Clinical Trials /

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

NCT04425226

Description:

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

N/A

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab and LENvatinib in Participants With Hepatocellular Carcinoma (HCC) Before Liver Transplant
  • Official Title: Safety and Efficacy Study of Pembrolizumab in Combination With LENvatinib in Participants With Hepatocellular Carcinoma (HCC) Before Liver Transplant as Neoadjuvant TherapY——PLENTY Randomized Clinical Trial

Clinical Trial IDs

  • ORG STUDY ID: Renji-IIT-2020-0005
  • NCT ID: NCT04425226

Conditions

  • Liver Transplant; Complications
  • Hepatocellular Carcinoma Recurrent

Interventions

DrugSynonymsArms
Pembrolizumab Injection [Keytruda]Keytruda, MK-3475, PembrolizumabPembrolizumab plus Lenvatinib
Lenvatinib Oral ProductLENVIMA, LenvatinibPembrolizumab plus Lenvatinib

Purpose

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.

Detailed Description

      Participates would be randomly assigned (1:1) to experimental or Comparator/Control by
      computer-generated allocation based on the envelope method and the hierarchical block
      randomization method. The envelopes are sealed opaque, and sequentially
      numbered.Randomization is performed by the trial coordinator.The random number table and the
      block assignment number table will be kept confidential by the full-time secretary of this
      project.Center-stratified block-permuted randomization is used in this trial. Then permuted
      block randomization is used for each stratum with a block size of 4.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab plus LenvatinibExperimentalParticipants receive intravenous (IV) pembrolizumab at 200 mg on Day 1 of each 21-day cycle. Number of cycles: until >42 days before liver transplantation or unacceptable toxicity develops. Patients receive Lenvatinib 8-12mg(basing on weight), once a day, oral at least 38 days of each 6 weeks cycle until >7 days before liver transplantation.
  • Pembrolizumab Injection [Keytruda]
  • Lenvatinib Oral Product
ComparatorNo InterventionParticipants are advised to stay as healthy as possible and wait regularly

    Eligibility 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 liver score (5 to 6 points) within 7 days prior to Cycle 1, Day 1.
    
              -  Has alpha fetoprotein (AFP) concentration lower than 400 ng/mL within 28 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 2 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 local therapy to liver ablation other than with radiofrequency or
                 microwave ablation.
    
              -  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.
          
    Maximum Eligible Age:80 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Recurrence-Free Survival (RFS)
    Time Frame:Up to ~4 years
    Safety Issue:
    Description:RFS is defined as the time from randomization to first documentation of disease recurrence (local, regional, or distant) as assessed by BICR or by pathology consistent with HCC if required per the site's standard of care, or death due to any cause (both cancer and non-cancer causes of death)

    Secondary Outcome Measures

    Measure:Disease Control Rate (DCR)
    Time Frame:one year
    Safety Issue:
    Description:Proportion of patients whose tumor volume control (reduced or enlarged) reaches a predetermined value and can maintain a minimum time limit.
    Measure:Percentage of Participants who Experience an Adverse Event (AE)
    Time Frame:one year
    Safety Issue:
    Description:An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
    Measure:Percentage of Participants who Discontinue Study Treatment due to an AE
    Time Frame:Up to ~1 year
    Safety Issue:
    Description:An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.

    Details

    Phase:N/A
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:RenJi Hospital

    Last Updated

    June 24, 2020