A Study to Assess the Safety and Efficacy of Lenvatinib as First-line Treatment in Participants With Unresectable HCC

NCT04297254 | Completed Phase 4

• 1 other identifier: E7080-M091-511
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

Brief Summary

The primary objective of this study is to evaluate the safety of lenvatinib in HCC.

Conditions

Carcinoma, Hepatocellular

Keywords

Lenvatinib; E7080; Unresectable hepatocellular carcinoma

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)

  TEAEs are defined as undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment. The severity of all adverse events (AEs) will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The grades are: Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily life \[ADL\]); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (Life-threatening consequences; urgent intervention indicated); and Grade 5 (Death related to AE).

  Baseline up to Week 24

• Number of Participants with Serious Adverse Events (SAEs)

  Baseline up to Week 24

• Number of Participants with Grades 1 and 2 Treatment-emergent Adverse Events (TEAEs)

  TEAEs are defined as undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the treatment. The severity of all AEs will be graded according to CTCAE version 4.0. The grades are: Grade 1 (Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated); Grade 2 (Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL); Grade 3 (Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL); Grade 4 (Life-threatening consequences; urgent intervention indicated); and Grade 5 (Death related to AE).

  Baseline up to Week 24

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  From the start of study treatment up to Week 24

• Progression-free Survival (PFS)

  From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurs first) or up to approximately Week 24

• Percentage of Participants Requiring Dose Modifications (Dose Interruptions or Dose Reductions)

  Baseline up to Week 24

• Time to First Dose Reduction

  Baseline up to Week 24

Study Arms (1)

Lenvatinib 12 mg or 8 mg

EXPERIMENTAL

Participants with body weight (BW) greater than or equal to (\>=) 60 kilogram (kg), will receive lenvatinib 12 milligram (mg) (03 capsules), and participants with BW less than (\<) 60 kg, will receive lenvatinib 8 mg, (02 capsules), orally, once daily with or without food in 28-day cycles for a maximum 6 cycles of 4 weeks each for a total of 24 weeks or until disease progression, death, intolerable or unacceptable toxicity, or withdrawal of consent, whichever occurs earlier.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Lenvatinib capsules.

Lenvatinib 12 mg or 8 mg

Eligibility Criteria

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

You may qualify if:

• Males or females of \>=18 years of age
• Participant or their legally acceptable representative (LAR) is willing to sign written informed consent for participation in the study and ready to comply with the study procedures and schedule
• Must have a confirmed diagnosis of unresectable HCC with one of the following criteria:
• Histologically or cytologically confirmed diagnosis of HCC
• Clinically confirmed diagnosis of HCC according to the American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any aetiology or with chronic hepatitis B or C infection criteria
• At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:
• Hepatic lesion:
• The lesion can be accurately measured in at least one dimension as \>=1.0 centimeter (cm)
• The lesion is suitable for repeat measurement
• Non-hepatic lesion:
• Lymph node (LN) lesion that measures at least one dimension as \>=1.5 cm in the short axis, except for porta hepatis LN that measures \>=2.0 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 are categorized to Stage B (not applicable for transarterial chemoembolization \[TACE\]) or Stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
• Has adequate bone marrow function, defined as:

You may not qualify if:

• With 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)
• Who have received any systemic chemotherapy, including sorafenib, or immunotherapy, or any systemic investigational anticancer agents for advanced/unresectable HCC
• 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, example granulocyte colony-stimulating factor \[G-CSF\]) within 28 days prior to enrolment
• Who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility
• With significant cardiovascular impairment including but not limited to the history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within previous 6 months, or cardiac arrhythmia requiring medical treatment at the time of screening
• With prolongation of corrected QT (QTc) interval to \>480 millisecond (ms)
• With 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 (INR) monitoring
• Having a gastrointestinal bleeding event or active haemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to enrollment
• With gastric or oesophageal varices that may require treatment
• With any other 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 prior to enrolment
• Any history of, or concurrent, brain or subdural metastases

Sponsors & Collaborators

• Eisai Pharmaceuticals India Pvt. Ltd: lead

Study Sites (10)

HCG Comprehensive Cancer Care Hospital

Bangalore, Karnataka, 560027, India

Location

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

Location

HCG Manavata Cancer Centre

Nashik, Maharashtra, 422002, India

Location

Shatabdi Hospital

Nashik, Maharashtra, 422005, India

Location

Apex Wellness Hospital

Nashik, Maharashtra, 422009, India

Location

LMMF's Deenanath Mangeshkar Hospital & Research Center

Pune, Maharashtra, 411004, India

Location

Noble Hospital

Pune, Maharashtra, 411013, India

Location

Somani Hospital

Jaipur, Rajasthan, 302019, India

Location

Meenakshi Mission Hospital

Madurai, Tamil Nadu, 625107, India

Location

Apollo Gleneagles Hospital Limited

Kolkata, West Bengal, 700054, India

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2020
• First Posted: March 5, 2020
• Study Start: February 4, 2021
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: November 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share

Locations

IN (10)