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

NCT04425226 | Unknown DMC

• 1 other identifier: Renji-IIT-2020-0005
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Liver Transplant; Complications; Hepatocellular Carcinoma Recurrent

Outcome Measures

Primary Outcomes (1)

• Recurrence-Free Survival (RFS)

  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)

  Up to ~4 years

Secondary Outcomes (4)

• Disease Control Rate (DCR)

  one year

• Percentage of Participants who Experience an Adverse Event (AE)

  one year

• Percentage of Participants who Discontinue Study Treatment due to an AE

  Up to ~1 year

• Objective Response Rate (ORR)

  one year

Study Arms (2)

Pembrolizumab plus Lenvatinib

EXPERIMENTAL

Participants 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.

Drug: Pembrolizumab Injection [Keytruda]; Drug: Lenvatinib Oral Product

Comparator

NO INTERVENTION

Participants are advised to stay as healthy as possible and wait regularly

Interventions

Pembrolizumab Injection [Keytruda] DRUG

Pembrolizumab (Keytruda, MSD China) is a recombinant anti-human PD-1 monoclonal antibody.

Also known as: Keytruda, MK-3475, Pembrolizumab

Pembrolizumab plus Lenvatinib

Lenvatinib Oral Product DRUG

Lenvatinib (Lenvima, Eisai China) is a novel angiogenesis inhibitor which targets vascular endothelial growth factor 1-3, fibroblast growth factor receptor 1-4, platelet-derived growth factor receptor β, RET and KIT

Also known as: LENVIMA, Lenvatinib

Pembrolizumab plus Lenvatinib

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University

Shanghai, 200127, China

RECRUITING

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Study Officials

• Qiang Xia, MD., Ph.D.

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  STUDY CHAIR

• Hao Feng, MD., Ph.D.

  Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hao Feng, MD., Ph.D.

CONTACT

008615000901110; surgeonfeng@live.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2020
• First Posted: June 11, 2020
• Study Start: August 6, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2024
• Last Updated: August 13, 2020

Record last verified: 2020-08

Locations

CN (1)