Trials / Recruiting
RecruitingNCT07062055
BITS-TO-HCC Study: HAIC+Iparomlimab/Tuvonralimab + Bevacizumab + SBRT for BCLC-C HCC With PVTT and/or Oligometastases
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, Multicenter, Single-Arm, Phase II Study
- Status
- Recruiting
- Phase
- Phase 2
- Study type
- Interventional
- Enrollment
- 54 (estimated)
- Sponsor
- Shandong Cancer Hospital and Institute · Academic / Other
- Sex
- All
- Age
- 18 Years – 70 Years
- Healthy volunteers
- Not accepted
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.
Detailed description
In recent years, first-line systemic treatment of advanced hepatocellular carcinoma (HCC) has shifted toward immunotherapy-based combinations, particularly regimens pairing immune checkpoint inhibitors (ICIs) with vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR)-targeted antiangiogenic agents, which have become the preferred options in major clinical guidelines. Nevertheless, a substantial proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage C disease complicated by portal vein tumor thrombus (PVTT) and/or extrahepatic oligometastases remain ineligible for resection despite conversion-oriented systemic or locoregional therapy. Even when hepatectomy is attempted in this subset, candidates are highly selected and the overall benefit appears limited. Accordingly, major contemporary guidelines adopt a cautious stance on resection in the presence of PVTT, which remains controversial in some respects. In parallel, recent phase III trials evaluating transarterial chemoembolization (TACE) in combination with immunotherapy and anti-VEGF agents have supported the emergence of a locoregional-systemic treatment paradigm for unresectable, non-metastatic HCC. However, patients with BCLC stage C HCC with PVTT and/or extrahepatic oligometastases were generally under-represented or excluded, leaving the applicability of these regimens to this population uncertain. By contrast, stereotactic body radiotherapy (SBRT) delivered with ablative intent can achieve high local control under stringent dose-volume constraints. Furthermore, radiotherapy (RT) may induce immunogenic cell death and reshape the tumor microenvironment, thereby amplifying systemic immune responses and providing a biological rationale for combination with ICIs and anti-VEGF therapy. Iparomlimab/tuvonralimab, a novel bispecific antibody designed to target both programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), offers a promising approach to augment T-cell activation and strengthen antitumor immunity beyond what is achievable with single-agent ICIs. When combined with bevacizumab, which blocks VEGF signaling to normalize tumor vasculature, improves the tumor microenvironment, and promotes immune-cell infiltration, this dual strategy could significantly enhance treatment efficacy. Hepatic artery infusion chemotherapy (HAIC) concentrates cytotoxic exposure within the liver and induces rapid cytoreduction, facilitating downstaging in advanced HCC. For the HAIC component, we selected an FOHAIC-1-based HAIC-FO regimen because it is among the best-validated HAIC backbones in advanced HCC and significantly improved overall survival (OS) versus sorafenib in the randomized phase III FOHAIC-1 trial. This oxaliplatin-fluorouracil-leucovorin HAIC backbone has also been explored in combination studies with immunotherapy and anti-angiogenic therapy, supporting its feasibility within multimodal treatment strategies. Among patients who remain ineligible for resection despite modern conversion strategies, HAIC-mediated debulking can help render intrahepatic disease dosimetrically amenable to local ablation with SBRT. Building on this rationale, we hypothesise that a sequential regimen combining dual ICIs (iparomlimab/tuvonralimab) and bevacizumab with HAIC, followed by consolidative SBRT, will act synergistically to improve progression-free survival (PFS) in patients with BCLC stage C HCC complicated by PVTT and/or extrahepatic oligometastases, while maintaining an acceptable safety profile.
Conditions
- Hepatocellular Carcinoma
- Portal Vein Tumor Thrombus
- Oligometastases
- Radiotherapy
- Immunotherapy
- Hepatic Artery Infusion Chemotherapy
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Anti-VEGF | Drug: Bevacizumab (15 mg/kg, IV, every 3 weeks) |
| DRUG | Immunotherapy | Iparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab) |
| RADIATION | Local Therapy | 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 |
| PROCEDURE | hepatic arterial infusion chemotherapy (HAIC) | 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. |
Timeline
- Start date
- 2025-07-25
- Primary completion
- 2028-07-25
- Completion
- 2029-07-25
- First posted
- 2025-07-14
- Last updated
- 2026-04-01
Locations
1 site across 1 country: China
Source: ClinicalTrials.gov record NCT07062055. Inclusion in this directory is not an endorsement.