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Hepatocellular CarcinomaPhase 2NCT06138769

Lenvatinib After Progression on Atezolizumab-bevacizumab in Hepatocellular Carcinoma

A Phase 2 study testing Lenvatinib in people with Hepatocellular Carcinoma, run by Asan Medical Center at 1 site in South Korea.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Although atezolizumab-bevacizumab has been positioned as the standard first-line therapy in unresectable heptocellular carcinoma, eventually most patients progressed on this regimen. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Hepatocellular Carcinoma
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
1 siteSouth Korea
Study dates
20 Jul 2023to 1 Nov 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of HCC according to AASLD guidelines
  • Disease that is not amenable to a curative treatment (e.g. surgery, transplant, radiofrequency ablation)
  • Prior treatment with atezolizumab plus bevacizumab as first-line treatment for unresectable HCC
  • Progression after atezolizumab plus bevacizumab, the duration of these treatments must be 2 consecutive treatment cycles or more.
  • At least 1 RECIST v1.1 measurable untreated lesion
  • Recovery to ≤ Grade 1 from toxicities related to any prior treatments, unless the adverse events are clinically non-significant and/or stable on supportive therapy
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  • Life expectancy of 12 weeks or longer
  • Age ≥ 19 years old
  • ECOG performance status of 0, 1
  • Adequate hematological function
  • Absolute neutrophil count (ANC) ≥ 1.0 x109/L
  • Platelets ≥ 75 x 109/L
  • Hemoglobin ≥ 10 g/dL
  • Adequate renal function
  • serum creatinine ≤ 1.5 × upper limit of normal or calculated creatinine clearance ≥ 40 mL/min (using the Cockroft-Gault equation) AND
  • urine protein/creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol) or 24-hour urine protein < 1 g
  • Child-Pugh Score of 5 or 6
  • Total bilirubin ≤ 2 mg/dL (≤ 34.2 μmol/L)
  • Serum albumin > 2 g/dL (> 20 g/L)
  • Alanine aminotransferase (ALT) < 3.0 upper limit of normal (ULN)
  • Antiviral therapy per local standard of care if active hepatitis B (HBV) infection
  • Capable of understanding and complying with the protocol requirements and signed informed consent
  • Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment
  • Females of child-bearing potential must be willing to use effective contraception during study and for 30 days after the last dose.

Who cannot join

  • Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma
  • Prior lenvatinib treatment
  • Prior systemic treatment for HCC, except for atezolizumab plus bevacizumab (i.e. lenvatinib must be second-line systemic treatment)
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 3 months before randomization.
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders including i. Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
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  • Uncontrolled blood pressure (Systolic BP>150 mmHg or diastolic BP >90 mmHg) in spite of an optimized regimen of antihypertensive medication.
  • Stroke (including TIA), myocardial infarction, or other ischemic event within 6 months iv. Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
  • Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation/bleeding: i. Tumors invading the GI tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction ii. Abdominal fistula, GI perforation, bowel obstruction, intra-abdominal abscess within 6 months
  • Major surgery within 2 months before randomization. Complete healing from major surgery must have occurred 1 month before randomization. Complete healing from minor surgery (eg, simple excision, tooth extraction) must have occurred at least 7 days before registration. Subjects with clinically relevant co d. Cavitating pulmonary lesion(s) or endobronchial disease
  • Moderate or severe ascites (Radiologically detected but clinically insignificant ascites is allowed)
  • Corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 21 days of registration
  • If the QTcF is > 500 ms in first ECG, a total of 3 ECGs should be performed. If the average of these 3 consecutive results for QTcF is ≤ 500 ms, the subject meets eligibility in this regard.
  • Subjects having > 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations
  • Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] (or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]).
  • Diagnosis of another malignancy within 2 years before randomization, except for superficial skin cancers, or localized, low-grade tumors deemed cured and not treated with systemic therapy
  • Electrolyte abnormalities that have not been corrected.
  • Subjects who have not recovered adequately from any toxicity from other anti- cancer treatment regimens and/or complications from major surgery prior to starting therapy. Withhold lenvatinib for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
  • The participant has severe hypersensitivity (≥Grade 3) to lenvatinib and/or any of its excipients.
  • Other clinically significant disorders that are judged by investigators to be unsuitable for the clinical trial

