A phase 3 trial studying how well lenvatinib works in treating patients with liver cancer who would not benefit from surgery compared against sorafenib. The trial is taking place worldwide, patients and their physician will know if they are receiving lenvatinib or sorafenib

Phase 1

• Conditions: nresectable Hepatocellular Carcinoma; MedDRA version: 16.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-002992-33-ES
• Lead Sponsor: Eisai Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-07-12
• Last Update Posted: 23 October 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 954

Inclusion Criteria

- Confirmed diagnosis of unresectable HCC with any of the following criteria: histologically or cytologically confirmed diagnosis of HCC, diagnosis of HCC according to the AASLD criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteria
- At least 1 measurable target lesion according to mRECIST meeting the criteria set out in the protocol for the different lesions
-Subjects categorized to stage B or stage c based on BCLC staging system
- Adequate bone marrow function defined as
oAbsolute neutrophil count (ANC) ? 1.5 × 10e9/L
oHemoglobin (Hb) ? 8.5 g/dL
oPlatelet count ? 75 × 10e9/L

- Adequate liver function
oAlbumin ? 2.8 g/dL
oBilirubin ? 3.0 mg/dL
oAspartate 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 > 30 mL/min calculated per the Cockcroft and Gault formula
- Adequate pancreatic function, defined as amylase and lipase ? 1.5 × ULN
- Adequately controlled blood pressure with 0 or 1 antihypertensive medications and no change in antihypertensive medications within 1 week prior to the cycle 1/ day 1
- Child-pugh score A
- ECOG-PS 0 or 1
- Survival expectation of 12 weeks or longer after starting study drug
- Males or females aged at least 18 years at time of informed consent
- Females must not be lactating or pregnant at Screening or Baseline. A seperate baseline assessment is required if a negative pregnancy test was obtained more then 72 hours before the first dose of study drug.
- All females will be considered to be of childbearing potential unless they are postmenopausal or have been sterilized surgically.
- Females of childbearing potential must not have had unprotected sexual intercourse within 30 days before study entry and must agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method, a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period and for 30 days after study drug discontinuation. If currently abstinent, the subject must agree to use a double barrier method as described above if she becomes sexually active during the study period or for 30 days after study drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and must continue to use the same contraceptive during the study and for 30 days after study drug discontinuation.
- Male subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must meet the criteria above. No sperm donation is allowed during the study period and for 30 days after study drug administration
- Provide written informed consent
- Willing and able to comply with all aspects of the protocol
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 610
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 330

Exclusion Criteria

- Imaging findings for HCC corresponding to any of the following: HCC with greater or equal 50% liver occupation, clear invasion of the bile duct, portal vein invasion at the main portal branch
- Subjects who have received any systemic chemotherapy, including sorafenib, or any systemic investigational anticancer agents, including lenvatinib, for advanced/unresectable HCC. Note: Subjects who have received local hepatic injection chemotherapy are eligible.
- Subjects who have received any anticancer therapy (including surgery, percutaneous ethanol injection, radio frequency ablation, transarterial [chemo] embolization, hepatic intra-arterial chemotherapy, biological, immunotherapy, hormonal, or radiotherapy) or any blood enhancing treatment (including blood transfusion, blood products, or agents that stimulate blood cell production, e.g., granulocyte colony-stimulating factor [G-CSF])
within 28 days prior to randomization
- Subjects 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 QTc interval to > 480 ms
- Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the investigator
- Bleeding or thrombotic disorders or use of anticoagulants such as, warfarin or similar agents requiring therapeutic INR monitoring. (Treatment with low molecular weight heparin is allowed.)
- Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization
- Gastric or esophageal varices that require treatment
- 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
- Meningeal carcinomatosis
- Any history of, or current, brain or subdural metastases
- Subjects having > 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein ? 1 g / 24 h will be ineligible
- Arterial-portal venous shunt or arterial-venous shunt preventing proper diagnosis of tumor
- Any medical or other condition that in the opinion of the investigator would preclude the subject?s participation in a clinical study
- Known intolerance to lenvatinib or sorafenib (or any of the excipients)
- Human immunodeficiency virus (HIV) positive or active infection requiring treatment (except for hepatitis virus)
- Any history of drug or alcohol dependency or abuse within the prior 2 years
- Any subject who cannot be evaluated by either triphasic liver CT or triphasic liver MRI because of allergy or other contraindication to both CT and MRI contrast agents
- Major surgery within 3 weeks prior to randomization or scheduled for surgery during the study
- Subject has had a liver transplant

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified