Durvalumab and Tremelimumab as First Line Treatment in Participants with Advanced Hepatocellular Carcinoma(HCC)
- Conditions
- Advanced unresectable hepatocellular carcinoma (HCC)
- Registration Number
- JPRN-jRCT2051230057
- Lead Sponsor
- Kim Young Hak
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 25
Confirmed HCC based on histopathological findings from tumour tissue
-Must not have received prior systemic therapy for HCC
-Minimum life expectancy of 12 weeks
-At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as >= 10 mm in the longest diameter with CT or MRI, and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines
-Must not be eligible for LRT for unresectable HCC.
-Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy LRT) or stage C
-Child-Pugh Score classification on liver disease and WHO/ECOG PS at enrolment complying one of the following:
(a)Child-Pugh score B7 or B8 with a WHO/ECOG PS of 0-1 at enrolment, without main trunk portal vein thrombosis.
(b)Child-Pugh class A with a WHO/ECOG PS of 2 at enrolment, without main trunk portal vein thrombosis (ie, ECOG PS 2 participants with main portal vein tumour thrombosis are excluded from this study).
(c)Child-Pugh class A with WHO/ECOG PS of 0-1 at enrolment and evidence of chronic main trunk portal vein thrombosis
-Participants with hepatitis B virus (HBV) infection must be treated with antiviral therapy prior to enrolment.
-Participants with hepatitis C virus (HCV) infection must have confirmed diagnosis of HCV characterized by the presence of detectable HCV RNA or anti-HCV upon enrolment
-Adequate organ and bone marrow function
-Negative pregnancy test (serum) for women of childbearing potential.
- Female participants must be 1 year post-menopausal, surgically sterile, or using one highly effective form of birth control
-Male and Female participants and their partners must use an acceptable method of contraception.
-Body weight >30 kg
-Any evidence of acute or uncontrolled diseases or history of allogeneic organ transplant
-Refractory nausea and vomiting, chronic gastrointestinal (GI) disease, inability to swallow a formulated product, or previous significant bowel resection
-History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia
-History of another primary malignancy except for:
a) Malignancy treated with curative intent with no known active disease >= 5 years before the first dose of study intervention and of low potential risk for recurrence, or
b) Basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or lentigo maligna that has undergone potentially curative therapy, or
c) Adequately treated carcinoma in situ without evidence of disease
-Persistent toxicities (Common Terminology Criteria for Adverse
Events [CTCAE] Grade > 2) caused by previous anticancer therapy
-Active or prior documented autoimmune or inflammatory disorders
-History of active primary immunodeficiency
-History of leptomeningeal carcinomatosis
-History of hepatic encephalopathy within the past 12 months or requirement for medications to prevent or control encephalopathy
-Active or prior documented GI bleeding (eg, esophageal varices or ulcer bleeding) within the past 6 months.
-Evidence of acute main trunk portal vein thrombosis
-History of previous, or current, brain metastases or spinal cord compression
-Known fibrolamellar hepatocellular carcinoma (HCC), sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Clinically meaningful ascites
- Participants co-infected with HBV and HCV or co-infected with HBV and hepatitis D virus (HDV)
-Known to have tested positive for human immunodeficiency virus (HIV) or active tuberculosis infection
-Prior exposure to immune-mediated therapy excluding therapeutic anticancer vaccines
-Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method - Incidence of grade 3 or 4 possibly related to treatment adverse events (PRAEs)<br>- Objective response rate (ORR)
- Secondary Outcome Measures
Name Time Method - Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse event of special interest (AESIs), immune-mediated AEs (imAEs)<br>- Overall Survival (OS)<br>- Progression-Free Survival (PFS)<br> Disease Control Rate at Week 16 (DCR-16w)<br>- Disease Control Rate at Week 24 (DCR-24w)<br>- Duration of Response (DOR)<br>- Duration of Treatment (DOT)<br>- Time to deterioration in Health-Related Quality of Life (HRQoL)<br>- Clinically meaningful change from baseline in HRQoL<br>- Best overall response for HRQoL<br>- Change from baseline in HRQo