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)
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Lenvatinib
Intervention description: 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)
Intervention MeSH terms: Lenvatinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Unresectable hepatocellular carcinoma; Lenvatinib; E7080

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

Eligibility 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 uHCC

               2. Clinically confirmed diagnosis of uHCC 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