Actively Recruiting
Durvalumab and Tremelimumab in Resectable HCC
Led by University Health Network, Toronto · Updated on 2024-10-10
28
Participants Needed
3
Research Sites
157 weeks
Total Duration
On this page
Sponsors
U
University Health Network, Toronto
Lead Sponsor
C
Clinica Universidad de Navarra, Universidad de Navarra
Collaborating Sponsor
AI-Summary
What this Trial Is About
Hepatocellular Carcinoma (HCC) is the third most common cause of death from cancer world wide and the incidence is rising globally. Despite surgical resection in appropriate patients, many patients recur. The results of the IMbrave150 study have established PD-L1 inhibition in combination with VEGF inhibition as a new standard of care highlighting the role of immune checkpoint inhibition in advanced HCC. In addition, the combination of Tremelimumab and Durvalumab has demonstrated efficacy in advanced HCC; the HIMALAYA trial has now completed accrual in treatment naïve patients with advanced HCC. Furthermore the earlier use of immune checkpoint inhibitors in this disease are being explored with adjuvant combination strategies, including the EMERALD-2 trial (NCT03847428). Neoadjuvant treatment in HCC allows for delivery of treatment pre surgery and may enhance pathological responses and improve outcomes. The delivery of combination CTLA-4 and PD-L1 inhibition has demonstrated efficacy in other tumour types in the neoadjuvant setting where the impact on the tumour microenvironment has also been evaluated. The safety and feasibility of Durvalumab and Tremelimumab in resectable HCC has yet to be established. Hypotheses Pre-operative (pre-op) Durvalumab and Tremelimumab treatment is safe and feasible in pre surgical setting for upfront resectable HCC The combination of Durvalumab and Tremelimumab pre-op will result in changes in immune and molecular characteristics within the tumour microenvironment. Overall Study Design This is a phase II, open-label multi-centre study to assess safety of Durvalumab and Tremelimumab treatment in pre-op setting for upfront resectable HCC, followed by adjuvant Durvalumab. 28 patients are expected to enrol at three sites. Patients will receive pre-op: 1 dose Tremelimumab (300mg) (T300) with Durvalumab (1500mg) at cycle 1 and 1 further cycle of Durvalumab (1500mg) only. Post-surgical resection, adjuvant therapy will consist of Durvalumab Q4W for up to a maximum of 12 months in total or 13 cycles of Durvalumab (11 cycles post op). All participants will be treated until progressive disease or unacceptable toxicity or withdrawal of consent or another discontinuation criterion is met. All participants will be followed for survival until the end of study. No dose reductions of Tremelimumab and Durvalumab will be allowed. Statistics The primary objective of this study is to assess safety of pre-op treatment with Durvalumab and Tremelimumab. For safety, with the null proportion of patients who discontinue treatment due to AEs, imAEs or SAE is 30% versus the alternative proportion is 10% or less than 10%, a sample size of 28 provides 80% power to detect the proportion difference with a two-sided alpha level of 0.1. The sample size estimate is based on the two-sided exact test for binomial proportion considering Binomial Enumeration method.
CONDITIONS
Official Title
Durvalumab and Tremelimumab in Resectable HCC
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Able to provide written informed consent
- Age over 18 years at time of study entry
- Histologically confirmed resectable hepatocellular carcinoma (early and intermediate stage)
- Willing to provide a biopsy sample before treatment
- ECOG performance status of 0 or 1
- Child-Pugh liver function score of 5 or 6
- ALBI grade 1
- If infected with hepatitis B virus (HBV), must be on antiviral therapy with viral suppression before study entry and continue therapy during study and 6 months after last dose
- If infected with hepatitis C virus (HCV), must have disease managed according to local practice
- Female participants must be post-menopausal or have a negative pregnancy test if pre-menopausal
- Female participants of childbearing potential and male partners agree to use effective contraception during treatment and for 6 months after last dose
- Adequate blood and organ function as defined by specific laboratory values within screening period
- Willing and able to comply with study protocol and visits
- Body weight greater than 30 kg
You will not qualify if you...
- Fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
- Any prior therapy for HCC except one curative surgery or ablation done at least 2 years before enrollment
- Evidence of distant metastasis, co-existing cancer, or macrovascular invasion on baseline imaging
- History of hepatic encephalopathy in past 12 months or requiring medications for encephalopathy
- Portal vein thrombosis (Vp1, Vp2, Vp3, or Vp4) on baseline imaging
- Clinically significant ascites requiring intervention within 6 months prior to treatment
- History of nephrotic or nephritic syndrome
- Symptomatic congestive heart failure (NYHA II-IV) or uncontrolled cardiac arrhythmia
- Active or prior autoimmune or inflammatory disorders except specified exceptions
- Uncontrolled intercurrent illness or conditions limiting compliance
- History of other primary malignancy except certain low-risk or treated cancers
- Concurrent chemotherapy, investigational product, biologic, or hormonal cancer therapy
- Active infections including tuberculosis or HIV
- Co-infection with HBV and HCV or HBV and hepatitis D
- Known allergy to study treatments or excipients
- Major surgery within 28 days or central venous access device placement within 7 days before enrollment
- QTcF interval ≥470 ms on ECG
- History of active primary immunodeficiency
- History of allogeneic organ transplantation or waiting list for liver transplantation
- Receipt of live vaccine within 30 days before first dose or planned during study
- Current or recent immunosuppressive medication use except specified exceptions
- Pregnant or breastfeeding women or those unwilling to use effective birth control during and after study treatment
AI-Screening
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Trial Site Locations
Total: 3 locations
1
University Health Network
Toronto, Ontario, Canada, M5G 2M9
Actively Recruiting
2
University of Milan
Milan, Italy, 20122
Not Yet Recruiting
3
Clinica Universidad De Navarra
Pamplona, Spain, 31008
Not Yet Recruiting
Research Team
C
Claudia Sweeney
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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