Clinical trial NCT03638141: CTLA-4 /PD-L1 Blockade Following Transarterial Chemoembolization (DEB-TACE) in Patients With Intermediate Stage of HCC (Hepatocellular Carcinoma) Using Durvalumab and Tremelimumab
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Intermediate Stage of Hepatocellular Carcinoma
Hepatocellular Carcinoma
Keywords: HCC
Durvalumab
Tremelimumab
Immunotherapy
PD-L1
Antibodies
Hepatocellular Carcinoma
CTLA-4
DEB-TACE
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2018-08-20
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.
timeFrame: 2 years
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 2 years
measure: Tumor response as determined by number of participants with partial (PR) or complete response (CR) as defined by mRECIST criteria
timeFrame: 2 years
measure: Overall Survival (OS)
timeFrame: 2 years
measure: Number of participants experiencing study drug-related toxicities
timeFrame: 2 years
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Ana De Jesus-Acosta, MD
role: PRINCIPAL_INVESTIGATOR
References: