- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05389527
Pembrolizumab and Lenvatinib for Resectable Hepatocellular Carcinoma (NeoLeap-HCC)
The Combination of Pembrolizumab and Lenvatinib as Neoadjuvant Treatment for Hepatocellular Carcinoma Patients: a Single Arm Phase II Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Guangzhou, China
- The first affiliated hospital, Yat-sen university
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Shanghai
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Shanghai, Shanghai, China, 200032
- Zhongshan Hospital
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Shanghai, Shanghai, China
- Eastern Hepatobiliary Surgery Hospital
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Shanghai, Shanghai, China
- Ruijin Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: experimental arm
Pembrolizumab+Lenvatinib
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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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Major pathological response (MPR)
Time Frame: up to 24 weeks
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Defined as ≤ 50% viable tumor cells pathologically in the resected specimen.
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up to 24 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pathologic complete response (pCR)
Time Frame: up to 24 weeks
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Defined as complete absence of residual visible tumor in resected tissues.
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up to 24 weeks
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Objective response rate (ORR)
Time Frame: up to 24 weeks
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Defined as the proportion of the subjects who have a complete response (CR) and partial response (PR) per RECIST 1.1 in enrolled subjects
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up to 24 weeks
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R0 resection rate
Time Frame: up to 24 weeks
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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.
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up to 24 weeks
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Disease-free survival (DFS)
Time Frame: up to 2 years
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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
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up to 2 years
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1-year DFS rate
Time Frame: up to 2 years
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Defined as the estimated proportion of patients who have no recurrence or death at 1 year after liver resection.
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up to 2 years
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Overall survival
Time Frame: up to 2 years
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Defined as the time from enrollment to death due to any cause in enrolled subjects.
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up to 2 years
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Adverse event (AE)
Time Frame: up to 2 years
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Adverse events (AEs) ; serious adverse events (SAEs); abnormal value of Lab test according to NCI-CTCAE V5.0.
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up to 2 years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Huichuan Sun, Fudan University
Publications and helpful links
General 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Digestive System Neoplasms
- Liver Diseases
- Liver Neoplasms
- Carcinoma
- Carcinoma, Hepatocellular
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Immune Checkpoint Inhibitors
- Pembrolizumab
- Lenvatinib
Other Study ID Numbers
- NeoLeap-HCC
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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