protein, ≥1.0 grams for 24 hours is accumulated
• Complications or surgery (such as malabsorption syndrome, chronic diarrhea, or total gastrectomy) that could significantly influence the absorption of the investigational drug
• Have undergone major surgery within 4 weeks before enrollment
• Co-existing effusion requiring treatment
• Participants unable to take oral medication
• Participants scheduled for surgery during the projected course of the study

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (2)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Location

Related Publications (1)

• Liu D, Liu L, Shen L, Kubota T, Suzuki T, Ikezawa H, Shiba S, Bai Y. Pharmacokinetic study of lenvatinib in Chinese patients with solid tumors. Future Oncol. 2021 May;17(15):1855-1863. doi: 10.2217/fon-2020-0877. Epub 2021 Jan 21.

  PMID: 33474967 DERIVED

MeSH Terms

Interventions

lenvatinib

Study Officials

• Eisai Medical Information

  Eisai Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2016
• First Posted: January 4, 2017
• Study Start: August 6, 2018
• Primary Completion: December 24, 2018
• Study Completion: August 27, 2021
• Last Updated: September 28, 2021

Record last verified: 2021-03

Locations

CN (2)