A Phase 2 interventional study of Anti-VEGF and Immunotherapy in Hepatocellular Carcinoma, Portal Vein Tumor Thrombus and Oligometastases, sponsored by Shandong Cancer Hospital and Institute. Recruiting at 1 site in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-10-15.
Sponsored by Shandong Cancer Hospital and Institute · Phase 2, Interventional, and Treatment
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.
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.
3,648 studies on the registry are indexed under Carcinoma, Hepatocellular; 1,061 are open to participants now.
This study's planned enrollment of 54 is close to the median of 54 across 2,618 interventional studies indexed under Carcinoma, Hepatocellular.
Browse Carcinoma, Hepatocellular studies →Shandong Cancer Hospital and Institute is the lead sponsor of 105 studies on the registry; 38 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
burden and local therapy eligibility
Prognosis \&
Prior therapy
Laboratory and virologic requirements
Exclusion Criteria:
Histopathological exclusions
Curative local therapy candidacy
RT infeasibility
Prior systemic therapies
Hemorrhage/portal hypertension and hepatic decompensation risk
Comorbidities
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Anti-VEGF · Drug: Immunotherapy · Radiation: Local Therapy · Procedure: hepatic arterial infusion chemotherapy (HAIC) · Procedure: Surgical Resection
Drug: Bevacizumab (15 mg/kg, IV, every 3 weeks)
Iparomlimab/tuvonralimab (7.5 mg/kg, IV, every 3 weeks, administered sequentially after bevacizumab)
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
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.
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.
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.
Time frame: Two years
Overall Survival (OS)
Time from initiation of treatment to death from any cause.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Two years
Plan to share: No
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.
Contact study teamGet an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Bevacizumab
Shandong Cancer Hospital and Institute →