Study in use of Lenvatinib in patients with unable to be removed by surgery Hepatocellular Carcinoma

Phase 4

Recruiting

• Conditions: Neoplasms,

• Registration Number: CTRI/2020/08/027136
• Lead Sponsor: Eisai Pharmaceuticals India Pvt Ltd

Brief Summary

This is a prospective, multicenter, open-label, single-arm, non-comparative, post-marketing phase IV study. A total of 50 patients with unresectable hepatocellular carcinoma (HCC) will be enrolled across 10 centers in India. All the patients will receive Lenvatinib orally, once daily for a maximum of 6 treatment cycles of 4 weeks each for up to 24 weeks or until disease progression or death, intolerable or unacceptable toxicity, or withdrawal of consent, whichever occurs earlier.

Safety will be monitored by capturing all the adverse events from the start of Lenvatinib treatment until 24 weeks or last study visit, whichever occurs earlier. Efficacy assessment will be done via CT or MRI Scan, prior to the enrolment and every 8 weeks thereafter till the end of the study treatment. Continuation of the patient’s participation in the study will be determined based on the radiological responses by the Investigator. Discontinuation of treatment will be based on radiological evaluation or Investigator’s discretion (on clinical judgment) if there is no benefit for the patient in receiving further study treatment.

Patients will be assessed for the study objectives only for the study treatment period i.e. till week 24 or less in case of disease progression/death/unacceptable toxicity/consent withdrawal.

End of treatment: The end of treatment for a patient will be the end of 24 weeks from the start of Lenvatinib or last study treatment visit, if earlier.

Continuation of Treatment after 24 weeks:

Post 24 weeks of therapy, patients who continue to show clinical/radiological benefit will be able to continue to receive Lenvatinib (beyond week 24, as necessary) as per Investigator’s discretion and based on radiological response. In patients receiving Lenvatinib after 24 weeks, adverse events will be monitored by the Investigator, and will not be part of the formal study report. Tumor assessment will also be continued every 8 weeks in order to ascertain continuing clinical/radiological benefit in these patients, and further decision to continue or stop the treatment will be taken by Investigator and/or treating physician.

End of Study:All patients will be followed up at 4 weeks after the completion of 24 weeks of treatment, or after last treatment visit if earlier, as applicable. This will be the end-of- study visit

Detailed Description

Not available

Study Timeline

• Study Start: 2020-09-30
• Last Update Posted: 2022-07-25

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Males or females of ≥ 18 years of age.
• Patient 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.
• Patient must have a confirmed diagnosis of unresectable hepatocellular carcinoma (HCC) with one of the following criteria: a)Histologically or cytologically confirmed diagnosis of HCC.
• b) 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: a.
• Hepatic lesion:The lesion can be accurately measured in at least one dimension as ≥ 1.0 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.
• Patient is categorized to stage B (not applicable for TACE) or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
• Patient has adequate bone marrow function, defined as: a)Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
• b) Haemoglobin ≥ 8.5 g/dL.
• c)Platelet count ≥ 75 × 109/L.
• Adequate liver function based on liver function tests, defined as: a) Albumin ≥ 2.8 g/dL.
• b) Bilirubin ≤ 3.0 mg/dL.
• c) Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) ≤ 5 × the upper limit of normal (ULN).
• Adequate renal function, defined as > 30 ml/min calculated as per the Cockcroft and Gault formula#.
• Adequately controlled blood pressure (BP) with 0 or 1 antihypertensive medications, defined as BP ≤ 150/90 mm Hg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
• Adequate pancreatic function, defined as amylase and lipase ≤ 1.5 × ULN.
• Patient with a Child-Pugh score A.
• Patient with Eastern Cooperative Oncology Group (ECOG) performance status of 0–1.
• Patient with life expectancy of ≥ 12 weeks from the start of study treatment, as per Investigator’s judgement.

