BITS-TO-HCC Study: HAIC+Iparomlimab/Tuvonralimab + Bevacizumab + SBRT for BCLC-C HCC With PVTT and/or Oligometastases

NCT07062055 | Recruiting Phase 2

• 1 other identifier: SDZLEC2025-152-02
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, prospective, single-arm Phase II clinical trial is designed to evaluate the efficacy and safety of combining bevacizumab plus iparomlimab/tuvonralimab with hepatic artery infusion chemotherapy (HAIC) followed by stereotactic body radiotherapy (SBRT) in patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC) who present with portal vein tumor thrombus (PVTT) or extrahepatic oligometastatic disease. The study aims to determine whether this combination strategy can prolong progression-free survival (PFS), while also improving overall survival (OS), objective response rate (ORR), disease control rate (DCR), and local control rate (LCR), as well as maintaining quality of life (QoL). In addition, the trial will systematically evaluate the safety profile and treatment-related toxicities associated with this regimen.

Conditions

Hepatocellular Carcinoma; Portal Vein Tumor Thrombus; Oligometastases; Radiotherapy; Immunotherapy; Hepatic Artery Infusion Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  The time between enrollment and disease progression or death for patients in the intent-to-treat population, whichever occurred first; for those who did not progress at the time of withdrawal from the study or whose time to disease progression was not recorded, the date of the last visit was used as the endpoint date.

  Two years

Secondary Outcomes (6)

• Overall Survival (OS)

  Five years

• objective response rate (ORR)

  Two years

• Disease Control Rate (DCR)

  Two years

• Local control rate (LCR)

  Two years

• Incidence of Treatment-related adverse events

  Five years

Study Arms (1)

Treatment

EXPERIMENTAL

Hepatic artery infusion chemotherapy (HAIC): On Day 1 of each cycle, initiated via a hepatic arterial catheter or pump and completed over 2-3 days, as follows: oxaliplatin 130 mg/m², leucovorin 200 mg/m², fluorouracil 400 mg/m² as a bolus, followed by fluorouracil 2,400 mg/m² by continuous infusion over 46 h (every 3 weeks for up to four cycles) Drug: Bevacizumab (15 mg/kg, IV, every 3 weeks) Drug: Iparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab) Radiation: Stereotactic Body Radiotherapy (SBRT), total dose of 25-40 Gy in 5 fractions over 1-2 weeks, targeting intrahepatic tumors, portal vein tumor, and/or limited extrahepatic oligometastatic lesions

Drug: Anti-VEGF; Drug: Immunotherapy; Radiation: Local Therapy; Procedure: hepatic arterial infusion chemotherapy (HAIC)

Interventions

Anti-VEGF DRUG

Drug: Bevacizumab (15 mg/kg, IV, every 3 weeks)

Treatment

Immunotherapy DRUG

Iparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab)

Treatment

Local Therapy RADIATION

Stereotactic Body Radiotherapy (SBRT), total dose of 25-40 Gy in 5 fractions over 1-2 weeks, targeting intrahepatic tumors, portal vein tumor, and/or limited extrahepatic oligometastatic lesions

Treatment

hepatic arterial infusion chemotherapy (HAIC) PROCEDURE

On Day 1 of each cycle, HAIC using the HAIC-FO regimen will be initiated via a hepatic arterial catheter or pump and completed over 2-3 days, as follows: oxaliplatin 130 mg/m², leucovorin 200 mg/m², fluorouracil 400 mg/m² as a bolus, followed by fluorouracil 2,400 mg/m² by continuous infusion over 46 h. HAIC may be administered every 3 weeks for up to four cycles.

Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients aged between 18 and 70 years.
• Unresectable HCC, BCLC Stage C according to the BCLC strategy-2025 update, with staging established via biopsy pathology and/or clinical diagnosis.
• Child-Pugh class A without clinically significant hepatic decompensation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Metastatic burden and SBRT eligibility
• Extrahepatic oligometastatic disease defined as ≤3 involved organs with ≤5 total metastatic lesions
• All intended intrahepatic and/or extrahepatic SBRT targets must satisfy protocol-specified target-coverage, liver reserve, and organ-at-risk (OAR) constraints within a composite 5-fraction plan
• Prognosis \& measurable disease
• Life expectancy ≥3 months
• ≥1 measurable lesion (per RECIST 1.1):
• Tumor: ≥10 mm (CT long axis)
• Lymph node: ≥15 mm (CT short axis)
• Prior therapy
• Prior locoregional therapy permitted：radiofrequency ablation (RFA), TACE, or HAIC, provided that:
• Documented radiographic progression or intolerance after the prior therapy
• Washout ≥28 days

You may not qualify if:

• Mixed HCC subtypes: Fibrolamellar HCC or sarcomatoid HCC or cholangiocarcinoma components
• Curative local therapy candidacy
• Current candidacy for resection, liver transplant, or RFA
• RT infeasibility
• Prior radioembolization
• Single liver tumor ≥15 cm or total intrahepatic tumor diameter ≥20 cm
• more than 5 discrete intrahepatic parenchymal foci are present
• direct tumor extension into the stomach, duodenum, small bowel, or large bowel
• measurable common or main-branch biliary duct involvement
• Prior liver radiotherapy that would result in excessive overlap with the planned treatment fields
• Prior systemic therapies
• Received targeted-immunotherapy for HCC (e.g., PD-(L)1 inhibitors + tyrosine kinase inhibitors (TKIs))
• Prior immunotherapy: anti-PD-(L)1/CTLA-4 or chimeric antigen receptor T-cell therapy
• Hemorrhage/portal hypertension and hepatic decompensation risk
• Variceal bleeding within 6 months.

Sponsors & Collaborators

• Shandong Cancer Hospital and Institute: lead

Study Sites (1)

Shandong Cancer Hospital and Institute

Jinan, Shandong, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Immunotherapy; Hyperthermia, Induced

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Study Officials

• Jinbo Yue, Doctor

  Shandong Cancer Hospital and Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinbo Yue, doctor

CONTACT

0531-67626442; jbyue@sdfmu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Radiation Oncology Department

Study Record Dates

• First Submitted: June 24, 2025
• First Posted: July 14, 2025
• Study Start: July 25, 2025
• Primary Completion (Estimated): July 25, 2028
• Study Completion (Estimated): July 25, 2029
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)