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
Active, not recruiting
- Conditions
- Intermediate Stage of Hepatocellular CarcinomaHepatocellular Carcinoma
- Interventions
- Registration Number
- NCT03638141
- 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
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 30
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Durvalumab in combination with Tremelimumab (Cohort B dose) 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. Durvalumab in combination with Tremelimumab (Cohort A dose) 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. Durvalumab in combination with Tremelimumab (Cohort A dose) Durvalumab 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. Durvalumab in combination with Tremelimumab (Cohort B dose) Durvalumab 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.
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. 2 years Proportion of participants with reduction in tumor burden as defined by mRECIST criteria.
- Secondary Outcome Measures
Name Time Method Progression free survival (PFS) 2 years Number of months until disease progression or death
Tumor response as determined by number of participants with partial (PR) or complete response (CR) as defined by mRECIST criteria 2 years PR is defined as \>=30% reduction in size of target lesions, whereas CR is defined as disappearance of all target lesions
Overall Survival (OS) 2 years Number of months until death from any-cause
Number of participants experiencing study drug-related toxicities 2 years Number of participants experiencing drug-related adverse events \>= Grade 3 or higher as defined by CTCAE v5.0
Trial Locations
- Locations (1)
Sidney Kimmel Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States