Hepatocellular Carcinoma
Conditions
Interventions
Sequential radiotherapy with Donafenib and Triprolizumab:Radiation therapy will begin within two weeks of enrollment, with five sessions per week. Use intensity modulated radiation therapy (IMRT) tech
The maximum dose for both the stomach and small intestine should be less than 54Gy, V45 for the stomach should be less than 45%, and V50 for the small intestine should be less than or equal to 5%. The
The maximum dose to the spinal cord is less than 45 Gy.
Toluene sulfonic acid donafenib tablets:
Two weeks after the first radiotherapy is completed, and the researcher evaluates the patients overall
Dosage and Administration of Donafenib: The initial dose is 0.1g bid, taken twice a day, and changed to 0.2g bid after one week. It is taken orally on an empty stomach (1 hour before or 2 hours after
Until any of the following situations occur, whichever occurs first: ? The subject experiences intolerable toxic reactions that have not been relieved after dose adjustment
? The subject withdrew from the study due to imaging confirmed disease progression or other reasons.
Triprolizumab:
Administer at the same time as Donafenib, with an infusion dose of 240mg every 3 wee
Sponsors
Zhongshan Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1) Age range of 18 to 75 years old (including threshold), male or female not limited; 2) Patients with hepatocellular carcinoma clinically diagnosed as hepatocellular carcinoma or pathologically confirmed as hepatocellular carcinoma, who cannot undergo surgery; 3) There is extrahepatic metastasis, the tumor stage is CNLC IIIb, and it meets the definition of localized metastasis. Definition of limited metastasis (simulating the staging principle of small cell lung cancer "limited phase"): All lesions (intrahepatic lesions within+/-2 extrahepatic metastases, not limited to oligometastases) can be included in the radiotherapy target area, and the patient can tolerate and complete the radiotherapy plan without serious complications. Referring to traditional lymphoma staging and subtotal lymph node irradiation techniques, as well as the maximum tolerable radiation range under current advances in radiotherapy technology, extrahepatic metastases are divided into 8 regions based on characteristics such as metastasis site and number; Furthermore, the definition of localized metastatic HCC is: the total number of lesion areas (within 2 intrahepatic lesions as a single area) = 3 areas. Specifically, there are three categories: Localized metastasis above the diaphragm (zone A1) Cervical lymph node metastasis, A2 area Mediastinal lymph node metastasis, A3 area Two lung metastases within A4 area Non spinal metastases in the transverse septum within 2 locations; Localized metastasis below the diaphragm (B1 area, retroperitoneal lymph node metastasis above the hepatic and renal hilum, B2 area) Lymph node metastasis from the renal hilum to the retroperitoneum of the common iliac artery, B3 area Adrenal gland metastasis, B4 area 2 subphrenic non spinal metastases); Localized metastasis on both sides of the transverse septum, with a total of = 3 lesion areas on both sides of the transverse septum. (Note: Due to the specific neurological functions and treatment principles related to HCC brain and/or spinal metastases, this study is not included). 4) No previous history of treatment with donafenib/lenvatinib or immunotherapy, or a treatment interval of = 4 weeks from enrollment; 5) Has not undergone radiation therapy in the past; 6) HCC patients with postoperative recurrence or progression after local treatment (postoperative adjuvant therapy>6 months, and last intervention or ablation treatment completed>4 weeks) 7) At least one measurable lesion on imaging; Measurable lesion definition: Non lymphoid lesions with a longest diameter = 10 mm or lymph node lesions with a short axis = 15 mm; Previously received intervention or ablation therapy, and RECIST v1.1 evaluation indicates progression. Lesions with a longest diameter = 10 mm are considered measurable lesions; 8) Liver function Child Pugh score = 7 points; 9) The physical condition (PS) score of the Eastern Cancer Collaboration Group (ECOG) is 0-1 points; 10) Expected survival period is not less than 3 months; 11) For HBV infected individuals, if HBV-DNA is = 1000 copies/ml within 14 days before enrollment, antiviral treatment should be carried out first to reduce it to<1000 copies/ml before entering the study, and antiviral treatment and monitoring of liver function and serum HBV-DNA levels should be continued; 12) Having sufficient organ function reserves, laboratory test values within 14 days before treatment must meet the following standards: a) Blood routine examination: ?Hb=80 g/L ?ANC=1.5×109 /L
Exclusion criteria
Exclusion criteria: 1) Pathological diagnosis of hepatocellular carcinoma intrahepatic cholangiocarcinoma (HCC-ICC) mixed or fibrolamellar hepatocellular carcinoma; 2) Previously received liver transplantation; 3) Previously received systemic therapy (excluding antiviral therapy); 4) Multiple (= 3 nodules) or diffuse intrahepatic nodules, brain metastases, and spinal metastases (due to their specific neurological functions and treatment principles, this study is not included); 5) Received radiation therapy within the past 2 years; 6) Other malignant tumors within 5 years, unless the patient has received possible curative treatment and there is no evidence of the disease within 5 years, but this time requirement (that is, within 5 years) does not apply to patients with skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer carcinoma, cervical carcinoma in situ or other carcinoma in situ who have been successfully removed; 7) Having a history of severe mental illness; 8) Suffering from diseases that affect the absorption, distribution, metabolism, or clearance of research drugs (such as severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.); 9) Patients who are known or suspected to have a history of allergies to tyrosine kinase inhibitors (TKIs) or are allergic to excipients of the study drug; 10) There are uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion; 11) Has active bleeding or coagulation dysfunction, has a tendency to bleed, or is currently receiving thrombolysis, anticoagulation, or antiplatelet therapy; 12) Within the past 4 weeks, there has been a history of gastrointestinal bleeding or a clear tendency towards gastrointestinal bleeding (such as known local active ulcer lesions, fecal occult blood++, and if persistent fecal occult blood+, gastroscopy should be performed), or other conditions determined by the researcher that may cause gastrointestinal bleeding (such as severe gastric fundus/esophageal varices); 13) Within the past 6 months, there has been gastrointestinal perforation, abdominal fistula, or abdominal abscess; 14) Has experienced thrombosis or thromboembolic events within the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc; 15) Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina, or coronary artery bypass surgery within the past 6 months, congestive heart failure (NYHA classification>2), poorly controlled or pacemaker requiring arrhythmias, and uncontrolled hypertension (systolic blood pressure = 140 mmHg and/or diastolic blood pressure = 90 mmHg); 16) Active infections, including: ? AIDS virus (HIV/2 antibody) positive; Active hepatitis C (HCV antibody positive or HCV-RNA = 103 copies/ml with abnormal liver function); Active co infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); ? Active tuberculosis; Other uncontrollable active infections (CTCAE V5.0>Level 2); 17) Other significant clinical and laboratory abnormalities, which the researchers think affect the safety evaluation, such as uncontrollable diabetes, chronic kidney disease, grade II or above peripheral neuropathy (CTCAE V5.0), thyroid dysfunction, etc; 18) Pregnant or lactating women, as well as female or male patients with fertility who are unwilling or unable to take effective cont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate; | — |
Secondary
| Measure | Time frame |
|---|---|
| overall survival;Progression-free survival;disease control rate; | — |
Countries
China
Contacts
Public ContactZhifeng Wu
ZHONGSHAN HOSPITAL
Outcome results
None listed