HAIC plus iparomlimab or tuvonralimab with bevacizumab, followed by SBRT for advanced liver cancer with portal vein involvement or limited metastases
Bevacizumab Plus Iparomlimab/Tuvonralimab With Hepatic Artery Infusion Chemotherapy Followed by Stereotactic Body Radiotherapy in Patients With BCLC Stage C Hepatocellular Carcinoma With Thrombus and/or Extrahepatic Oligometastases (BITS-TO-HCC): Study Protocol of a Prospective, Single- Center, Single-Arm, Phase II Study
This trial will test whether giving hepatic artery infusion chemotherapy with an immune checkpoint antibody (iparomlimab or tuvonralimab) plus bevacizumab, followed by focused stereotactic radiation, helps people with advanced hepatocellular carcinoma that involves the portal vein or has a small number of metastases.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 54 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | Shandong Cancer Hospital and Institute Academic / other |
| Drugs / interventions | iparomlimab, tuvonralimab, bevacizumab, chimeric antigen receptor, immunotherapy, prednisone, chemotherapy |
| Locations | 1 site (Jinan, Shandong) |
| Trial ID | NCT07062055 on ClinicalTrials.gov |
What this trial studies
This is a single-center, prospective, single-arm Phase II trial enrolling patients with BCLC-C hepatocellular carcinoma complicated by portal vein tumor thrombus or extrahepatic oligometastases. Participants receive up to four cycles of hepatic artery infusion chemotherapy (HAIC) combined with iparomlimab or tuvonralimab plus bevacizumab, followed by stereotactic body radiotherapy (SBRT) to planned targets. The trial measures progression-free survival as the primary endpoint and tracks overall survival, objective response rate, disease control, local control, quality of life, and treatment-related toxicities as secondary endpoints. Eligibility requires preserved liver function (Child-Pugh A), ECOG 0–1, measurable disease, and SBRT-feasible targets.
Who should consider this trial
Good fit: Adults 18–70 years with unresectable BCLC-C hepatocellular carcinoma with portal vein tumor thrombus and/or up to five extrahepatic metastatic lesions who have Child-Pugh A liver function, ECOG 0–1, at least one measurable lesion, and lesions suitable for SBRT are the intended candidates.
Not a fit: Patients with poor liver function (Child-Pugh B/C), ECOG >1, widespread metastatic disease beyond the oligometastatic definition, inability to meet SBRT planning constraints, or significant comorbidities are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this combined locoregional and systemic approach could extend progression-free and overall survival and improve tumor control for patients with BCLC-C HCC with PVTT or limited metastases while maintaining quality of life.
How similar studies have performed: Immune checkpoint inhibitors combined with anti-VEGF agents and locoregional therapies have improved outcomes in advanced HCC in prior trials, but the specific sequence of HAIC plus dual ICI option with bevacizumab followed by SBRT is a relatively novel approach with limited direct prior evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: 1. Male or female patients aged between 18 and 70 years. 2. Unresectable HCC, BCLC Stage C according to the BCLC strategy-2025 update, with staging established via biopsy pathology and/or clinical diagnosis. 3. Child-Pugh class A without clinically significant hepatic decompensation; Eastern Cooperative Oncology Group (ECOG) performance status 0-1 4. 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 5. 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) 6. 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 * Treatment-related toxicities recovered to ≤Grade 1 (alopecia and peripheral neuropathy ≤Grade 2 allowed) 7. Laboratory and virologic requirements * Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤5 × upper limit of normal (ULN); total bilirubin ≤3 × ULN; serum albumin ≥28 g/L * Serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min * Urine dipstick protein \<2+; if baseline dipstick proteinuria is ≥2+, 24-hour urinary protein must be \<1 g * International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.5 × ULN Exclusion Criteria: 1. Histopathological exclusions * Mixed HCC subtypes: Fibrolamellar HCC or sarcomatoid HCC or cholangiocarcinoma components 2. Curative local therapy candidacy * Current candidacy for resection, liver transplant, or RFA 3. 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 4. 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 5. Hemorrhage/portal hypertension and hepatic decompensation risk * Variceal bleeding within 6 months. * Untreated or high-risk esophagogastric varices (e.g., grade ≥2 on endoscopy within 3 months) or other clinical evidence of portal hypertension with high bleeding risk per investigator. * Moderate or severe ascites * History of or active hepatic encephalopathy * History of hemoptysis (≥2.5 mL of bright red blood per episode) within 28 days before study treatment * Evidence of bleeding diathesis or significant coagulopathy * Current or recent (within 10 days before study treatment) use of aspirin (≥325 mg/day), dipyridamole, ticlopidine, clopidogrel, cilostazol, or therapeutic-dose oral/parenteral anticoagulants or thrombolytic agents 6. Allergy to any component of iparomlimab/tuvonralimab or bevacizumab 7. Comorbidities * Active autoimmune disease or a history of autoimmune or inflammatory disease that may relapse; exceptions include hypothyroidism controlled with hormone replacement only, controlled celiac disease, and skin disorders not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia) * Any condition requiring systemic corticosteroids (\>10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days before study treatment * Active or uncontrolled infection, including tuberculosis, or known HIV infection * Prior allogeneic stem cell transplantation or organ transplantation * Inadequately controlled hypertension, defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure \>90 mmHg despite optimal medical management, or a history of hypertensive crisis or hypertensive encephalopathy * History within 6 months before study treatment of myocardial infarction, unstable angina, symptomatic heart failure (New York Heart Association class ≥II), cerebrovascular accident, transient ischemic attack, pulmonary embolism, deep vein thrombosis, or other serious thromboembolic events * Major surgical procedure within 28 days before study treatment, or serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture * History within 6 months before study treatment of gastrointestinal perforation, abdominal or tracheoesophageal fistula, or intra-abdominal abscess
Where this trial is running
Jinan, Shandong
- Shandong Cancer Hospital and Institute — Jinan, Shandong, China (Recruiting)
Study contacts
- Principal investigator: Jinbo Yue, Doctor — Shandong Cancer Hospital and Institute
- Study coordinator: Jinbo Yue, doctor
- Email: jbyue@sdfmu.edu.cn
- Phone: 0531-67626442
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.