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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03638141
Recruitment Status : Recruiting
First Posted : August 20, 2018
Last Update Posted : August 2, 2019
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Intermediate Stage of Hepatocellular Carcinoma Hepatocellular Carcinoma Drug: Durvalumab Drug: Tremelimumab (Cohort A dose) Drug: Tremelimumab (Cohort B dose) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 12, 2019
Estimated Primary Completion Date : November 2020
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Durvalumab

Arm Intervention/treatment
Experimental: Durvalumab in combination with 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.

Drug: Durvalumab
Durvalumab IV
Other Name: MEDI4736

Drug: Tremelimumab (Cohort A dose)
Tremelimumab IV
Other Name: CP-675,206

Experimental: Durvalumab in combination with 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.
Drug: Durvalumab
Durvalumab IV
Other Name: MEDI4736

Drug: Tremelimumab (Cohort B dose)
Tremelimumab IV
Other Name: CP-675,206




Primary Outcome Measures :
  1. Objective response rate (ORR) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. [ Time Frame: 2 years ]
    Proportion of participants with reduction in tumor burden as defined by mRECIST criteria.


Secondary Outcome Measures :
  1. Progression free survival (PFS) [ Time Frame: 2 years ]
    Number of months until disease progression or death

  2. Tumor response as determined by number of participants with partial (PR) or complete response (CR) as defined by mRECIST criteria [ Time Frame: 2 years ]
    PR is defined as >=30% reduction in size of target lesions, whereas CR is defined as disappearance of all target lesions

  3. Overall Survival (OS) [ Time Frame: 2 years ]
    Number of months until death from any-cause

  4. Number of participants experiencing study drug-related toxicities [ Time Frame: 2 years ]
    Number of participants experiencing drug-related adverse events >= Grade 3 or higher as defined by CTCAE v5.0



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03638141


Contacts
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Contact: Susan Sartorius-Mergenthaler, RN 410-614-3644 Sartosu@jhmi.edu
Contact: Richard Zak, RN 410-614-4208 rzak5@jhmi.edu

Locations
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United States, Maryland
Sidney Kimmel Comprehensive Cancer Center Recruiting
Baltimore, Maryland, United States, 21231
Contact: Susan Sartorius-Mergenthaler, RN    410-614-3644    Sartosu@jhmi.edu   
Contact: Richard Zak, RN    410-614-4208    rzak5@jhmi.edu   
Principal Investigator: Ana DeJesus, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
AstraZeneca
Investigators
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Principal Investigator: Ana De Jesus-Acosta, MD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03638141    
Other Study ID Numbers: J18118
IRB00179347 ( Other Identifier: JHM IRB )
First Posted: August 20, 2018    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
HCC
Durvalumab
Tremelimumab
Immunotherapy
PD-L1
Antibodies
Hepatocellular Carcinoma
CTLA-4
DEB-TACE
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Durvalumab
Ipilimumab
Tremelimumab
Antibodies, Monoclonal
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs