NIPH Clinical Trials Search

Multicenter, Single-arm trial of single tremelimumab regular interval durvalumab followed by hepatectomy for initially unresectable hepatocellular carcinoma

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	Hepatocellular Carcinoma
Date of first enrollment	14/07/2025
Target sample size	50
Countries of recruitment
Study type	Interventional
Intervention(s)	To assess the safety of multimodal treatment of unresectable hepatocellular carcinoma with durvalumab plus tremelimumab and surgical resection.

Outcome(s)

Primary Outcome

Incidence of postoperative complications of the Clavien-Dindo grade 3 or higher in patients receiving hepatectomy

Secondary Outcome

1) Surgical resection rate in enrolled patients 2) Incidence of Posthepatectomy Liver Failure: PHLF in patients receiving hepatectomy 3) Surgical resection rate with effective protocol treatment in enrolled patients 4) Progression-Free Survival (PFS; mRECIST) in enrolled patients 5) Progression-free survival (PFS; RECIST ver1.1) in enrolled patients 6) Overall Survival: OS in enrolled patients 7) Overall Response Rate (ORR; RECIST ver1.1 and mRECIST) in enrolled patients 8) Gross curative resection rate in patients receiving hepatectomy 9) ICG 15-minute retention rate after drug treatment in enrolled patients

