Durvalumab (MEDI4736) and Tremelimumab for Hepatocellular Carcinoma in Patients Listed for a Liver Transplant
Overview
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Davendra Sohal
- Enrollment
- 30
- Locations
- 3
- Primary Endpoint
- Cellular rejection rates
Overview
Brief Summary
Immunotherapy can safely downstage patients and achieve durable systemic disease control to improve clinical outcomes in HCC patients undergoing liver transplant.
Detailed Description
ESR-20-21010 is a single-arm, open-label, Phase II, multicenter clinical trial designed to evaluate the safety and efficacy of durvalumab and tremelimumab for the treatment of hepatocellular carcinoma (HCC) patients who have cirrhosis or portal hypertension and are evaluated by institutional Liver Transplant team and deemed eligible for transplant.
The key eligibility requirements include HCC, Child-Pugh score of up to 7, and ECOG PS of 0 or 1.
Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant.
The primary endpoint is proportion of patients experiencing post-transplant rejection (within 30 days of transplant). A total of 30 patients are to be enrolled, to allow at least 20 transplants for adequate primary endpoint analysis. An interim analysis after 10 patients will be performed to ensure safety. If there are untoward safety signals, study modification/discontinuation will be discussed.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Hepatocellular carcinoma, diagnosed either by biopsy or by combination of cirrhosis and imaging criteria (contrast-enhanced CT or MRI).
- •Tumor confined to liver with no vascular invasion and no evidence of extrahepatic disease.
- •Patient evaluated by institutional Liver Transplant team and listed for transplant.
- •At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion (TL) at baseline. Tumor assessment by computed tomography (CT) scan or magnetic resonance imaging (MRI) must be performed within 28 days prior to randomization.
- •No prior therapy for HCC at any time.
- •Age ≥18 years at the time of study entry.
- •ECOG score of 0 or 1
- •Child-Pugh Score of 5, 6, or 7
- •Body weight \>30 kg
- •Patients must have adequate organ and marrow function as defined in protocol
Exclusion Criteria
- •Extrahepatic disease.
- •Variceal bleeding during 3 months prior to registration.
- •Any autoimmune disease deemed a risk in the setting of immunotherapy per treating physician's judgment.
- •Any other illness or patient condition deemed a medical or logistical barrier for protocol therapy per treating physician's judgment.
- •Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study
- •Participation in another clinical study with an investigational product during the last 12 months Patients who have received other investigational agents previously who are no longer receiving these investigational agents may be eligible at the discretion of the PI.
- •Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
- •History of allogenic organ transplantation.
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence
Arms & Interventions
Durvalumab + Tremelimumab + Liver Transplant
Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant.
Intervention: Durvalumab (Drug)
Durvalumab + Tremelimumab + Liver Transplant
Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant.
Intervention: Tremelimumab (Drug)
Durvalumab + Tremelimumab + Liver Transplant
Patients will be treated with the immunotherapy combination for up to 4 months. After a minimum 28 day washout, they will undergo locoregional therapy per institutional standards. Eventually, after a minimum 72-day washout from the end of immunotherapy, they will undergo liver transplant.
Intervention: Liver Transplant (Procedure)
Outcomes
Primary Outcomes
Cellular rejection rates
Time Frame: Up to 30 days post transplant
To assess the safety of immunotherapy for treatment of HCC in patients listed for a liver transplant, with respect to cellular rejection rates
Secondary Outcomes
- Adverse events during treatment, and graft loss and mortality rates(Treatment, and up to 30 days post transplant)
- Radiologic responses via RECIST 1.1 and/or mRECIST(Survival follow up will continue for 5 years after end of Treatment)
- Pathologic responses via explanted liver assessment(Survival follow up will continue for 5 years after end of Treatment)
- Recurrence-free survival and overall survival outcomes based on survival follow up reporting(Survival follow up will continue for 5 years after end of Treatment)
Investigators
Davendra Sohal
Principal Investigator
University of Cincinnati