IMRT Plus PD-1 Blockade and Lenvatinib for HCC With PVTT (Vp3) Before Liver Transplantation

NCT05339581 | Unknown

• 1 other identifier: Renji-IIT2022-011
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

This is a parallel assigned, open-label, perspective trial studying the safety and efficacy of intensity-modulated radiotherapy (IMRT) combined with PD-1 Blockade and Lenvatinib for Hepatocellular Carcinoma (HCC) with Vp3 Portal Vein Tumor Thrombus (PVTT, Japanese Liver Cancer Study Group classification) before liver transplantation.

Conditions

Liver Cancer; Liver Transplant; Complications; Hepatocellular Carcinoma; Portal Vein Thrombosis; Radiotherapy; Complications

Outcome Measures

Primary Outcomes (1)

• PVTT RR/NR

  Portal vein tumor thrombus related Response and Necrosis Rate

  up to 12 months

Secondary Outcomes (5)

• Alpha Fetoprotein Response (AFP-R)

  up to 12 months

• Progression-free survival (PFS)

  up to 12 months

• Objective Response Rate (ORR)

  up to 12 months

• Time to Progression (TTP)

  up to 12 months

• Duration of response (DOR)

  up to 12 months

Study Arms (2)

IMRT combined with PD-1 Blockade and Lenvatinib

EXPERIMENTAL

Participants receive PD-1 Blockade (Pembrolizumab，Sintilimab， Camrelizumab，Tislelizumab) 200 mg intravenously on day 1 of a 21-day treatment cycle until \>42 days before liver transplantation or unacceptable toxicity develops. Participants receive Lenvatinib Mesylate Capsule (Lenvima®) 8 mg orally once daily until \>7 days before liver transplantation. Neoadjuvant IMRT will be initiated at the third treatment cycle, and the dose prescription of IMRT is for planning target volume (PTV). The prescription dose to 95%PTV should be ≥50 Gy and ≤60 Gy, and been given in daily dose fractions of 2 Gy, 5 days per week. And the final prescription dose is determined according to dose constraints for organs at risk.

Radiation: intensity-modulated radiotherapy; Combination Product: Pembrolizumab; Drug: Sintilimab; Drug: Camrelizumab; Drug: Tislelizumab; Drug: Lenvatinib Mesylate Capsule

PD-1 Blockade and Lenvatinib

ACTIVE COMPARATOR

Participants receive PD-1 Blockade (Pembrolizumab，Sintilimab， Camrelizumab，Tislelizumab) 200 mg intravenously on day 1 of a 21-day treatment cycle until \>42 days before liver transplantation or unacceptable toxicity develops. Participants receive Lenvatinib Mesylate Capsule (Lenvima®) 8 mg orally once daily until \>7 days before liver transplantation.

Combination Product: Pembrolizumab; Drug: Sintilimab; Drug: Camrelizumab; Drug: Tislelizumab; Drug: Lenvatinib Mesylate Capsule

Interventions

intensity-modulated radiotherapy RADIATION

Neoadjuvant IMRT will be initiated at the third treatment cycle, and the dose prescription of IMRT is for planning target volume (PTV). The prescription dose to 95%PTV should be ≥50 Gy and ≤60 Gy, and been given in daily dose fractions of 2 Gy, 5 days per week. And the final prescription dose is determined according to dose constraints for organs at risk.

Also known as: IMRT

IMRT combined with PD-1 Blockade and Lenvatinib

Pembrolizumab COMBINATION_PRODUCT

Participants receive PD-1 Blockade (Pembrolizumab 200mg，Sintilimab 200mg， Camrelizumab 200mg，Tislelizumab 200mg) 100-200 mg intravenously on day 1 of a regular treatment cycle until \>42 days before liver transplantation or unacceptable toxicity develops. Participants receive Lenvatinib Mesylate Capsule (Lenvima®) 8 mg orally once daily until \>7 days before liver transplantation.

Also known as: Keytruda

IMRT combined with PD-1 Blockade and Lenvatinib; PD-1 Blockade and Lenvatinib

Sintilimab DRUG

Sintilimab is a recombinant anti-human PD-1 monoclonal antibody.