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

About this study

Official title: Multicenter Phase 2 Trial of Lenvatinib in Patients With Unresectable or Metastatic Hepatocellular Carcinoma After Progression on First-line Atezolizumab Plus Bevacizumab

Although atezolizumab-bevacizumab has been positioned as the standard first-line therapy in unresectable heptocellular carcinoma, eventually most patients progressed on this regimen. Despite of multiple drugs are approved for the management of unresectable hepatocellular carcinoma, only a few trials have been conducted to investigate their efficacy in the second-line setting after the progression on atezolizumab-bevacizumab. Lenvatinib is approved first-line multikinase inhibitor in unresectable hepatocellular carcinoma, but has not yet been investigated as second-line therapy in prospective study. In this single arm phase 2 study, the efficacy and safety of lenvatinib will be investigated for patients who progressed on first-line atezolizumab-bevacizumab.

Being tested
Lenvatinib
Keywords
hepatocellular carcinoma, lenvatinib, atezolizumab-bevacizumab
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 12 mg (body weight 60 kg or greater) or 8 mg (body weight < 60 kg) once orally every day

Study groups in NCT06138769
Study groupRoleWhat they receive
LenvatinibExperimentalLenvatinib 12 mg (body weight 60 kg or greater) or 8 mg (body weight < 60 kg) once orally every day
Receives: Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival

    Time interval between the start of lenvatinb to the disease progression or any cause of death.

    Measured: 1 year

Secondary outcomes (4)

  1. Overall survival

    Time interval between the start of lenvatinib to the any cause of death

    Measured: 1 year

  2. Overall response rate

    Proportion of complete response or partial response according to the Response Evaluation Criteria for Solid Tumor version 1.1

    Measured: 1 year

  3. Disease control rate

    Proportion of complete response, partial response or stable disease according to the Response Evaluation Criteria for Solid Tumor version 1.1

    Measured: 1 year

  4. Adverse events

    Common Toxicity Criteria for Adverse Events version 5

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Nov 2023
  2. Study start20 Jul 2023
  3. Primary completion1 Nov 2026 (estimated)
  4. Study completion1 Nov 2027 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06138769
Sponsor's protocol ID
LENVINEXT
Status last verified
Jun 2024
First submitted
14 Nov 2023
Last updated
3 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: It will be determined after the analysis of the primary data.

Publications

  • Kudo M, Finn RS, Qin S, Han KH, Ikeda K, Piscaglia F, Baron A, Park JW, Han G, Jassem J, Blanc JF, Vogel A, Komov D, Evans TRJ, Lopez C, Dutcus C, Guo M, Saito K, Kraljevic S, Tamai T, Ren M, Cheng AL. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018 Mar 24;391(10126):1163-1173. doi: 10.1016/S0140-6736(18)30207-1.

    PubMed 29433850

  • Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL; IMbrave150 Investigators. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020 May 14;382(20):1894-1905. doi: 10.1056/NEJMoa1915745.

    PubMed 32402160

  • Vogel A, Cervantes A, Chau I, Daniele B, Llovet JM, Meyer T, Nault JC, Neumann U, Ricke J, Sangro B, Schirmacher P, Verslype C, Zech CJ, Arnold D, Martinelli E; ESMO Guidelines Committee. Hepatocellular carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv238-iv255. doi: 10.1093/annonc/mdy308. No abstract available.

    PubMed 30285213

  • Kim HD, Sym SJ, Chon HJ, Kim M, Kang JH, Ryoo BY, Lee CK, Hong J, Ryu H, Bae WK, Kim H, Kim H, Kim JW, Kim TY, Yoo C. Multicenter single-arm phase II trial of lenvatinib in patients with advanced hepatocellular carcinoma after progression on first-line atezolizumab plus bevacizumab. J Hepatol. 2026 Feb;84(2):308-315. doi: 10.1016/j.jhep.2025.08.020. Epub 2025 Sep 4.

    PubMed 41038766

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lenvatinib in people with Hepatocellular Carcinoma, run by Asan Medical Center at 1 site in South Korea.

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 24 inclusion and 21 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: under way, not looking for participants, as of the sponsor's last update on 3 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Progression-free survival (time frame: 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06138769, which also lists 4 linked publications.

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 3 Jul 2024.

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