Exclusion Criteria

• Patients who meet any of the following criteria will be excluded from this study.
• Patients with imaging findings for HCC corresponding to any of the following: a) HCC with ≥ 50% liver occupation.
• b) Clear invasion into the bile duct.
• c) Portal vein invasion at the main portal branch (Vp4).
• Patients who have received any systemic chemotherapy, including sorafenib, or immunotherapy, or any systemic investigational anticancer agents for advanced/unresectable HCC.
• Note: Patients who have received local hepatic injection chemotherapy are eligible.
• Patients 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 enrolment.
• Patients who have not recovered from toxicities as a result of prior anticancer therapy, except alopecia and infertility.
• Recovery is defined as < Grade 2 severity per Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).
• Patients 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.
• Patients 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 INR monitoring (treatment with low molecular weight heparin is allowed).
• Patients having a gastrointestinal bleeding event or active haemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to enrolment.
• Patients with gastric or oesophageal varices that may require treatment.
• Patients 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.
• Patients having > 1 + proteinuria on urine dipstick testing will undergo 24 h urine collection for quantitative assessment of proteinuria.
• Patients with urine protein ≥ 1 g/24 h will be excluded.
• Any medical or other condition that in the opinion of the Investigator would preclude the patient’s participation in the study.
• Patients with known intolerance to Lenvatinib (or any of the excipients).
• Patients with positive human immunodeficiency virus (HIV) or active infection requiring treatment (except for hepatitis virus).
• Patients who cannot be evaluated by either triphasic liver CT or triphasic liver MRI because of allergy or other contraindication to both CT and MRI contrast agents.
• Patients who have undergone major surgery within 3 weeks prior to the entry in the study or are scheduled for a surgery during the study period.
• Female patients who are breastfeeding or pregnant at the time of enrolment in the study.
• Female patients of childbearing potential who, within 4 weeks prior to study enrolment, did not use a highly effective method of contraception or do not agree to use a highly effective method of contraception throughout the study period.
• Current abuse of alcohol; and current or past (last 12 months) abuse of drugs.
• Participation in a concurrent clinical trial or in another trial within the 6 months prior to this study enrolment.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Rate of treatment-emergent adverse events (TEAE) with Common Terminology Criteria for Adverse Events (CTCAE) grades ≥ 3 within 24 weeks from the start of the treatment.	Rate of treatment-emergent adverse events (TEAE) with Common Terminology Criteria for Adverse Events (CTCAE) grades ≥ 3 within 24 weeks from the start of the treatment.

Secondary Outcome Measures

Name	Time	Method
Objective response rate (ORR), as measured according to the RECIST 1.1 criteria, as the best objective response within 24 weeks from the start of the treatment.	Progression-free survival (PFS) defined as the time from the start of treatment until the first occurrence of disease progression or death, whichever is earlier.

Trial Locations

Locations (11)

Apex Wellness Hospital; 🇮🇳 Nashik, MAHARASHTRA, India

Apollo Gleneagles Hospital Limited; 🇮🇳 Kolkata, WEST BENGAL, India

Asian Institute of Gastroenterology Hospitals; 🇮🇳 Hyderabad, TELANGANA, India

HCG Comprehensive Cancer Care Hospital; 🇮🇳 Bangalore, KARNATAKA, India

HCG Manavata Cancer Centre; 🇮🇳 Nashik, MAHARASHTRA, India

King Georges Medical University (KGMU; 🇮🇳 Lucknow, UTTAR PRADESH, India

LMMFs Deenanath Mangeshkar Hospital & Research center; 🇮🇳 Pune, MAHARASHTRA, India

Meenakshi Mission Hospital; 🇮🇳 Madurai, TAMIL NADU, India

Noble Hospital Pvt Ltd; 🇮🇳 Pune, MAHARASHTRA, India

Somani Hospital,; 🇮🇳 Jaipur, RAJASTHAN, India

Scroll for more (1 remaining)

Apex Wellness Hospital

🇮🇳Nashik, MAHARASHTRA, India

Dr Shailesh Bondarde

Principal investigator

9822012427

shaileshbondarde1971@gmail.com