Phase III RCT of Radiotherapy Plus Toripalimab Versus Sorafenib in Advanced Hepatocellular Carcinoma With PVTT

NCT04709380 | Terminated Phase 3

• 1 other identifier: NCC2509
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

To explore the efficacy of radiotherapy plus toripalimab Versus standard treatment of sorafenib in advanced hepatocellular carcinoma with Portal Vein/Hepatic vein Tumor Thrombosis.

Conditions

Radiotherapy; Toripalimab; Sorafenib; Advanced Hepatocellular Carcinoma

Keywords

Radiotherpay; Anti-PD-1 antibody; Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• TTP

  Time to Progression (TTP) was defined as the duration from the date of patient recruited to the first progress at any site or the date of death.

  up to 24 months

Secondary Outcomes (3)

• ORR

  up to 24 months

• OS

  up to 24 months

• Incidence of grade 3 and above adverse events

  up to 24 months

Study Arms (2)

Radiotherapy plus Toripalimab

EXPERIMENTAL

Patients in the experimental group will be given local vein tumor thrombus/hepatic vein tumor thrombus +/- intrahepatic large lesions with hypofractionated intensity modulated radiotherapy (tumor area dose 40-60Gy/10-20f), concurrent with and followed by 240mg Q3W of toripalimab within 1 week of radiotherapy.

Other: Radiotherapy plus Toripalimab

Sorafenib

ACTIVE COMPARATOR

Patients in the control group will be treated with sorafenib (400mg, twice a day).

Drug: Sorafenib

Interventions

Radiotherapy plus Toripalimab OTHER

Intensity modulated radiotherapy has shown important role in the treatment of hepatocellular carcinoma (HCC), especially for advanced disease with portal vein tumor thrombosis (PVTT), or hepatic vein tumor thrombosis. Toripalimab is a recombinant, humanized programmed death receptor-1 (PD-1) monoclonal antibody that binds to PD-1 and prevents binding of PD-1 with programmed death ligands 1 (PD-L1) and 2 (PD-L2).

Radiotherapy plus Toripalimab

Sorafenib DRUG

Sorafenib is a multi-targeted oral drug for the treatment of cancer.Treatment of inoperable advanced renal cell carcinoma ,inoperable or distant metastatic primary hepatocellular carcinoma and so on.

Sorafenib

Eligibility Criteria

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

You may qualify if:

• Clinical or histologic diagnosis of Hepatocellular carcinoma (HCC) according to the 2019 version of liver cancer diagnosis and treatment guideline.
• Aged between 18 and 80 years.
• ECOG 0-1.
• The left volume of liver-GTV which is received less than dose of 5Gy is more than 250ml after the portal vein/hepatic vein tumor thrombosis and its connected primary main lesion is received treatment dose of 40-60Gy/10-20f.
• Patients may have a history of treatments for hepatocellular carcinoma such as TACE, radiofrequency, surgery, chemotherapy, and Chinese herbal medicine, but all patients must have not been received targeted therapy and Immunotherapy, such as anti-PD-1, anti-PD-L1 or anti-PD-L2 drug therapy.
• BCLC Stage C, HCC combined with portal vein or hepatic vein tumor thrombosis. If it is a portal vein tumor thrombosis, it must involve the left or right portal trunk at least. If it is a hepatic vein tumor thrombosis, it must involve the left or middle or right main hepatic veins at least. At the same time, eligible patients have to meet one of the following conditions. (1) There are distant metastases (except for central nervous system and meningeal metastases); (2) Both hepatic lobes are showed multiple lesions which are unable to be fully covered within the target area; (3) portal vein tumor thrombosis involved main portal trunk.
• The expected lifetime is more than 3 months.
• Child A5, A6, B7.
• Virus conditions: HBV DNA \<2000 IU/mL, if ≥ 2000 IU/mL, need to accept antiviral treatment until\<2000 IU/mL; patients with a positive HCV antibody must have a negative polymerase chain reaction (PCR) test result of HCV RNA;
• Liver function: ALT is within 2.5 times of the upper limit of normal. AST can be within 6 times of the upper limit of normal if ALT is within 1.5 times of the upper limit of normal and cardiac infarction is excluded. If ALT is 1.5 to 2.5 times the upper limit of normal, AST must be within 1.5 times the upper limit of normal.
• There is no obvious abnormality in the electrocardiography, and no obvious cardiac dysfunction.
• Renal function: CRE and BUN are within 1.5 times the upper limit of normal.
• Blood routine test: Hb≥80g/L, ANC≥1.0×10 9/L, PLT≥40×10 9/L.
• Coagulation function: no bleeding tendency.
• Willingness to voluntarily participate in the clinical trial and sign informed consent..

You may not qualify if:

• Those who are participating in other clinical trials.
• Had prior abdominal irradiation, or had prior liver transplantation.
• Patients with chronic, serious diseases such as cardiac, pulmonary, and renal disease.
• Suspected or true alcohol, drug abuse history.
• May be allergic to treatment with sorafenib or toripalimab.
• Have received immunotherapy in the past, such as anti-PD-1, anti-PD-L1, anti-PD-L2 drugs, and other drugs that stimulate or co-inhibitory T cell receptors (such as CTLA-4, OX- 40 or CD137) treatment
• Severe mental or nervous system disorders that affect informed consent and/or expression or perception of adverse events.
• Previous clinical diagnosis of hepatic encephalopathy in the past 6 months. Patients with hepatic encephalopathy which are controlled by rifaximin or lactulose are not allowed to participate in the study.
• Moderate to severe ascitic fluid with obvious symptoms.
• Concomitant secondary malignant tumors or other tumors (except superficial skin cancer, localized low-grade malignant tumors and carcinoma in situ) within 3 years before the start of the study.
• History of gastrointestinal hemorrhage within 6 months before the start of the study, or was diagnosed by ERCP/CT/DSA as a high risk of rupture and bleeding of esophageal gastric varices.
• Suffer from serious unhealed wounds, ulcers or fractures.
• Active central nervous system metastasis or cancerous meningitis.
• Active tuberculosis (TB), who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before the first medication.
• History of biliary fistula, gastrointestinal perforation, and intra-abdominal abscess within 4 weeks before the start of the study.

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

Bo Chen

Beijing, Beijing Municipality, 100021, China

Location

MeSH Terms

Interventions

Radiotherapy; toripalimab; Sorafenib

Intervention Hierarchy (Ancestors)

Therapeutics; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 14, 2021
• Study Start: March 2, 2021
• Primary Completion: December 27, 2024
• Study Completion: February 5, 2025
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)