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RECRUITING Phase 2 ClinicalTrials.gov

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

Sponsor: Shandong Cancer Hospital and Institute • ClinicalTrials.gov ID: NCT07062055

Registry updated: 2026-10-15
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Description

This single-center, prospective, single-arm Phase II clinical trial is designed to evaluate the efficacy and safety of combining hepatic artery infusion chemotherapy (HAIC, for up to 4 cycles) with iparomlimab/tuvonralimab plus bevacizumab followed by multidisciplinary team (MDT) evaluation for surgical resection or 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), and evaluate the conversion rate to surgical resectability, 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.

Interventions

  • Anti-VEGF (Drug)
    Drug: Bevacizumab (15 mg/kg, IV, every 3 weeks)
  • Immunotherapy (Drug)
    Iparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab)
  • 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
  • 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.
  • Surgical Resection (Procedure)
    Consolidative surgical resection performed on patients whose tumors are converted to resectable status, as determined by a multidisciplinary team (MDT) evaluation following the induction therapy of HAIC, bevacizumab, and iparomlimab/tuvonralimab.

Eligibility 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-2026 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 local therapy 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

Conditions

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

Locations

  • Shandong Cancer Hospital and Institute — Jinan, Shandong, China
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Official Source

Data sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

View Official Record