Hepatocellular CarcinomaPhase 2NCT07062055
BITS-TO-HCC Study: HAIC+Iparomlimab/Tuvonralimab + Bevacizumab + Surgery/SBRT for BCLC-C HCC With PVTT and/or Oligometastases
A Phase 2 study testing Anti-VEGF, Immunotherapy and Local Therapy in people with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus, run by Shandong Cancer Hospital and Institute at 1 site in China.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hepatocellular Carcinoma, Portal Vein Tumor Thrombus, Oligometastases
- What is being tested?
- Anti-VEGF, Immunotherapy and Local Therapy
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteChina
- Study dates
- 25 Jul 2025to 25 Jul 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients aged between 18 and 70 years.
- Unresectable HCC, BCLC Stage C according to the BCLC strategy-2026 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 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
Show all 21Show fewer
- 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
- Treatment-related toxicities recovered to ≤Grade 1 (alopecia and peripheral neuropathy ≤Grade 2 allowed)
- 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
Who cannot join
- Histopathological exclusions
- 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
Show all 32Show fewer
- 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.
- 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
- Allergy to any component of iparomlimab/tuvonralimab or bevacizumab
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Shandong Cancer Hospital and Institute
Jinan, Shandong
Jinbo Yue, doctor, 0531-67626442, jbyue@sdfmu.edu.cn
Jinbo Yue, Doctor, jbyue@sdfmu.edu.cn
About this study
Official title: Bevacizumab Plus Iparomlimab/Tuvonralimab With Hepatic Artery Infusion Chemotherapy Followed by Surgical Resection or 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 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.
Read the 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. By achieving substantial tumor debulking, this intensive locoregional-systemic approach aims to convert initially unresectable disease into resectable status for select patients. Furthermore, for 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 HAIC with dual ICIs (iparomlimab/tuvonralimab) and bevacizumab, followed by a multidisciplinary team (MDT) evaluation for subsequent surgical resection or consolidative SBRT, will act synergistically to improve progression-free survival (PFS) and conversion resectability rates 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
- Being tested
- Anti-VEGF, Immunotherapy, Local Therapy, hepatic arterial infusion chemotherapy (HAIC), Surgical Resection
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-VEGFDrug
Drug: Bevacizumab (15 mg/kg, IV, every 3 weeks)
ImmunotherapyDrug
Iparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab)
Local TherapyRadiation
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 or surgery
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 ResectionProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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) Procedure: Following induction therapy, patients will undergo a multidisciplinary team (MDT) evaluation. Patients who meet the criteria for resectability will undergo Surgical Resection.
Radiation: For patients deemed unresectable, 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 will be administered. Receives: Drug: Anti-VEGF; Drug: Immunotherapy; Radiation: Local Therapy; Procedure: hepatic arterial infusion chemotherapy (HAIC); Procedure: Surgical Resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Two years
Secondary outcomes (7)
Overall Survival (OS)
Time from initiation of treatment to death from any cause.
Measured: Five years
objective response rate (ORR)
The proportion of patients whose tumor size decreases (partial response) or disappears (complete response) after induction therapy and/or consolidative local therapy (surgery or SBRT) based on RECIST 1.1.
Measured: Two years
Disease Control Rate (DCR)
The proportion of patients whose tumor size decreases (partial response), disappears (complete response), or is stable after induction therapy and/or consolidative local therapy (surgery or SBRT) based on RECIST 1.1.
Measured: Two years
Local control rate (LCR)
The proportion of treated lesions without in-field local progression within the irradiated/target volume at prespecified time points (e.g., 6 and 12 months) per RECIST 1.1
Measured: Two years
Conversion to Resectability Rate
The proportion of initially unresectable patients who are successfully converted to a resectable status and undergo surgical resection following induction therapy, as determined by a multidisciplinary team (MDT) evaluation.
Measured: Two years
Incidence of Treatment-related adverse events
Treatment-related adverse events will be assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Specific examples of expected toxicities include, but are not limited to:
Gastrointestinal disorders: Abdominal distension (visible or palpable enlargement of the abdomen); Abdominal pain; Belching; Subjective sensation of gastric bloating or fullness; Nausea (with or without retching or urge to vomit); Vomiting; Dyspepsia (characterized by burning sensation, bloating, nausea, or discomfort); Constipation; Diarrhea; Dysphagia (difficulty in swallowing); Upper gastrointestinal bleeding General disorders and administration site conditions: Fatigue; Pain, such as radiation-associated pain at sites of bone metastases or liver region pain Respiratory disorders: Dyspnea (shortness of breath); Radiation pneumonitis Skin and subcutaneous tissue disorders: Radiation dermatitis.
Measured: Five years
Change in Quality of Life Assessed by EORTC QLQ-C30 Questionnaire
Quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Changes from baseline to follow-up time points will be analyzed across multiple domains including physical, emotional, and social functioning.
