CTRI/2020/08/027136 [Registered on: 13/08/2020] Trial Registered Prospectively
Last Modified On:
25/07/2022
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Single Arm Study
Public Title of Study
Study in use of Lenvatinib in patients with unable to be removed by surgery Hepatocellular Carcinoma
Scientific Title of Study
A PROSPECTIVE, MULTICENTRE, POST-MARKETING PHASE IV STUDY TO ASSESS THE SAFETY AND EFFICACY OF LENVATINIB AS FIRST-LINE TREATMENT IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA (HCC)
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
E7080-M091-511 Version 1.0 dated 19 Sep 2019
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
DrBalaji Patil
Designation
Head, Medical Affairs
Affiliation
Eisai Pharmaceuticals, India Pvt. Ltd.
Address
6th Floor, A Wing, Marwah Center,
Krishanlal Marwah Marg,
Andheri East, Mumbai .
Mumbai MAHARASHTRA 400072 India
Phone
9004831103
Fax
Email
b-patil@eisaiindia.com
Details of Contact Person Public Query
Name
DrBalaji Patil
Designation
Head, Medical Affairs
Affiliation
Eisai Pharmaceuticals, India Pvt. Ltd.
Address
6th Floor, A Wing, Marwah Center,
Krishanlal Marwah Marg,
Andheri East, Mumbai .
MAHARASHTRA 400072 India
Phone
9004831103
Fax
Email
b-patil@eisaiindia.com
Source of Monetary or Material Support
Eisai Pharmaceuticals, India Pvt. Ltd. 6th Floor, A Wing, Marwah Center,
Krishanlal Marwah Marg,
Andheri East, Mumbai 400072.
Primary Sponsor
Name
Eisai Pharmaceuticals India Pvt Ltd
Address
6th Floor, A Wing, Marwah Center,
Krishanlal Marwah Marg,
Andheri East, Mumbai 400072.
Maharashtra, INDIA.
Institutional Ethics Committee 3rd floor main building, Tata Memorial Hospital Dr. Ernest Borges Marg, Parel Mumbai 400012.
Approved
Institutional Ethics Committee Asian Institute of Gastroenterology Hospitals, No.136, Plot No 2/3/4/5, Survey,1, Mindspace road, Gachibowli, Hyderabad, Telangana, 500032
Approved
Institutional Ethics Committee King Georges Medical University King Georges Medical University,Shahmina Road, Chowk, Lucknow Lucknow Uttar Pradesh - 226003 India
Submittted/Under Review
Institutional Ethics Committee Noble Hospital
Approved
Institutional Ethics Committee Room No.6701, 6th Floor, Meenakshi Mission Hospital & Research Centre, Lake Area, Melur Road, Madurai-625107, Tamil Nadu.
Approved
Institutional Ethics Committee Super Specialty Building, 14th floor, LMMFs Deenanath Mangeshkar Hospital & Research centre, Erandwane, Pune- 411004, Maharashtra.
Approved
Institutional Ethics Committee, Apollo Gleneagles Hospital Limited, Kolkata, 58, Canal Circular Road - 700054, India Kolkata, West Bengal.
Approved
Manavata Clinical Research Institute Ethics Committee 1st floor, behind Shivang auto, Mumbai Naka, Nashik 422002
The dosage of Lenvatinib to be used in the study is as follows: A. Patients with body weight (BW) ≥ 60 kg: 12 mg Lenvatinib daily [3 capsules]
B. Patients with BW 60 kg: 8 mg Lenvatinib daily [2 capsules]
Comparator Agent
NA
NA
Inclusion Criteria
Age From
18.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
1. Males or females of ≥ 18 years of age.
2. 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.
3. 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.
4. 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.
b. 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.
c. Lesions previously treated with radiotherapy or locoregional therapy must show radiographic evidence of disease progression to be deemed a target lesion.
5. Patient is categorized to stage B (not applicable for TACE) or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
6. 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.
7. 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).
8. Adequate blood coagulation function, defined as international normalized ratio (INR) ≤ 2.3.
9. Adequate renal function, defined as > 30 ml/min calculated as per the Cockcroft and Gault formula#.
10. 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.
11. Adequate pancreatic function, defined as amylase and lipase ≤ 1.5 × ULN.
12. Patient with a Child-Pugh score A.
13. Patient with Eastern Cooperative Oncology Group (ECOG) performance status of 0–1.
14. Patient with life expectancy of ≥ 12 weeks from the start of study treatment, as per Investigator’s judgement.
ExclusionCriteria
Details
Patients who meet any of the following criteria will be excluded from this study.
1. 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).
2. 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.
3. 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.
4. 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).
5. 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.
6. Patients with prolongation of QTc interval to > 480 ms.
7. Patients with gastrointestinal malabsorption or any other condition that might affect the absorption of Lenvatinib in the opinion of the Investigator.
8. 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).
9. Patients having a gastrointestinal bleeding event or active haemoptysis (bright red blood of at least 0.5 teaspoon) within 28 days prior to enrolment.
10. Patients with gastric or oesophageal varices that may require treatment.
11. 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.
12. Any history of, or concurrent, brain or subdural metastases.
13. 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.
14. Patients with arterial-portal venous shunt or arterial-venous shunt preventing a proper diagnosis of the tumour.
15. Any medical or other condition that in the opinion of the Investigator would preclude the patient’s participation in the study.
16. Patients with known intolerance to Lenvatinib (or any of the excipients).
17. Patients with positive human immunodeficiency virus (HIV) or active infection requiring treatment (except for hepatitis virus).
18. 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.
19. 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.
20. Patients who have already undergone a liver transplant.
21. Female patients who are breastfeeding or pregnant at the time of enrolment in the study.
22. 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.
23. Current abuse of alcohol; and current or past (last 12 months) abuse of drugs.
24. Participation in a concurrent clinical trial or in another trial within the 6 months prior to this study enrolment.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
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
Outcome
TimePoints
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.
• Proportion of patients requiring dose modifications (dose interruptions or dose reductions).
• The median time to first dose reduction (95% CI).
Target Sample Size
Total Sample Size="50" Sample Size from India="50" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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