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)

NCT03433703 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: E7080-M001-222
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Carcinoma, Hepatocellular

Keywords

Unresectable hepatocellular carcinoma; Lenvatinib; E7080

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From the first dose of study drug up to 28 days after the last dose of study drug (approximately 3 months)

Secondary Outcomes (3)

• Overall Survival (OS)

  From first dose date until date of death from any cause (approximately 3 months)

• Progression-free Survival (PFS)

  From first dose date until PD or date of death from any cause (approximately 3 months)

• Time to Progression (TTP)

  From first dose date until PD (approximately 3 months)

Study Arms (1)

Lenvatinib

EXPERIMENTAL

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, eligible participants will receive commercially available systemic TPC for hepatocellular carcinoma in the subsequent treatment period.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

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)

Also known as: LENVIMA®, E7080

Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Imaging findings for HCC corresponding to any of the following:
• HCC with ≥50% liver occupation
• Clear invasion into the bile duct
• 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

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (4)

California Liver Research Institute

Pasadena, California, 91105, United States

Location

University of Florida

Gainesville, Florida, 32611, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Limitations and Caveats

The study was terminated due to difficulty in enrolling the targeted number of participants. Secondary endpoints could not be analyzed because of very low sample size. No safety concerns involved in decision to stop enrollment.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 14, 2018
• Study Start: April 26, 2018
• Primary Completion: January 7, 2019
• Study Completion: January 7, 2019
• Last Updated: December 6, 2019
• Results First Posted: December 6, 2019

Record last verified: 2018-06

Locations

US (4)