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

The Effect of CTLA-4/PD-L1 Blockade Following Drug-eluting Bead Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC Using Durvalumab (MEDI4736) and Tremelimumab

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma; Intermediate Stage of Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Durvalumab; Drug: Tremelimumab (Cohort A dose); Drug: Tremelimumab (Cohort B dose)

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joann Santmyer, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu
• Study Contact Backup: Name: Colleen Apostal, RN; Phone Number: 410-614-3644; Email: GIClinicalTrials@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent form
• Age ≥18 years.
• Newly diagnosed with hepatocellular carcinoma
• Have measurable disease
• Have disease that responds to DEB-TACE
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Body weight >30 kg
• Evidence of clinical or radiographic ascites with a score < 7
• 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 IP.
• Have a diffuse HCC (Hepatocellular Carcinoma), vascular invasion or extrahepatic tumor.
• Main portal vein thrombosis present on imaging.
• History of hepatic encephalopathy within past 12 months or require medications to prevent or control encephalopathy.
• Ascites within 6 weeks prior to study treatment.
• Any contraindications for embolization.
• Has an active infection such as TB, HIV, hepatitis B or C.
• History of another primary malignancy.
• History of leptomeningeal carcinomatosis.
• History of active primary immunodeficiency.
• Any unresolved toxicities from previous anticancer therapy.
• Grade ≥2 neuropathy.
• History of bleeding disorder.
• History or current use of immunosuppressive medications within 14 days prior to study medications.
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Durvalumab in combination with Tremelimumab (Cohort A dose); Starting at week 2, after initial DEB-TACE treatment, patients will receive Durvalumab in combination with tremelimumab, as specified per protocol (Cohort A dose). Treatment will continue for up to 12 months, while receiving DEB-TACE. Repeat DEB-TACE will be provided Q8W if there is residual tumor that can be targeted.	Drug: Durvalumab; Durvalumab IV; Other Names: MEDI4736; Drug: Tremelimumab (Cohort A dose); Tremelimumab IV; Other Names: CP-675,206
Experimental: Durvalumab in combination with Tremelimumab (Cohort B dose); Starting at week 2, after initial DEB-TACE treatment, patients will receive Durvalumab in combination with tremelimumab as specified per protocol (Cohort B dose). Treatment will continue for up to 12 months, while receiving DEB-TACE. Repeat DEB-TACE will be provided Q8W if there is residual tumor that can be targeted.	Drug: Durvalumab; Durvalumab IV; Other Names: MEDI4736; Drug: Tremelimumab (Cohort B dose); Tremelimumab IV; Other Names: CP-675,206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.	Proportion of participants with reduction in tumor burden as defined by mRECIST criteria.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS)	Number of months until disease progression or death	2 years
Tumor response as determined by number of participants with partial (PR) or complete response (CR) as defined by mRECIST criteria	PR is defined as >=30% reduction in size of target lesions, whereas CR is defined as disappearance of all target lesions	2 years
Overall Survival (OS)	Number of months until death from any-cause	2 years
Number of participants experiencing study drug-related toxicities	Number of participants experiencing drug-related adverse events >= Grade 3 or higher as defined by CTCAE v5.0	2 years

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Ana De Jesus-Acosta, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2019
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 15, 2018
• First Submitted That Met QC Criteria: August 16, 2018
• First Posted (Actual): August 20, 2018

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; HCC; Immunotherapy; PD-L1; Antibodies; Durvalumab; CTLA-4; Tremelimumab; DEB-TACE
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Durvalumab; Tremelimumab; Antibodies, Monoclonal; Ipilimumab
• Other Study ID Numbers: J18118; IRB00179347 (Other Identifier: JHM IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No