AzTrials
AzTrials

Carcinoma, HepatocellularPhase 2NeoLeap-HCCNCT05389527

Pembrolizumab and Lenvatinib for Resectable Hepatocellular Carcinoma

A Phase 2 study testing Pembrolizumab+Lenvatinib in people with Carcinoma, Hepatocellular, run by Shanghai Zhongshan Hospital at 4 sites in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

This is an open-label, multi-center, single-arm, phase II study to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab as a neoadjuvant therapy in subjects with resectable hepatocellular carcinoma (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?
Pembrolizumab+Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
4 sitesChina
Study dates
30 Sep 2022to 31 Jul 2025
Phase
Phase 2
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

  • Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically/cytologically or clinically (according to American Association for the Study of Liver Diseases (AASLD) criteria) confirmed diagnosis of HCC, excluding fibrolamellar sarcomatoid or mixed cholangiocarcinoma-hepatocellular carcinoma.
  • Have not received any locoregional or systemic treatment before enrolment. Patients had recurrence for more than 2 years after the previous surgery could be included.
  • Tumor within Milan criteria should be accompanied with microvascular invasion (judged by radionics nomogram of Fudan Zhongshan Hosp); Or beyond Milan criteria without extrahepatic metastasis.
  • Resectable disease as judged by a multidisciplinary treatment group.
  • Child-Pugh A.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1 and performed within 7 days prior to date of enrolment.
Show all 16Show fewer
  • In case of hepatitis B virus (HBV) positive (HBsAg (+)) subjects:
  • HBV DNA < 2000 IU/mL within 28 days before treatment; subjects received anti-HBV therapy should stay on the same therapy throughout study treatment.
  • Subjects with HBV DNA > 2000 IU/mL without anti-HBV therapy, should receive anti-HBV therapy and stay the same therapy throughout study treatment, and 2 days before treatment, the HBV DNA should decrease for at least 1 log.
  • Subjects with HBV DNA > 2000 IU/mL with anti-HBV therapy, should receive anti-HBV therapy and stay the same therapy throughout study treatment, and 2 days before treatment, the HBV DNA should decrease at least 1 log.
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at Screening and no change in antihypertensive medications within 1 week prior to the treatment.
  • Have measurable disease based on RECIST 1.1.
  • Have adequate organ function. Specimens collected within 7 days prior to start of study treatment.
  • Male participants: A male participant must agree to use a contraception of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants: A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
  • The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

Who cannot join

  • Imaging findings for HCC of clear invasion into the bile duct or portal vein invasion with Vp4.
  • Positive pregnancy test in female patients with childbearing potential within 72 hours prior to enrollment.
  • Prior anticancer treatment or any investigational agent.
  • Subjects having ≥2+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. Subjects with urine protein ≥1 g/24-hour will be ineligible.
  • Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
  • New York Heart Association congestive heart failure of grade II or above, unstable angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia associated with significant cardiovascular impairment within the past 6 months.
Show all 17Show fewer
  • Prolongation of corrected QT (QTc , Fridericia formula) interval to >480 ms.
  • Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
  • Bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants requiring therapeutic international normalized ratio (INR) monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin is permitted. Antiplatelet agents are prohibited throughout the study.
  • Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.
  • Subject is known to be positive for Human Immunodeficiency Virus (HIV).
  • Serious nonhealing wound, ulcer, or bone fracture.
  • History of solid organ or hematologic transplant.
  • Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
  • Active, known or suspected autoimmune disease that has required systemic treatment in the past 2 years or a documented history of clinically severe autoimmune disease, or any other syndrome that requires systemic steroids or immunosuppressive agents, patients with hypothyroidism stable on hormone replacement, or type 1 diabetes on insulin replacement will not be excluded from the study.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis or has a history of interstitial lung disease.
  • Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

Trial locations and contacts

4 sites in 1 country.

China4 sites

  • The first affiliated hospital, Yat-sen university

    Guangzhou

  • Zhongshan hospital

    Shanghai, Shanghai Municipality, 200032

  • Eastern Hepatobiliary Surgery Hospital

    Shanghai, Shanghai Municipality

  • Ruijin Hospital

    Shanghai, Shanghai Municipality

Other trials in China

About this study

Official title: Efficacy and Safety of the Combination of Pembrolizumab and Lenvatinib as Neoadjuvant Treatment for Hepatocellular Carcinoma Patients

This is an open-label, multi-center, single-arm, phase II study to evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab as a neoadjuvant therapy in subjects with resectable hepatocellular carcinoma (HCC).

