A Multicenter, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Eisai Inc.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier:
NCT01761266
First received: January 2, 2013
Last updated: July 14, 2014
Last verified: July 2014
  Purpose

E7080-G000-304 is a multicenter, randomized, open-label, noninferiority Phase 3 study to compare the efficacy and safety of lenvatinib versus sorafenib as a first-line systemic treatment in subjects with unresectable Hepatocellular Carcinoma (HCC).


Condition Intervention Phase
Hepatocellular Carcinoma (HCC)
Drug: E7080
Drug: Nexavar
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Open-Label, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib (E7080) Versus Sorafenib in First-Line Treatment of Subjects With Unresectable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Overall survival (OS) [ Time Frame: Date of randomization to the date of disease progression (measured every 8 weeks) or death (whichever occurs first). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: Date of randomization to the date of disease progression (measured every 8 weeks) or death (whichever occurs first). ] [ Designated as safety issue: No ]

Estimated Enrollment: 940
Study Start Date: February 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Lenvatinib
Based on analysis from the Phase 1/2 study, lenvatinib is a promising treatment for advanced HCC patients. Therefore, this multicenter, randomized, open-label, Phase 3 trial is designed to compare the safety and efficacy of lenvatinib versus sorafenib in subjects with Child-Pugh A, unresectable/advanced HCC.
Drug: E7080
Lenvatinib: 12 mg (or 8 mg) once daily (QD) oral dosing
Active Comparator: Sorafenib
Sorafenib, an orally active multikinase inhibitor, will be used as a comparator. Sorafenib is approved in over 100 countries to date for the treatment of primary kidney cancer (advanced renal cell carcinoma) advanced primary liver cancer (HCC).
Drug: Nexavar
Sorafenib: 400 mg twice daily (BID) oral dosing

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Subjects must have confirmed diagnosis of unresectable HCC
  2. At least 1 measurable target lesion
  3. Subjects categorized to stage B (not applicable for transarterial chemoembolization [TACE]) stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
  4. Adequate bone marrow function
  5. Adequate liver function
  6. Adequate blood coagulation function

8. Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications 9. Child-Pugh score A 10. ECOG-PS 0 or 1 11. Survival expectation of 12 weeks or longer after starting study drug 12. Males or females aged at least 18 years (or any age greater than 18 years as determined by country legislation) at the time of informed consent

Exclusion Criteria

  1. Imaging findings for HCC corresponding to any of the following:

    • HCC with greater than or equal to 50% liver occupation
    • Clear invasion into the bile duct
    • Portal vein invasion at the main portal branch (Vp4)
  2. 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.
  3. 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
  4. Gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib in the opinion of the investigator
  5. 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.)
  6. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to randomization
  7. Gastric or esophageal varices that require treatment
  8. Meningeal carcinomatosis
  9. Subjects having >1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria. Subjects with urine protein greater than or equal to 1 g/24 h will be ineligible.
  10. Arterial-portal venous shunt or arterial-venous shunt preventing proper diagnosis of tumor
  11. Any medical or other condition that in the opinion of the investigator would preclude the subject's participation in a clinical study
  12. Any history of drug or alcohol dependency or abuse within the prior 2 years
  13. Major surgery within 3 weeks prior to randomization or scheduled for surgery during the study
  14. Subject has had a liver transplant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01761266

Contacts
Contact: Eisai Eisai Medical Services 1-888-4224743

  Show 137 Study Locations
Sponsors and Collaborators
Eisai Limited
Investigators
Study Director: Mark M Jones Eisai Inc.
  More Information

No publications provided

Responsible Party: Eisai Inc. ( Eisai Limited )
ClinicalTrials.gov Identifier: NCT01761266     History of Changes
Other Study ID Numbers: E7080-G000-304
Study First Received: January 2, 2013
Last Updated: July 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014