None listed
Conditions
Interventions
Drug, Radiation : Transarterial radioembolization (TARE) with yttrium-90 microspheres will be employed in combination with an intravenous (IV) dose of 1500 mg durvalumab every 4 weeks (Q4W) until PD.
Sponsors
Seoul National University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 2. Male or female, aged >19 years at time of study entry. 3. Diagnosed with unequivocal HCC confirmed histologically or diagnosed radiologically according to American Association for the Study of Liver Diseases practice guideline 4. Locally advanced HCC, defined as Barcelona clinic liver cancer (BCLC) staging intermediate (B) stage or BCLC advanced stage (C) without extrahepatic metastasis 5. Must have at least 1 untreated measurable disease (untreated target lesion i.e. a viable lesion that has never been treated with locoregional treatment [transarterial chemoembolization {TACE}, TARE, percutaneous ethanol injection therapy, or radiofrequency ablation]) 6. Child-Pugh score =7 points 7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 8. Life expectancy of >12 weeks 9. Body weight >30 kg 10. Adequate normal organ and marrow function as defined below: - Hemoglobin =9.0 g/dL - Absolute neutrophil count (ANC) >1500 per mm3 - Platelet count >75,000 per mm3 - Serum bilirubin =1.5 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 the Investigator). - Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =5 x institutional upper limit of normal - Measured creatinine clearance >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine CL: 11. Female patients must be either postmenopausal or, if premenopausal, must have a negative pregnancy test and agree to use 2 forms of contraception, if sexually active during their study participation. Male patients must be surgically sterile or, if sexually active and having a pre-menopausal female partner then, must be using an acceptable form of contraception. Adequate contraception allowed in this trial is as follows: • Hormonal contraceptives such as combined oral contraceptive pill • Intrauterine devices or the implantation of intrauterine system (IUS) • Blockage methods (spermicides and condoms/spermicides and vaginal diaphragm for contraception, vaginal sponges or cervical cap) • Sterilization surgery such as tubal ligation in females and vasectomy in males 12. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply: - Women <50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent
Exclusion criteria
Exclusion criteria: 1. Eligible for potentially curative treatment (surgical resection, radio-frequency ablation or immediate liver transplantation) 2. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti- Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune pathways, including prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment 3. History of organ transplantation or hematopoietic stem cell transplantation 4. Any other concurrent malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, papillary thyroid cancer, early gastric cancer, or other cancer for which the patient has been disease-free for at least five years. 5. Evidence of extrahepatic metastasi(e)s, except for regional lymph node(s) involvement 6. A history of a severe contrast allergy (i.e. anaphylaxis) not controlled with premedication 7. Any condition that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of patient safety or study results 8. Participation in another clinical study with an investigational product during the last 8 weeks or 5 half-lives of the study drug, whichever is longer, prior to screening 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. Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) =1 cycle length or 14 days, whichever is longer, prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as determined by the Investigator. 11. 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 Study Physician. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included at the discretion of the Investigator. 12. 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. 13. Prior hepatic radiation therapy including Total Body Irradiation (TBI) for HCC or other malignancy. 14. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable. 15. Active or prior documented autoimmune 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, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (e.g., following Hashimoto synd
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| to evaluate time to progression (TTP) from enrolment using Modified Response Evaluation Criteria in Solid Tumors (mRECIST). | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) from first dose of study drug until the time of data cut-off, as determined by the Investigator.;Objective Response Rate (ORR) of Target Lesion(s) and Non-Target Lesion(s);The safety of durvalumab, regardless of causality. | — |
Countries
Korea, Republic of
Contacts
Public ContactYOONJUN KIM
Seoul National University Hospital
Outcome results
None listed