Hepatocellular Carcinoma Hepatocellular Carcinoma
Conditions
Interventions
To assess the safety of multimodal treatment of unresectable hepatocellular carcinoma with durvalumab plus tremelimumab and surgical resection.
Sponsors
Eguchi Susumu
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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)>>-9.0 g/dL Absolute neutrophil count (ANC >-1000/uL) Platelet count >-75000 /uL Serum bilirubin > AST (SGOT)/ALT (SGPT) -2.8g/dL International normalized ratio (INR) 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 di
Exclusion criteria
Exclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of postoperative complications of the Clavien-Dindo grade 3 or higher in patients receiving hepatectomy | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Contacts
Public ContactHajime Matsushima
Nagasaki University Hospital
Outcome results
None listed