Read the detailed description

The recurrence rate of hepatocellular carcinoma (HCC) after curative surgery is high and the survival benefit is limited. Neoadjuvant therapy, by targeting the disseminated tumor cells before curative surgery, may lower the incidence of tumor recurrence. In KEYNOTE-524 study, lenvatinib plus pembrolizumab combination showed promising efficacy and manageable toxicity. This study will evaluate the efficacy and safety of lenvatinib in combination with pembrolizumab as a neoadjuvant therapy in subjects with resectable HCC.

Being tested
Pembrolizumab+Lenvatinib
Keywords
Hepatocellular carcinoma, Neoadjuvant therapy, Pembrolizumab, Lenvatinib
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Pembrolizumab+LenvatinibDrug

    After enrollment, subjects receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for 9 weeks: Lenvatinib 8 mg (body weight <60 kg) or 12 mg (body weight ≥60 kg) orally once daily for 9 weeks.

    Subjects conduct surgery 1 week after the last dose of Lenvatinib. 4 weeks after surgery, Pembrolizumab and Lenvatinib will restart as adjuvant treatment for up to 1 year.

Study groups in NCT05389527
Study groupRoleWhat they receive
experimental armExperimentalPembrolizumab+Lenvatinib
Receives: Drug: Pembrolizumab+Lenvatinib

What is being measured

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

  1. Major pathological response (MPR)

    Defined as ≤ 50% viable tumor cells pathologically in the resected specimen.

    Measured: up to 24 weeks

Secondary outcomes (7)

  1. Pathologic complete response (pCR)

    Defined as complete absence of residual visible tumor in resected tissues.

    Measured: up to 24 weeks

  2. Objective response rate (ORR)

    Defined as the proportion of the subjects who have a complete response (CR) and partial response (PR) per RECIST 1.1 in enrolled subjects

    Measured: up to 24 weeks

  3. R0 resection rate

    Defined as the proportion of patients who have microscopically margin-negative resection, in which no gross or microscopic tumor remains in the primary tumor bed in enrolled subjects.

    Measured: up to 24 weeks

  4. Disease-free survival (DFS)

    Defined as the time from surgery to first documented recurrence or death due to any cause, whichever occurs first based on RECIST 1.1 in population underwent surgery

    Measured: up to 2 years

  5. 1-year DFS rate

    Defined as the estimated proportion of patients who have no recurrence or death at 1 year after liver resection.

    Measured: up to 2 years

  6. Overall survival

    Defined as the time from enrollment to death due to any cause in enrolled subjects.

    Measured: up to 2 years

  7. Adverse event (AE)

    Adverse events (AEs) ; serious adverse events (SAEs); abnormal value of Lab test according to NCI-CTCAE V5.0.

    Measured: up to 2 years

Timeline

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

  1. First posted25 May 2022
  2. Study start30 Sep 2022
  3. Primary completion15 Dec 2023
  4. Study completion31 Jul 2025 (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
43 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05389527
Sponsor's protocol ID
NeoLeap-HCC
Acronym
NeoLeap-HCC
Status last verified
Jul 2024
First submitted
20 May 2022
Last updated
11 Jul 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bruix J, Sherman M; American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: an update. Hepatology. 2011 Mar;53(3):1020-2. doi: 10.1002/hep.24199. No abstract available.

    PubMed 21374666

  • Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.

    PubMed 32716739

  • Pinato DJ, Fessas P, Sapisochin G, Marron TU. Perspectives on the Neoadjuvant Use of Immunotherapy in Hepatocellular Carcinoma. Hepatology. 2021 Jul;74(1):483-490. doi: 10.1002/hep.31697. Epub 2021 Jun 28. No abstract available.

    PubMed 33369758

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab+Lenvatinib in people with Carcinoma, Hepatocellular, run by Shanghai Zhongshan Hospital at 4 sites in China.

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 16 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 11 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 4 sites in China. 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?

Results are not available in the source record.

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?

Major pathological response (MPR) (time frame: up to 24 weeks). 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 NCT05389527, which also lists 3 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 11 Jul 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in