Also known as: Tyvyt

IMRT combined with PD-1 Blockade and Lenvatinib; PD-1 Blockade and Lenvatinib

Camrelizumab DRUG

Camrelizumab is a humanized anti-human PD-1 monoclonal antibody.

Also known as: AiRuiKa

IMRT combined with PD-1 Blockade and Lenvatinib; PD-1 Blockade and Lenvatinib

Tislelizumab DRUG

Tislelizumab is a recombinant anti-human PD-1 monoclonal antibody.

IMRT combined with PD-1 Blockade and Lenvatinib; PD-1 Blockade and Lenvatinib

Lenvatinib Mesylate Capsule 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

IMRT combined with PD-1 Blockade and Lenvatinib; PD-1 Blockade and 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.
• The maximum diameter of a single tumor ≤9cm. Or the number of tumors ≤3 and the maximum diameter of the largest tumors ≤5cm, and the sum of the maximum diameters of all tumors ≤9cm.
• Vp3 PVTT according to Japanese Vp classification.
• Without lymph node metastasis or extrahepatic metastasis.
• Baseline AFP≥20ng/ mL
• Has an eligibility scan (CT of the chest, triphasic CT scan and MRI of the abdomen) \<1 week before the treatment.
• 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.
• Laboratory tests within 7 days prior to Cycle 1, Day 1:
• Neutrophils ≥1.5×109/L
• Hemoglobin ≥8.5g/dL
• Platelets ≥100×109/L,
• Creatinine ≤1.5× upper limit of normal (ULN) and endogenous creatinine clearance ≥50ml/min (standard Cockcroft Gaul formula)
• Total bilirubin ≤3×ULN, ALT≤5×ULN, AST≤5×ULN, INR≤1.7
• Has controlled hepatitis B (HBV-DNA\<105IU/ml)

You may not qualify if:

• Known mixed histology (e.g. hepatocellular carcinoma plus cholangiocarcinoma) or fibrolamellar variant.
• Surgery within the past 6 months.
• Has had esophageal or gastric variceal bleeding within the last 6 months.
• Has clinically apparent ascites on physical examination.
• Has received systematic therapy such as immunotherapy, targeted therapy and chemotherapy for HCC.
• Has received TACE, HAIC, radiofrequency ablation and other local treatments in recent 2 months.
• Has received liver radiotherapy.
• Has received radiotherapy with grade 4 toxicity.
• 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.
• Has severe hypersensitivity (≥Grade 3) to monoclonal antibody.
• Has an active autoimmune disease that has required systemic treatment (skin diseases that do not require systemic treatment such as vitiligo, psoriasis; type I diabetes, and autoimmune hypothyroidism due to hormone replacement therapy are allowed).
• Patients with other active malignant tumors within 5 years before the first use of the study drug (cured localized tumors such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of prostate, carcinoma in situ of cervix and carcinoma in situ of breast are allowed).
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has known active tuberculosis within 5 years.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

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

Shanghai, 200127, China

Location

MeSH Terms

Conditions

Liver Neoplasms; Carcinoma, Hepatocellular

Interventions

Radiotherapy, Intensity-Modulated; pembrolizumab; sintilimab; camrelizumab; tislelizumab; lenvatinib

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Study Officials

• Qiang Xia, MD, Ph.D

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

  STUDY CHAIR

• Yong-rui Bai, MD

  Dept. Radiotherapy, Renji Hospital, School of Medicine, SJTU

  STUDY CHAIR

• Xiu-mei Ma, MD

  Dept. Radiotherapy, Renji Hospital, School of Medicine, SJTU

  PRINCIPAL INVESTIGATOR

• Xiao-hang Wang, MD

  Dept. Radiotherapy, Renji Hospital, School of Medicine, SJTU

  PRINCIPAL INVESTIGATOR

• 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

Qiang Xia, MD, Ph.D

CONTACT

Study Design

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

Study Record Dates

• First Submitted: April 15, 2022
• First Posted: April 21, 2022
• Study Start: May 20, 2022
• Primary Completion: December 31, 2023
• Study Completion: May 31, 2024
• Last Updated: April 27, 2022

Record last verified: 2022-04

Locations

CN (1)