Measured: Two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2025
- Study start25 Jul 2025
- Primary completion25 Jul 2028 (estimated)
- Study completion25 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong Cancer Hospital and Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinbo Yue, Shandong Cancer Hospital and Institute
- Investigators
- Jinbo Yue, Doctor, Principal investigator, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07062055
- Sponsor's protocol ID
- SDZLEC2025-152-06
- Status last verified
- Oct 2026
- First submitted
- 24 Jun 2025
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liu Y, Wang H, Zhu K, Jiang S, Shi F, Feng R, Dou X, Xu L, Gong Z, Wang S, Wang C, Wang P, Zhang X, Yue J. 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. Ther Adv Med Oncol. 2026 Jul 24;18:17588359261470693. doi: 10.1177/17588359261470693. eCollection 2026.
PubMed 42502358
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bevacizumab Plus Iparomlimab/Tuvonralimab With Hepatic Artery Infusion Chemotherapy Followed by Surgical Resection or 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
- ClinicalTrials.gov ID
- NCT07062055
- Acronym / sponsor ID
- SDZLEC2025-152-06
- Conditions
- Hepatocellular Carcinoma, Portal Vein Tumor Thrombus, Oligometastases, Radiotherapy, Immunotherapy, Hepatic Artery Infusion Chemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 54 participants (estimated)
- Lead sponsor
- Shandong Cancer Hospital and InstituteUniversity, hospital or other
- Study start
- 25 Jul 2025 (actual)
- Primary completion
- 25 Jul 2028 (estimated)
- Study completion
- 25 Jul 2029 (estimated)
- First posted
- 14 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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. By achieving substantial tumor debulking, this intensive locoregional-systemic approach aims to convert initially unresectable disease into resectable status for select patients. Furthermore, for 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 HAIC with dual ICIs (iparomlimab/tuvonralimab) and bevacizumab, followed by a multidisciplinary team (MDT) evaluation for subsequent surgical resection or consolidative SBRT, will act synergistically to improve progression-free survival (PFS) and conversion resectability rates in patients with BCLC stage C HCC complicated by PVTT and/or extrahepatic oligometastases, while maintaining an acceptable safety profile.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Anti-VEGF, Drug: Immunotherapy, Radiation: Local Therapy, Procedure: hepatic arterial infusion chemotherapy (HAIC), Procedure: Surgical ResectionHepatic 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) Procedure: Following induction therapy, patients will undergo a multidisciplinary team (MDT) evaluation. Patients who meet the criteria for resectability will undergo Surgical Resection. Radiation: For patients deemed unresectable, 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 will be administered. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Male or female patients aged between 18 and 70 years.
- Unresectable HCC, BCLC Stage C according to the BCLC strategy-2026 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 local therapy eligibility
- Prognosis \& measurable disease
Key exclusion criteria (32 listed)
- Histopathological exclusions
- Curative local therapy candidacy
- RT infeasibility
- Prior systemic therapies
- Hemorrhage/portal hypertension and hepatic decompensation risk
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Anti-VEGFDrug: Bevacizumab (15 mg/kg, IV, every 3 weeks) | Drug | Treatment |
| ImmunotherapyIparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab) | Drug | Treatment |
| Local TherapyStereotactic 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 | Radiation | Treatment |
| 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. | Procedure or surgery | Treatment |
| Surgical ResectionConsolidative 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. | Procedure or surgery | Treatment |
Primary outcome
Progression-free survival (PFS)
Time frame: Two years
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.
7 secondary outcomes
Overall Survival (OS)
Time frame: Five years
objective response rate (ORR)
Time frame: Two years
Disease Control Rate (DCR)
Time frame: Two years
Local control rate (LCR)
Time frame: Two years
Conversion to Resectability Rate
Time frame: Two years
Incidence of Treatment-related adverse events
Time frame: Five years
Change in Quality of Life Assessed by EORTC QLQ-C30 Questionnaire
Time frame: Two years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Derived from this study: PubMed 42502358Liu Y, Wang H, Zhu K, Jiang S, Shi F, Feng R, Dou X, Xu L, Gong Z, Wang S, Wang C, Wang P, Zhang X, Yue J. 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. Ther Adv Med Oncol. 2026 Jul 24;18:17588359261470693. doi: 10.1177/17588359261470693. eCollection 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jinbo Yue, Doctor principal investigator
Shandong Cancer Hospital and Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Anti-VEGF, Immunotherapy and Local Therapy in people with Hepatocellular Carcinoma and Portal Vein Tumor Thrombus, run by Shandong Cancer Hospital and Institute at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jinbo Yue, doctor (0531-67626442, jbyue@sdfmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: Two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07062055, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.