Clinical trial NCT05530785: Radiotherapy + Sintilimab + Bevacizumab Biosimilar for uHCC With PVTT
Official title: An Exploratory Clinical Study of Radiotherapy Combined With Sintilimab Plus Bevacizumab Biosimilar in the Treatment of Unresectable Hepatocellular Carcinoma (uHCC) With Portal Vein Tumor Thrombus (PVTT)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hepatocellular Carcinoma Non-resectable
Lead sponsor: Hunan Province Tumor Hospital
Sponsor class: OTHER
First posted: 2022-09-07
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study was a prospective, single-arm, single-center, phase II exploratory clinical study. To investigate the efficacy and safety of radiotherapy combined with sintilimab and bevacizumab biosimilar in the treatment of unresectable hepatocellular carcinoma with portal vein tumor thrombus.

Detailed description: After signing informed consent, patients received sintilimab 200 mg intravenously on the first day of each cycle, Q3W; Bevacizumab biosimilar 7.5mg/kg was administered intravenously on the first day of each cycle, Q3W; Concurrent radiotherapy (single dose 3-8Gy, times 3-10, total dose 20-50Gy; The duration of radiotherapy was completed between the first administration of sintilimab and the second administration of bevacizumab, but it should be noted that the interval between before and after the administration of sintilimab and bevacizumab was at least 3 days.

Patients will be performed enhanced CT/MRI every 2 months, to access the efficiency according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, undergoing enhanced CT/MRI. The overall survival (OS) was calculated as the time from enrollment until death or the last follow-up. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 to access the safety.

Eligibility criteria: Inclusion Criteria:

1. Hepatocellular carcinoma confirmed by histology/cytology, or patients with cirrhosis and meet the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria for HCC
2. Child-pugh grade A or B (≤7 points)
3. A score of 0-1 according to the Eastern Cooperative Oncology Group Physical Status Score (ECOG PS score);
4. Barcelona stage C; Inamicable for radical surgical resection or refusal of surgery without extra-hepatic metastases; Portal vein tumor thrombus (PVTT) was diagnosed by enhanced CT or enhanced MRI (type VP1 to VP3).
5. Had not received systemic therapy or radiotherapy before; Or disease progression after surgical resection or local treatment (without radiotherapy);
6. At least one measurable or evaluable lesion according to the response evaluation criteria for solid tumors, version 1.1 (RECIST V1.1); Or measurable lesions that had clearly progressed after local treatment (based on RECIST V1.1 criteria).
7. Patients with liver lesions and/or portal vein tumor thrombus lesions were treated with radiotherapy

Exclusion Criteria:

1. Previous histological/cytological diagnosis included fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, and other components.
2. The area to be treated had been previously treated with radiotherapy
3. Patients with extrahepatic metastases
4. Patients with tumor thrombus invasion into the superior mesenteric vein
5. Patients with inferior vena cava tumor thrombus.
6. Central nervous system metastases were present.
7. A history of hepatic encephalopathy, or a history of liver transplantation.
8. There are clinical symptoms of pleural effusion, ascites, or pericardial effusion that require drainage.
9. Patients with acute or chronic active hepatitis B or C with hepatitis B virus (HBV) DNA\>2000IU/ml or 10\^4 Copies/ml; Hepatitis C virus (HCV)RNA\> 10\^3 Copies/ml; Hepatitis B surface antigen (HbsAg) and anti-HCV antibody were both positive.
10. History of allergy to active ingredients and/or excipients of anti-PD-1 mab and anti-VEFG mab.
11. Other malignancies, except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix, were present within 5 years.
12. Bleeding events from esophageal or gastric fundus varices due to portal hypertension had occurred within the previous 6 months. Severe (G3) varicose veins were known to have been present on endoscopy within 3 months before the first dose. There was evidence of portal hypertension (including splenomegaly on imaging) and a high risk of bleeding as assessed by the investigator.

Primary outcomes:
measure: Objective Response rate
timeFrame: up to 2 years from enrollment
Secondary outcomes:
measure: Objective Response rate, assessed according to the modified Response Evaluation Criteria
timeFrame: up to 2 years from enrollment
measure: overall survival
timeFrame: up to 2 years from enrollment
measure: number of participants with treatment-related adverse events
timeFrame: up to 2 years from enrollment
Other outcomes:
Locations:
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
Study officials:
affiliation: Hunan Cancer Hospital
name: Jia Luo, Professor
role: PRINCIPAL_INVESTIGATOR
References: