Clinical trial NCT03009292: Pharmacokinetic Study of E7080/Lenvatinib in Chinese Subjects With Solid Tumor
Official title: Pharmacokinetic Study of E7080/Lenvatinib in Chinese Subjects With Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumor
Keywords: solid tumor
Lenvatinib
pharmacokinetics
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2017-01-04
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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
* Males and females of childbearing potential must agree to use appropriate contraception from the giving of consent to 30 days after study drug administration. Female participants of childbearing potential must test negative for pregnancy at screening
* Participants who voluntarily agree to participate in this study in writing

Exclusion Criteria:

* Participants with brain metastasis accompanied by clinical symptoms or requiring treatment
* Participants with the following complications or medical history

  1. Systemic severe infections requiring medical treatment
  2. The following cardiovascular diseases

     1. Ischemic cardiac disease or arrhythmia requiring medical treatment
     2. Angina pectoris or myocardial infarction within 24 weeks before enrollment
     3. Corrected QT interval (QTc) greater than 480 milliseconds (msec) (Fridericia's method)
  3. Hemoptysis (fresh blood) ≥ 1/2 teaspoon (2.5 mL) or clinically significant hemorrhagic or thrombotic events within 4 weeks before enrollment
  4. Systolic pressure ≥150 millimeters of mercury (mmHg) and diastolic pressure ≥90 mmHg
  5. If proteinuria is ≥2+ in a qualitative test for urine protein, ≥1.0 grams for 24 hours is accumulated
  6. Complications or surgery (such as malabsorption syndrome, chronic diarrhea, or total gastrectomy) that could significantly influence the absorption of the investigational drug
  7. Have undergone major surgery within 4 weeks before enrollment
  8. Co-existing effusion requiring treatment
* Participants unable to take oral medication
* Participants scheduled for surgery during the projected course of the study
* Participants who test positive for human immunodeficiency virus (HIV antibody), or positive for hepatitis B surface (HBs antigen) or hepatitis C virus (HCV antibody)
* Participants who have taken lenvatinib before
* Participants who in the view of the principal investigator or sub-investigator are not able to comply with this protocol because of psychiatric or physical diseases including alcoholism or drug addiction
* Pregnant or nursing participants
* Participants who are participating in another clinical trial

Primary outcomes:
measure: Area under the concentration-time curve over the dosing interval on multiple dosing (AUC[0-τ])
timeFrame: 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)
measure: Time at which the highest drug concentration occurs at steady-state (tss,max)
timeFrame: 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)
measure: Average steady-state concentration (Css,av)
timeFrame: 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)
measure: Minimum observed concentration at steady-state (Css,min)
timeFrame: 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
measure: Maximum observed concentration at steady-state (Css,max)
timeFrame: 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)
measure: Area under the concentration-time curve from zero time to time of last quantifiable concentration (AUC[0-t])
timeFrame: 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)
measure: Time at which the highest drug concentration occurs (tmax)
timeFrame: 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)
measure: Maximum observed concentration (Cmax)
timeFrame: 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:
measure: Mean blood urea nitrogen (BUN) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean creatinine values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean albumin values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean cholesterol values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean lactate dehydrogenase values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean total protein values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean C-reactive protein (CRP) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean gamma-glutamyl transpeptidase (γ-GTP) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean total bilirubin values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean alanine transaminase (ALT) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean aspartate transaminase (AST) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean alkaline phosphatase (ALP) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean body temperature
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean body weight
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean heart rate
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean QT values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean QT corrected (QTc) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean QTc corrected using Fridericia's method (QTcF) values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Number of participants with abnormal, clinically significant physical examination findings
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean calcium values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean chloride values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean potassium values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean sodium values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean lymphocyte count
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean neutrophil count
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean white blood cell (WBC) count
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean platelet count
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean hemoglobin values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean red blood cell (RBC) count
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Number of participants with any serious adverse event and any non-serious adverse event
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean protein in urine values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean glucose in urine values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean occult blood in urine values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean systolic blood pressure and diastolic blood pressure values
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
measure: Mean pulse
timeFrame: until disease progression, development of unacceptable toxicity, participant requests to discontinue, or withdrawal of consent (up to Day 28)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
Study officials:
affiliation: Eisai Inc.
name: Eisai Medical Information
role: STUDY_DIRECTOR
References:
citation: 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.