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Trial to Evaluate Safety and Efficacy of Treatment of Physician Choice (TPC) Following First-Line Treatment of Lenvatinib in Subjects With Unresectable Hepatocellular Carcinoma (uHCC)

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ClinicalTrials.gov Identifier: NCT03433703
Recruitment Status : Recruiting
First Posted : February 14, 2018
Last Update Posted : August 21, 2018
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.

Brief Summary:
The primary objective of this study is to assess the safety and tolerability of subsequent treatment of physician's choice (TPC) following the first-line lenvatinib treatment in unresectable hepatocellular carcinoma (uHCC) participants.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Lenvatinib Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Multicenter, Phase 2 Trial to Evaluate Safety and Efficacy of Treatment of Physician Choice (TPC) Following First-Line Treatment of Lenvatinib in Subjects With Unresectable Hepatocellular Carcinoma (uHCC)
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : June 9, 2020
Estimated Study Completion Date : June 9, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Lenvatinib

Arm Intervention/treatment
Experimental: Lenvatinib
Participants will receive lenvatinib 12 or 8 milligrams (mg) once daily in continuous 28-day cycles until disease progression, development of unacceptable toxicity, participant request, withdrawal of consent, or study termination by the sponsor. Upon completion of lenvatinib treatment, participants may continue to receive commercially available treatment for hepatocellular carcinoma in the subsequent treatment period.
Drug: Lenvatinib

Lenvatinib capsules will be administered orally, once daily in continuous 28-day cycles.

Body weight (BW) ≥60 kilograms (kg) - Lenvatinib 12 mg (taken as three 4-mg capsules); BW <60 kg - Lenvatinib 8 mg (taken as two 4-mg capsules)

Other Names:
  • LENVIMA®
  • E7080




Primary Outcome Measures :
  1. Number of Participants with Treatment-emergent Adverse Events [ Time Frame: Up to 30 months ]
  2. Number of Participants with Treatment-emergent Serious Adverse Events [ Time Frame: Up to 30 months ]

Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 30 months ]
    OS will be measured from the date of the first dose of study treatment until the date of death from any cause.

  2. Progression-free Survival (PFS) [ Time Frame: Up to 30 months ]
    PFS is defined as the time from the date of the first dose of first-line lenvatinib treatment to the date of the first documentation of disease progression, or the date of death during the subsequent treatment of physician choice (TPC), whichever occurs first.

  3. Time to Progression (TTP) [ Time Frame: Up to 30 months ]
    TTP is defined as the time from the date of the first dose of first-line lenvatinib treatment to the date of the first documentation of disease progression during subsequent TPC.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Participants must have confirmed diagnosis of unresectable Hepatocellular Carcinoma (uHCC) with any of the following criteria:

    1. Histologically or cytologically confirmed diagnosis of HCC
    2. Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases criteria, including cirrhosis of any etiology or with chronic hepatitis B or C infection criteria
  • At least one measurable target lesion regardless if hepatic or non-hepatic according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) meeting the following criteria:

    1. Hepatic lesion

      • The lesion can be accurately measured in at least one dimension as ≥1.0 centimeters (cm) (viable tumor for typical; and longest diameter for atypical), and
      • The lesion is suitable for repeat measurement,
    2. Nonhepatic lesion

      • Lymph node lesion that measures at least one dimension as ≥1.5 cm in the short axis
      • Non-nodal lesion that measures ≥1.0 cm in the longest diameter Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
  • Participants categorized on the Barcelona Clinic Liver Cancer staging system to Stage B (not applicable for transarterial chemoembolization) or Stage C
  • Adequate bone marrow function, liver function, blood coagulation function, renal function, and pancreatic function as assessed by laboratory tests.
  • Adequately controlled blood pressure (BP) with up to 3 antihypertensive agents, defined as BP ≤150/90 millimeters of mercury (mmHg) at Screening and no change in antihypertensive therapy within 1 week prior to Cycle 1/Day 1
  • Child-Pugh A
  • Eastern Cooperative Oncology Group Performance Status of 0 or 1
  • Survival expectation of 12 weeks or longer before starting study drug

Key Exclusion Criteria:

  • Imaging findings for HCC corresponding to any of the following:

    1. HCC with ≥50% liver occupation
    2. Clear invasion into the bile duct
    3. Portal vein invasion at the main portal branch (Vp4)
  • Participants who have received any systemic chemotherapy, including sorafenib, regorafenib or other anti-vascular endothelial growth factor therapy, nivolumab, or any systemic investigational anticancer agents, including lenvatinib, for advanced/uHCC.
  • Participants 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) within 28 days prior to the first dose of lenvatinib study treatment.
  • Participants who have not recovered from toxicities as a result of prior anticancer therapy such as the local hepatic injection chemotherapy or any prior therapy for other cancer types.
  • Significant cardiovascular impairment within 6 months of the first dose of study drug
  • Prolongation of QT interval corrected for heart rate using Fridericia's correction (QTcF) to >480 milliseconds (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 international normalized ratio monitoring
  • Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least half teaspoon) within 28 days prior to the first dose of lenvatinib study treatment
  • 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
  • Any history of or current brain or subdural metastases
  • Participants having >1+ proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 grams/24 hour 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 participant's participation in a clinical study
  • Known intolerance to lenvatinib or any of the excipients
  • Human immunodeficiency virus positive or active infection requiring treatment (except for hepatitis virus)
  • Any history of drug or alcohol dependency or abuse within the prior 2 years
  • Major surgery within 3 weeks prior to the first dose of lenvatinib study treatment or scheduled for surgery during the study
  • Participant has had a liver transplant
  • Females who are breastfeeding or pregnant at Screening or Baseline
  • Females of childbearing potential who within 28 days before study entry did not use a highly effective method of contraception or do not agree to use a highly effective method of contraception throughout the entire study period

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03433703


Contacts
Contact: Eisai Medical Information, EJ 1-888-274-2378 esi_medinfo@eisai.com

Locations
United States, California
California Liver Research Institute Recruiting
Pasadena, California, United States, 91105
Contact: Edward, MD         
United States, Kentucky
University of Louisville Recruiting
Louisville, Kentucky, United States, 40202
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Sponsors and Collaborators
Eisai Inc.

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT03433703     History of Changes
Other Study ID Numbers: E7080-M001-222
First Posted: February 14, 2018    Key Record Dates
Last Update Posted: August 21, 2018
Last Verified: June 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Eisai Inc.:
Unresectable hepatocellular carcinoma
Lenvatinib
E7080

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
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action