Carcinoma, HepatocellularPhase 4NCT04297254
A Study to Assess the Safety and Efficacy of Lenvatinib as First-line Treatment in Participants With Unresectable HCC
A Phase 4 study testing Lenvatinib in people with Carcinoma, Hepatocellular, run by Eisai Pharmaceuticals India Pvt. Ltd at 10 sites in India.
Trial summary
The primary objective of this study is to evaluate the safety of lenvatinib in HCC. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Lenvatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 10 sitesIndia
- Study dates
- 4 Feb 2021to 31 Jul 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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:
- Absolute neutrophil count (ANC) >= 1.5*10^9 per liter (/L)
- Haemoglobin >=8.5 gram per deciliter (g/dL)
- Platelet count >=75*10^9/L
- Adequate liver function based on liver function tests, defined as:
- Albumin >=2.8 g/dL
- Bilirubin less than or equal to <=3.0 milligram per deciliter (mg/dL)
- Aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) <=5*the upper limit of normal (ULN)
- Adequate blood coagulation function, defined as international normalized ratio (INR) <=2.3
- Adequate renal function, defined as >30 milliliter per minute (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 millimeter of mercury (mmHg) 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
- With a Child-Pugh score A
- With Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- With life expectancy of >=12 weeks from the start of study treatment, as per Investigator's judgement.
Who cannot join
- 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
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- 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
- Having >1 + proteinuria on urine dipstick testing will undergo 24 hour (h) urine collection for quantitative assessment of proteinuria. Patients with urine protein >=1 gram per 24 hour (g/24 h) will be excluded
- With arterial-portal venous shunt or arterial-venous shunt preventing a proper diagnosis of the tumour
- Any medical or other condition that in the opinion of the Investigator would preclude the participant's participation in the study.
- With known intolerance to lenvatinib (or any of the excipients)
- With positive human immunodeficiency virus (HIV) or active infection requiring treatment (except for hepatitis virus)
- Who cannot be evaluated by either triphasic liver computed tomography (CT) or triphasic liver magnetic resonance imaging (MRI) because of allergy or other contraindication to both CT and MRI contrast agents
- Have undergone major surgery within 3 weeks prior to the entry in the study or are scheduled for a surgery during the study period
- Have already undergone a liver transplant
- Female participants who are breastfeeding or pregnant at the time of enrolment in the study
- Female participants 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
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
India10 sites
HCG Comprehensive Cancer Care Hospital
Bangalore, Karnataka, 560027
Somani Hospital
Jaipur, Rajasthan, 302019
Apollo Gleneagles Hospital Limited
Kolkata, West Bengal, 700054
Meenakshi Mission Hospital
Madurai, Tamil Nadu, 625107
Tata Memorial Hospital
Mumbai, Maharashtra, 400012
HCG Manavata Cancer Centre
Nashik, Maharashtra, 422002
Shatabdi Hospital
Nashik, Maharashtra, 422005
Apex Wellness Hospital
Nashik, Maharashtra, 422009
LMMF's Deenanath Mangeshkar Hospital & Research Center
Pune, Maharashtra, 411004
Noble Hospital
Pune, Maharashtra, 411013
About this study
Official title: A Prospective, Multicenter, Post-marketing Phase IV Study to Assess the Safety and Efficacy of Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma (HCC)
The primary objective of this study is to evaluate the safety of lenvatinib in HCC.
Read the detailed description
This is a prospective, multi-center, open-label, single-arm, non-comparative, post-marketing phase IV study. This study will enroll 50 participants with unresectable HCC. Participants will receive lenvatinib for 24 weeks or until disease progression, death, intolerable or unacceptable toxicity, or withdrawal of consent, whichever occurs earlier. All participants will be followed up for an end-of-study (EOS) visit at 4 weeks after the completion of 24 weeks of treatment or after last treatment visit if earlier, as applicable that is end-of-treatment (EOT).
Participants who completed 24 weeks of therapy and continue to show clinical benefit will be able to continue to receive lenvatinib (beyond week 24 as necessary) as per Investigator's discretion and based on radiological response.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Lenvatinib
- Keywords
- Lenvatinib, E7080, Unresectable hepatocellular carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Lenvatinib capsules.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Lenvatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Baseline up to Week 24
Number of Participants with Serious Adverse Events (SAEs)
Measured: 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).
Measured: Baseline up to Week 24
Secondary outcomes (4)
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with complete response (CR) or partial response (PR) as the best overall response from the start of study treatment up to Week 24. CR per response evaluation criteria in solid tumor (RECIST) 1.1 is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR per RECIST 1.1 is defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the start of study treatment up to Week 24
Progression-free Survival (PFS)
PFS is defined as the time from the start of treatment until the first occurrence of disease progression (PD) or death, whichever is earlier. PD per RECIST 1.1 is defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.
Measured: 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)
Measured: Baseline up to Week 24
Time to First Dose Reduction
Measured: Baseline up to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2020
- Study start4 Feb 2021
- Primary completion31 Jul 2023
- Study completion31 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Pharmaceuticals India Pvt. Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04297254
- Sponsor's protocol ID
- E7080-M091-511
- Status last verified
- Feb 2023
- First submitted
- 4 Mar 2020
- Last updated
- 15 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Multicenter, Post-marketing Phase IV Study to Assess the Safety and Efficacy of Lenvatinib as First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT04297254
- Acronym / sponsor ID
- E7080-M091-511
- Conditions
- Carcinoma, Hepatocellular
- Keywords
- Lenvatinib, E7080, Unresectable hepatocellular carcinoma
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Eisai Pharmaceuticals India Pvt. LtdIndustry (pharma, biotech, devices)
- Study start
- 4 Feb 2021 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 5 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety of lenvatinib in HCC.
Detailed description
This is a prospective, multi-center, open-label, single-arm, non-comparative, post-marketing phase IV study. This study will enroll 50 participants with unresectable HCC. Participants will receive lenvatinib for 24 weeks or until disease progression, death, intolerable or unacceptable toxicity, or withdrawal of consent, whichever occurs earlier. All participants will be followed up for an end-of-study (EOS) visit at 4 weeks after the completion of 24 weeks of treatment or after last treatment visit if earlier, as applicable that is end-of-treatment (EOT).
Participants who completed 24 weeks of therapy and continue to show clinical benefit will be able to continue to receive lenvatinib (beyond week 24 as necessary) as per Investigator's discretion and based on radiological response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib 12 mg or 8 mg | Experimental | Drug: LenvatinibParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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:
- At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:
- Participants are categorized to Stage B (not applicable for transarterial chemoembolization [TACE]) or Stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system.
Key exclusion criteria (27 listed)
- With imaging findings for HCC corresponding to any of the following:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibLenvatinib capsules. | Drug | Lenvatinib 12 mg or 8 mg |
Primary outcome
Percentage of Participants with Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Week 24
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).
Number of Participants with Serious Adverse Events (SAEs)
Time frame: Baseline up to Week 24
Number of Participants with Grades 1 and 2 Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Week 24
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).
4 secondary outcomes
Objective Response Rate (ORR)
Time frame: From the start of study treatment up to Week 24
Progression-free Survival (PFS)
Time frame: 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)
Time frame: Baseline up to Week 24
Time to First Dose Reduction
Time frame: Baseline up to Week 24
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2023.
- Individual participant dataSharing planned: Yes. Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Lenvatinib in people with Carcinoma, Hepatocellular, run by Eisai Pharmaceuticals India Pvt. Ltd at 10 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants with Grade 3 or Higher Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline up to Week 24). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2023.