Clinical Trials /

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

NCT03638141

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.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

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

DrugSynonymsArms
DurvalumabMEDI4736Durvalumab in combination with Tremelimumab (Cohort A dose)
Tremelimumab (Cohort A dose)CP-675,206Durvalumab in combination with Tremelimumab (Cohort A dose)
Tremelimumab (Cohort B dose)CP-675,206Durvalumab 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

NameTypeDescriptionInterventions
Durvalumab in combination with Tremelimumab (Cohort A dose)ExperimentalStarting 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)ExperimentalStarting 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

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