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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03638141
• Other study ID #: J18118
• Secondary ID: IRB00179347
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 2, 2019
• Est. completion date: December 2024

Study information

• Verified date: December 2023
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Intermediate Stage of Hepatocellular Carcinoma

Intervention

Drug:
• Durvalumab
Durvalumab IV
• Tremelimumab (Cohort A dose)
Tremelimumab IV
• Tremelimumab (Cohort B dose)
Tremelimumab IV

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	AstraZeneca

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression free survival (PFS)	Number of months until disease progression or death	2 years
Secondary	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
Secondary	Overall Survival (OS)	Number of months until death from any-cause	2 years
Secondary	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