Overview

Pembrolizumab and LENvatinib in Participants With Hepatocellular Carcinoma (HCC) Before Liver Transplant

Status:
Recruiting
Trial end date:
2024-12-30
Target enrollment:
0
Participant gender:
All
Summary
Objectives of Study:This study will evaluate the safety and efficacy of pembrolizumab in combination with lenvatinib as neoadjuvant therapy in participants with hepatocellular carcinoma (HCC) exceeding Milan criteria before liver transplant. The primary hypothesis of this study are that neoadjuvant pembrolizumab plus lenvatinib is superior to regularly waiting in the list with respect to: 1) recurrence-free survival (RFS) as assessed by blinded independent central review (BICR); and 2) Objective Response Rate (ORR).The investigators design a clinical study to explore whether the combination above as a neoadjuvant treatment in patients with advanced HCC before liver transplant could reduce postoperative recurrence and to analyze potential immune biomarker of therapeutic response.
Phase:
N/A
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
RenJi Hospital
Treatments:
Lenvatinib
Pembrolizumab
Criteria
Inclusion Criteria:

- Patients must have pathologically or cytologically or by radiological criteria proven
hepatocellular carcinoma(exceeding Milan criteria); known mixed histology (e.g.
hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant is not
allowed

- Has an eligibility scan (CT of the chest, triphasic CT scan or MRI of the abdomen, and
CT or MRI of the pelvis) <1 week before the treatment of pembrolizumab in combination
with lenvatinib. Randomization needs to occur within 1 weeks after recruitment in the
waiting list.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7
days prior to Cycle 1, Day 1.

- Has a Child-Pugh A-B7 liver score (5 to 7 points) within 7 days prior to Cycle 1, Day
1.

- Has controlled hepatitis B (Hep B)

- The estimate time length between enrollment and liver transplantation should be at
least 3 months

- No prior systemic therapy, local therapy (TACE etc.)>6w

- If female, is not pregnant or breastfeeding, and at least one of the following
conditions applies: 1) Is not a woman of childbearing potential (WOCBP); or 2) Is a
WOCBP and using a contraceptive method that is highly effective or be abstinent from
heterosexual intercourse as their preferred and usual lifestyle (a WOCBP must have a
negative pregnancy test within 72 hours before the first dose of study treatment).

- Has adequate organ function.

- Granulocytes >= 1,500/uL

- Hemoglobin >= 8.5 g/dL; patients with recent or ongoing gastrointestinal bleed may not
be transfused to reach the entry hemoglobin of 8.5 g/dL; physicians should ensure
patients requiring transfusion prior to registration do not have an occult or
clinically apparent gastrointestinal bleed

- Platelets >= 75,000/uL

- Creatinine =< 1.5 x upper limit of normal (ULN) (or creatinine clearance calculated >=
60 cc/minute)

- Bilirubin =< 3 mg/dL

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 5 x ULN

- Prothrombin time (PT)-international normalized ratio (INR) =< 1.7 (not required for
patients on anticoagulation agents; patients who are being therapeutically
anticoagulated with an agent such as Coumadin or heparin will be allowed to
participate provided that no prior evidence of underlying abnormality in these
parameters exists)

- Patients with a history of hypertension should be well controlled (< 140/90 mmHg) on a
regimen of anti-hypertensive therapy

- Significant history of cardiac disease is not allowed:

- Congestive heart failure > class II New York Heart Association (NYHA) Myocardial
infarction within 6 months prior to registration Serious myocardial dysfunction,
defined as scintigraphically (multigated acquisition scan [MUGA], myocardial
scintigram) determined absolute left ventricular ejection fraction (LVEF) below 45% or
an LVEF on echocardiogram (ECHO) below the normal limit at the individual institution

Exclusion Criteria:

- Surgery within the past 3 years.

- Has had esophageal or gastric variceal bleeding within the last 6 months.

- Has clinically apparent ascites on physical examination.

- Has had clinically diagnosed hepatic encephalopathy in the last 6 months.

- Has received liver ablation, radiofrequency or microwave ablation, radiotherapy in the
last 6 months.

- Has a history of (noninfectious) pneumonitis that required steroids or has current
pneumonitis

- Has an active infection requiring systemic therapy.

- Has dual active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infection at study
entry.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has known active tuberculosis (TB; Bacillus tuberculosis).

- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX-40, CD137).

- Has received prior systemic anti-cancer therapy for HCC including investigational
agents.

- Is receiving any of the following prohibited concomitant therapies:1) Antineoplastic
systemic chemotherapy or biological therapy; 2) Immunotherapy not specified in this
protocol; 3) Investigational agents other than pembrolizumab; 4) Radiation therapy; 5)
Oncological surgical therapy; or systemic glucocorticoids for any purpose other than
to modulate symptoms from an AE that is suspected to have an immunologic etiology.

- Has received a live vaccine within 30 days prior to the first dose of study treatment.

- Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to Cycle 1, Day 1.

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to Cycle 1, Day 1.

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

- Has an active autoimmune disease that has required systemic treatment in past 2 years.

- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.

- Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 120 days
after the last dose of study treatment.