CTLA-4 /PD-L1 Blockade Following Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC (Hepatocellular Carcinoma) Using Durvalumab and Tremelimumab

Phase 2

Completed

Conditions: Intermediate Stage of Hepatocellular Carcinoma
Hepatocellular Carcinoma

Interventions: Drug: Durvalumab
Drug: Tremelimumab

Registration Number: NCT03638141

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary: The purpose of this study is to determine the safety and efficacy of immunotherapy durvalumab and tremelimumab combined with DEB-TACE in patients with Hepatocellular Carcinoma.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

Inclusion Criteria

Signed informed consent form
Age ≥18 years.
Patients with diagnosis of HCC either by high-resolution imaging (triple-phase CT or MRI) and/or by tumor biopsy.
Patient is not on systemic treatment for diagnosis of HCC
HCC meeting Barcelona Clinic Liver Cancer (BCLC) stage B (intermediate stage), with measurable lesions on CT or MRI and without extrahepatic spread
Have measurable disease
Have disease that responds to DEB-TACE
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Child-Pugh Score of A or early B (score ≤8) without clinically significant ascites
Body weight >30 kg
Patients must have adequate organ function defined by study-specified laboratory tests.
Evidence of post-menopausal status or negative pregnancy test
Willing and able to comply with study procedures
Willing to undergo a liver biopsy

Exclusion Criteria

Anyone involved with the planning and/or conduct of the study.
Has participated in another investigational study during the last 6 months.
Any concurrent anticancer therapy or received therapy ≤30 days prior to study.
Major surgical procedure at the time of study enrollment or within 28 days prior to the first dose of study drug.
Have a vascular invasion or extrahepatic tumor.
Main portal vein thrombosis present on imaging.
Uncontrolled hepatic encephalopathy at time of enrollment. - Ascites within 6 weeks prior to study treatment.
Any contraindications for embolization.
Has an active infection such as Tuberculosis, HIV, hepatitis B or C.
History of another primary malignancy or myeloproliferative disorder.
History of leptomeningeal carcinomatosis.
History of active primary immunodeficiency.
Any unresolved toxicities from previous anticancer therapy.
Active or prior documented GI bleeding due to ulcer or esophageal varices bleeding within 6 months.
History or current use of immunosuppressive medications within 14 days prior to study medications.
Major surgical procedure within 28 days prior to the first dose of IP.
Has an active known or suspected autoimmune disease.
Patients with hypothyroidism.
Any active skin conditions.
History of allogenic organ transplantation.
Significant heart disease.
Patients weighing < 30 kg.
Patients with celiac disease not controlled by diet alone.
Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Have received a live vaccine within 30 days prior to study drug.
Woman who are pregnant or breastfeeding.
Known allergy or hypersensitivity to the study drug.
Have received durvalumab, tremelimumab, anti-PD-1, anti-PD-L1 or anti-CTLA-4 in a prior study.
Unwilling or unable to follow the study schedule for any reason.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Durvalumab in combination with Tremelimumab	Durvalumab	Drug: Durvalumab 1500mg IV + Tremelimumab 300 mg IV , single infusion about 2 weeks after first DEB-TACE procedure. Drug: Durvalumab (monotherapy) 1500 mg IV infusion every 4 weeks, for maximum 13 doses/cycles.
Durvalumab in combination with Tremelimumab	Tremelimumab	Drug: Durvalumab 1500mg IV + Tremelimumab 300 mg IV , single infusion about 2 weeks after first DEB-TACE procedure. Drug: Durvalumab (monotherapy) 1500 mg IV infusion every 4 weeks, for maximum 13 doses/cycles.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	up to 26 months	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on mRECIST criteria. CR = Disappearance of any intratumoral arterial enhancement in all target lesions, PR = At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions.

Secondary Outcome Measures

Name	Time	Method
Drug-related Toxicity	up to 16 months	Number of participants experiencing drug-related adverse events (AE) Grade 3 or higher as defined by CTCAE v5.0
Progression Free Survival (PFS)	up to 58 months	Progression free survival is defined as the time from start of the treatment until the documentation of disease progression according to mRECIST or death due to any cause, whichever occurs first. Estimation based on the Kaplan-Meier curve.
Overall Survival (OS)	up to 58 months	Overall survival is the time from the start of first dose of study drug to death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

Trial Locations

Locations (1): Sidney Kimmel Comprehensive Cancer Center
🇺🇸
Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States