Durvalumab and Tremelimumab as First Line Treatment in Participants with Advanced Hepatocellular Carcinoma(HCC)

JRCT ID: jRCT2051230057

Registered date:25/06/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Advanced unresectable hepatocellular carcinoma (HCC)
• Date of first enrollment: 26/07/2023
• Target sample size: 20
• Countries of recruitment: France,Japan,Italy,Japan,Germany,Japan,Spain,Japan,Hong Kong,Japan,South Korea,Japan,Singapore,Japan,Vietnam,Japan,USA,Japan
• Study type: Interventional

Intervention(s)

- Durvalumab: Participants will receive 1500 mg at Day 1 and later receive as monotherapy starting at Week 4 for every 4 weeks through IV infusion
- Tremelimumab: Participants will receive single dose of 300 mg through IV infusion at Day 1

Outcome(s)

Primary Outcome

- Incidence of grade 3 or 4 possibly related to treatment adverse events (PRAEs)
- Objective response rate (ORR)

Secondary Outcome

- Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse event of special interest (AESIs), immune-mediated AEs (imAEs)
- Overall Survival (OS)
- Progression-Free Survival (PFS)
- Disease Control Rate at Week 16 (DCR-16w)
- Disease Control Rate at Week 24 (DCR-24w)
- Duration of Response (DOR)
- Duration of Treatment (DOT)
- Time to deterioration in Health-Related Quality of Life (HRQoL), assessed using the EORTC QLQ C-30
- Clinically meaningful change from baseline in HRQoL as assessed by EORTC QLQ C-30
- Best overall response for HRQoL as assessed by EORTC QLQ C-30
- Change from baseline in HRQoL as assessed by EORTC QLQ C-30
- Time to deterioration in HRQoL as assessed by EORTC QLQ-HCC18
- Clinically meaningful change from baseline in HRQoL as assessed by EORTC QLQ-HCC18
- Best overall response for HRQoL as assessed by EORTC QLQ-HCC18
- Change from baseline in HRQoL as assessed by EORTC QLQ-HCC18

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

-Confirmed unresectable HCC based on histopathological findings from tumour tissue, or radiological findings in participants where histopathological confirmation is not clinically feasible
-Must not have received prior systemic therapy for HCC
-Participants expected to live 12 weeks or more
-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

Exclude criteria

-Any evidence of acute or uncontrolled diseases, chronic diverticulitis or previous complicated diverticulitis, or history of allogeneic organ transplant, which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol
-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 >= 2 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 > 1) caused by previous anticancer therapy
-Active or prior documented autoimmune or inflammatory disorders, autoimmune pneumonitis, and autoimmune myocarditis
-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
-Any concomitant medication known to be associated with Torsades de Pointes
-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
-Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention and Major surgical procedure (as defined by the investigator) or significant traumatic injury within 4 weeks of the first dose of study intervention

Related Information

• Primary Sponsor: Sasaki Hidefumi
• Secondary ID(s): 2022-502012-37-00,05883644