Radiotherapy + Sintilimab + Bevacizumab Biosimilar for uHCC With PVTT

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma Non-resectable
• Intervention / Treatment: Combination product: radiotherapy combined with sintilimab and bevacizumab biosimilar

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.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jia Luo, Professor; Phone Number: 86-0731-89762031; Email: luojia@hnca.org.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Hunan Cancer Hospital
      • Contact: Jia Luo, Professor; Phone Number: +86-0731-89762031; Email: luojia@hnca.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: treatment group; radiotherapy combined with sintilimab and bevacizumab biosimilar

Combination product: radiotherapy combined with sintilimab and bevacizumab biosimilar; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response rate	assessed according to the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1, undergoing enhanced CT/MRI	up to 2 years from enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	the time from enrollment until death or the last follow-up	up to 2 years from enrollment
number of participants with treatment-related adverse events	number of participants with treatment-related adverse events as assessed by CTCAE v4.0	up to 2 years from enrollment
Objective Response rate, assessed according to the modified Response Evaluation Criteria	assessed according to the modified Response Evaluation Criteria in Solid Tumors Version 1.1, undergoing enhanced CT/MRI	up to 2 years from enrollment

Collaborators and Investigators

• Sponsor: Yongchang Zhang
• Investigators: Principal Investigator: Jia Luo, Professor, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: August 27, 2022
• First Submitted That Met QC Criteria: September 6, 2022
• First Posted (Actual): September 7, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 6, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: uHCC with PVTT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No