Description:
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.
Title
- Brief Title: 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
Clinical Trial IDs
- ORG STUDY ID:
J18118
- SECONDARY ID:
IRB00179347
- NCT ID:
NCT03638141
Conditions
- Intermediate Stage of Hepatocellular Carcinoma
- Hepatocellular Carcinoma
Interventions
Drug | Synonyms | Arms |
---|
Durvalumab | MEDI4736 | Durvalumab in combination with Tremelimumab (Cohort A dose) |
Tremelimumab (Cohort A dose) | CP-675,206 | Durvalumab in combination with Tremelimumab (Cohort A dose) |
Tremelimumab (Cohort B dose) | CP-675,206 | Durvalumab in combination with Tremelimumab (Cohort B dose) |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Durvalumab in combination with Tremelimumab (Cohort A dose) | Experimental | 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
- Tremelimumab (Cohort A dose)
|
Durvalumab in combination with Tremelimumab (Cohort B dose) | Experimental | 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
- Tremelimumab (Cohort B dose)
|
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent form
- Age 18-75 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.
Maximum Eligible Age: | 75 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Proportion of participants with reduction in tumor burden as defined by mRECIST criteria. |
Secondary Outcome Measures
Measure: | Progression free survival (PFS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Number of months until disease progression or death |
Measure: | Tumor response as determined by number of participants with partial (PR) or complete response (CR) as defined by mRECIST criteria |
Time Frame: | 2 years |
Safety Issue: | |
Description: | PR is defined as >=30% reduction in size of target lesions, whereas CR is defined as disappearance of all target lesions |
Measure: | Overall Survival (OS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Number of months until death from any-cause |
Measure: | Number of participants experiencing study drug-related toxicities |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Number of participants experiencing drug-related adverse events >= Grade 3 or higher as defined by CTCAE v5.0 |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- HCC
- Durvalumab
- Tremelimumab
- Immunotherapy
- PD-L1
- Antibodies
- Hepatocellular Carcinoma
- CTLA-4
- DEB-TACE
Last Updated
August 20, 2021