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

  • STATUS
    Recruiting
  • days left to enroll
    88
  • participants needed
    85
  • sponsor
    Chinese Academy of Medical Sciences
Updated on 18 March 2021

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.

Description

This is an single-center, open, randomized study, which is going to enroll patients filtered to meet the standard of advanced hepatocellular carcinoma, in a 2: 1-proportional randomly assigned to the test group and control group. 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 started. Patients in the control group will be treated with sorafenib (400mg, twice a day).

Details
Condition Radiation Oncology, Radiotherapy, radiotherapeutic, Sorafenib, Advanced Hepatocellular Carcinoma, Toripalimab
Treatment Sorafenib, Radiotherapy plus Toripalimab
Clinical Study IdentifierNCT04709380
SponsorChinese Academy of Medical Sciences
Last Modified on18 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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
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: Hb80g/L, ANC1.010 9/L, PLT4010 9/L
Coagulation function: no bleeding tendency
Willingness to voluntarily participate in the clinical trial and sign informed consent

Exclusion Criteria

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
History of unstable angina, myocardial infarction, coronary artery bypass grafting, congestive heart failure, cerebrovascular accident (including transient ischemic attack, pulmonary embolism) within 3 months before the start of the study
NCI-CTCAE v.4 grade 2 cardiac arrhythmia, atrial fibrillation, or QT interval prolongation of any NCI-CTCAE v.4 grade (male > 450ms, female > 470ms)
Uncontrollable hypertension treated with best antihypertensive drugs (> 150/90mmHg after rational medication)
History of HIV infection
Females who are pregnant or breastfeeding
Live vaccines were vaccinated within 30 days before the first dose of study drug. Live vaccines include but are not limited to the following: measles, mumps, rubella, varicella/shingles (chickenpox), yellow fever, rabies, BCG (BCG) and typhoid vaccines. Since seasonal influenza vaccines for injection are usually inactivated virus vaccines, their use is allowed; however, intranasal influenza vaccines (for example, FluMist) are live attenuated vaccines, so they are not allowed
Have an active autoimmune disease that requires systemic treatment in the past 2 years (for example, immunomodulatory drugs, corticosteroids, or immunosuppressive drugs. Autoimmune diseases such as autoimmune hepatitis, interstitial pneumonia, uveal Inflammation, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid syndrome related vascular thrombosis, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barr syndrome, multiple sclerosis, vasculitis, Glomerulonephritis, etc., hyperthyroidism or hypothyroidism, asthma that requires bronchodilator treatment, etc.). Replacement therapy (for example, thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic therapy and is allowed
Combined with medical contraindications that cannot accept any contrast-enhanced imaging examinations (CT or MRI)
Severely allergic to research intervention and/or any of its excipients (Grade 3)
Uncontrolled metabolic disorders or other non-malignant tumor organs or systemic diseases or cancer secondary reactions, which can lead to higher medical risks and/or uncertainty in survival evaluation
Patients who have received allogeneic tissue/solid organ transplantation
Patients with other acute or chronic diseases, mental illnesses, or abnormal laboratory test values that may cause the following results: increase the risk related to study participation or study drug administration, or interfere with the interpretation of the study results, and the patients shall be treated according to the judgment of the investigator classified as not eligible to participate in this study
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