Durvalumab for Advanced Hepatocellular Carcinoma in Patients With Active Chronic Hepatitis B Virus Infection
- Conditions
- Advanced Hepatocellular Carcinoma
- Registration Number
- NCT04294498
- Lead Sponsor
- National Taiwan University Hospital
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 30
Inclusion criteria<br><br> - Capable of giving signed informed consent which includes compliance with the<br> requirements and restrictions listed in the informed consent form (ICF) and in this<br> protocol. Written informed consent and any locally required authorization obtained<br> from the patient/legal representative prior to performing any protocol-related<br> procedures, including screening evaluations.<br><br> - Histologically or clinically (typical HCC imaging findings by multi-phase CT or MRI)<br> diagnosed HCC.<br><br> - Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not<br> amenable to locoregional therapy.<br><br> - HBeAg (-) active chronic HBV infection, defined by positive serum HBsAg AND serum<br> HBV DNA = 2,000 IU/mL.<br><br> - No previous immune checkpoint inhibitor treatment<br><br> - The patient refuses, has disease progression on, or does not tolerate treatment<br> kinase inhibitors such as sorafenib or lenvatinib<br><br> - Age > 20 years at time of study entry.<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1<br><br> - Child-Pugh class A<br><br> - =1 measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1<br><br> - Body weight >30 kg<br><br> - Adequate normal organ and marrow function as defined below:<br><br> 1. Haemoglobin =9.0 g/dL<br><br> 2. Absolute neutrophil count (ANC) =1.0 x 109/L (> 1,000 per mm3)<br><br> 3. Platelet count =75 x 109/L (>75,000 per mm3)<br><br> 4. Serum bilirubin =2 x institutional upper limit of normal (ULN).<br><br> 5. AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless active<br> liver malignancies are present, in which case it must be =5x ULN<br><br> 6. Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40<br> mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour<br> urine collection for determination of creatinine clearance<br><br> - Evidence of post-menopausal status or negative urinary or serum pregnancy test for<br> female pre-menopausal patients. Women will be considered post-menopausal if they<br> have been amenorrheic for 12 months without an alternative medical cause.<br><br> - Patient is willing and able to comply with the protocol for the duration of the<br> study including undergoing treatment and scheduled visits and examinations including<br> follow up.<br><br> - Must have a life expectancy of at least 12 weeks<br><br>Exclusion criteria<br><br> - Serum HBeAg (+)<br><br> - Fibrolamellar carcinoma or mixed hepatocellular cholangiocarcinoma<br><br> - Active or prior documented GI variceal bleed or history of upper GI bleeding,<br> ulcers, or esophageal varices with bleeding within 12 months; adequate endoscopic<br> therapy according to institutional standards is required for patients with history<br> of esophageal variceal bleeding or assessed as high risk for esophageal variceal by<br> the treating investigator.<br><br> - Previous organ transplants<br><br> - Participation in another clinical study with an investigational product during the<br> last 2 weeks<br><br> - Concurrent enrollment in another clinical study, unless it is an observational<br> (non-interventional) clinical study or during the follow-up period of an<br> interventional study<br><br> - Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy,<br> endocrine therapy, targeted therapy, biologic therapy, tumor embolization,<br> monoclonal antibodies) =14 days prior to the first dose of study drug. If sufficient<br> wash-out time has not occurred due to the schedule or PK properties of an agent, a<br> longer wash-out period will be required, as agreed by the principal investigator<br><br> - Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the<br> exception of alopecia, vitiligo, and the laboratory values defined in the inclusion<br> criteria<br><br> - Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.<br> Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone<br> replacement therapy) is acceptable.<br><br> - Major surgical procedure (as defined by the Investigator) within 28 days prior to<br> the first dose of study treatment.<br><br> - Active or prior documented autoimmune or inflammatory disorders (including<br> inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with<br> the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis<br> syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease,<br> rheumatoid arthritis, hypophysitis, uveitis, etc]).<br><br> - Uncontrolled intercurrent illness, including but not limited to, ongoing or active<br> infection (except HBV infection), symptomatic congestive heart failure, uncontrolled<br> hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung<br> disease, serious chronic gastrointestinal conditions associated with diarrhea, or<br> psychiatric illness/social situations that would limit compliance with study<br> requirement, substantially increase risk of incurring AEs or compromise the ability<br> of the patient to give written informed consent<br><br> - History of another primary malignancy except for<br><br> 1. Malignancy treated with curative intent and with no known active disease =5<br> years before the first dose of IP and of low potential risk for recurrence<br><br> 2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence<br> of disease<br><br> 3. Adequately treated carcinoma in situ without evidence of disease<br><br> - History of leptomeningeal carcinomatosis<br><br> - Brain metastases or spinal cord compression. Patients with suspected brain<br> metastases at screening should have an MRI (preferred) or CT each preferably with IV<br> contrast of the brain prior to study entry<br><br> - History of active primary immunodeficiency or HIV infection<br><br> - Active infection including tuberculosis (clinical evaluation that includes clinical<br> history, physical examination and radiographic findings, and TB testing in line with<br> local practice), and hepatitis C<br><br> - Current or prior use of immunosuppressive medication within 14 days before the first<br> dose of durvalumab.<br><br> - Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.<br> Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and<br> up to 30 days after the last dose of IP.<br><br> - Female patients who are pregnant or breastfeeding or male or female patients of<br> reproductive potential who are not willing to employ effective birth control from<br> screening to 90 days after the last dose of durvalumab monotherapy.<br><br> - Known allergy or hypersensitivity to any of the study drugs or any of the study drug<br> excipients.<br><br> - Prior randomisation or treatment in a previous durvalumab clinical study regardless<br> of treatment arm assignment.
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The rate of HBV reactivation during durvalumab treatment
- Secondary Outcome Measures
Name Time Method The rate of hepatitis flare during durvalumab treatment;To assess the rate of HBV-associated hepatitis during durvalumab treatment.;To assess the efficacy of durvalumab treatment;To assess the efficacy of durvalumab treatment;To assess the efficacy of durvalumab treatment;To assess the efficacy of durvalumab treatment;To assess the adverse events during durvalumab treatment.