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	Not applicable
Gender	Both
Include criteria	1.Body weight > 30 kg 2.At least 12 weeks of life expectancy at the time of enrollment 3.Unresectable hepatocellular carcinoma without history of previous systemic therapy with drugs (sorafenib, lenvatinib, and immunotherapy) for hepatocellular carcinoma 4.At least one target lesion based on RECIST ver1.1 criteria 5.Age >18 years at time of study entry 6.Eastern Cooperative Oncology Group (ECOG)>><<World Health Organization (WHO) performance status of 0 or 1 7.Adequate normal organ and marrow function within 14 days prior to enrollment as defined below: Hemoglobin >-9.0 g/dL Absolute neutrophil count (ANC >-1000/uL) Platelet count >-75000 /uL Serum bilirubin <-2.0 x institutional upper limit of normal (ULN). <<This will not apply to patients with confirmed Gilbert s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.>> AST (SGOT)/ALT (SGPT) <-5 x institutional upper limit of normal Albumin >-2.8g/dL International normalized ratio (INR) <-1.6 Serum creatinine <- 1.5 times the upper limit set at each medical institution Measured creatinine clearance (CL) >40 mL/min or calculated creatinine clearance (CL) >40 mL/min as determined by Cockcroft-Gault formula (Cockcroft and Gault 1976) using actual body weight or 24-hour urine creatinine clearance: 8.Child Pugh score 5-6 within 14 days prior to enrollment 9.No other active malignancy 10.Capable of giving signed informed consent which includes compliance with the requirements and. restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization. For patients aged <20 years and enrolling in Japan, a written informed consent should be obtained from the patient and his or her legally acceptable representative. 11.Patient is willing and able to comply with the protocol for the duration of the study including undergoing. treatment and scheduled visits and examinations including follow up. 12.The tumor condition is determined to be unresectable hepatocellular carcinoma as classified in the following categories*1: A, B, C, D, and E. A) [Intrahepatic vascular invasion] Intrahepatic tumors are classified as Vv2-3, Vp2-4, and B2-4. No extrahepatic tumors are observed. Vv2: Invasions and tumor thrombus in the main right and left hepatic veins, the inferior right hepatic vein, or the short hepatic vein Vv3: Invasions and tumor thrombus in the inferior vena cava Vp2: Invasions and tumor thrombus in secondary branches of portal vein Vp3: Invasions and tumor thrombus in primary branches of portal vein Vp4: Invasions and tumor thrombus in the main portal vein trunk and contralateral portal branches B2: Invasions and tumor thrombus in secondary branches of bile ducts B3: Invasions and tumor thrombus in the primary bile duct branches B4: Invasions and tumor thrombus in the common bile duct B)[Synchronous extrahepatic metastases] Intrahepatic tumors are resectable without gross vascular invasion and extrahepatic tumors which are localized to a single organ metastasis such as distant organ metastases, peritoneal metastases, lymph node metastases, and tumor seeding along the puncture route are present. *2 C)[Intrahepatic vascular invasion and synchronous extrahepatic metastasis] same as mentioned in B. Intrahepatic tumors are Vv2-3, Vp2-4, and B2-4 and are diagnosed as synchronous extrahepatic metastasis*2. D)[Gross tumor remnant] Resection of all intrahepatic tumors is difficult but expected to improve survival benefits or quality of life*3. E)[Metachronous extrahepatic metastasis] Intrahepatic tumor is absent or controllable. Diagnosed as extrahepatic metastasis*4. *1 Tumor conditions A-E have a poor prognosis and are oncologically unresectable. It is also classified as unresectable in the BCLC guidelines (Appendix 3), which are frequently used worldwide. In the past, surgical resection of hepatocellular carcinoma with extrahepatic metastasis or vascular invasion has been performed in selected centers with a large number of resected cases, but the long-term prognosis is poorer than that of patients without these conditions. *2 Localized to a single organ metastasis. Adrenal gland: no bilateral metastasis. Lymph node: only intra-abdominal metastasis. The maximum number is 2. Lung: the maximum number is 5. Peritoneal metastases: the maximum number is 5. Puncture route recurrence: the maximum number of 1. If extrahepatic metastases are difficult to diagnose, PET or other tests deemed necessary will be performed, and each medical institution will make a comprehensive judgement of eligibility for the study. Bone metastasis is excluded. *3 For example, in cases in which intrahepatic tumors present heterogenous responses to therapies, tumors which are not controlled with drug therapy are resected. *4 Patients with bone metastases are excluded, otherwise the same as *2.
Exclude criteria	1.Patients who have untreated or poorly treated esophageal varices and/or varices with or at high risk of bleeding, or a history of bleeding due to esophageal varices and/or varices within 180 days prior to enrollment. (Esophagogastroduodenoscopy (EGD) must be performed prior to enrollment, and varices presenting F2 or/and RC sign must be prophylactically treated according to the provider's standard of care. If the patient has undergone EGD within 180 days prior to enrollment and the presence of varices has been ruled out, a repeat procedure is not required.) 2.Thrombosis/embolism within 180 days prior to enrollment. 3.Has undergone major surgical procedures (open thoracotomy, open abdominal surgery, thoracoscopic surgery, laparoscopic surgery, etc.) within 28 days prior to enrollment. Has undergone an open wound biopsy or suture procedure for major trauma, or is scheduled to undergo major surgical procedures (open chest or abdominal surgery) during the study period. 4.Receiving systemic administration of immunostimulants (interferon, interleukin 2 [IL-2], etc.) within 180 days prior to registration. 5.Received systemic administration of immunosuppressive agents (e.g., corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, tumor necrosis factor [TNF]-a inhibitors) within 14 days prior to enrollment, or anticipated the need for systemic immunosuppressive agents during the study period, except if the subject has received mineralocorticoids (e.g., fludrocortisone) or corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma. 6.Active or prior of autoimmune disease or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn s disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Grave s disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). 7.History of another primary malignancy* (concurrent overlapping cancer and iatrogenic overlapping cancer with a disease-free interval of 5 years or less). * Epithelial cervical cancer, basal cell carcinoma, superficial bladder tumors, early stomach cancer, and early colorectal cancer that have been appropriately curatively treated are excluded. 8.Participating in another clinical study with an investigational product during the last 180 days 9.Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. 10.Any unresolved toxicity NCI CTCAE Grade >-2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with Grade >-2 neuropathy will be evaluated on a case-by-case basis after consultation with the Supervisor, principal investigator . Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Supervisor, principal investigator. 11.Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 12.History of allogenic organ transplantation. 13.History of leptomeningeal carcinomatosis 14.History of active primary immunodeficiency 15.Significant cardiovascular disease (New York Heart Association [NYHA] Class II or higher heart disease, myocardial infarction), unstable arrhythmia or unstable angina within 90 days prior to enrollment. 16.Pregnant, lactating, having a positive pregnancy test (pregnancy tests were performed on women who have menstruated within the past year) or not willing to use contraception during the study period. 17.Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 18.Clinically uncontrolled pleural or pericardial effusion or ascites 19.Complications of hepatic encephalopathy. 20.Serious complications as follows: Uncontrolled hypertension with or without antihypertensive use Severe infectious diseases (e.g., hospitalization due to complications of infection, bacteremia, severe pneumonia) within 28 days prior to enrollment. However, hepatitis B virus (HBV) and hepatitis C virus (HCV) are excluded. Undergoing hemodialysis due to renal failure, severe psychiatric disorders, allergic reaction to contrast media that interfere with angiography*. *Unable to receive both contrast CT and contrast MRI(registration is acceptable if either CT or MRI can be performed). 21.History of severe allergic or anaphylactic reactions to chimeric antibodies, humanized antibodies, or fusion proteins. 22.Hypersensitivity to components of Chinese hamster ovary cell-derived, tremelimumab or durvalumab products. 23.Bleeding disorder or history of gastrointestinal bleeding or active hemoptysis 24.Difficulty in oral intake 25.HIV-positive or active tuberculosis infection (clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). 26.Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of anti-HBc and absence of HBsAg) are eligible. Participants positive for HBsAg are eligible if polymerase chain reaction is negative for HBV DNA. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 27.Active pulmonary fibrosis or interstitial pneumonia 28.Blood transfusion was performed or G-CSF or other blood products were administered within 14 days prior to enrollment 29.Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. 30.Poor general condition and determined not suitable to participate in the study by an attending physician.