Phase II Study of Durvalumab and Tremelimumab with Personalized or Standard SIRT in Non-Resectable Hepatocellular Carcinoma

Trial ID: 2024-515127-11-00
Protocol: ESR-19-14451
Sponsor: Klinikum der Universitaet Muenchen AöR

Trial statistics

science

test molecules

location_city

research sites

public

countries

medical_information

disease

person_search

investigators

handshake

vendor

Diseases & Conditions

Hepatocellular carcinoma

Objectives

The primary objective of this study is to assess the **objective response rate** in patients with non-resectable hepatocellular carcinoma (HCC) using a treatment strategy that combines first-line systemic treatment with selective internal radiation therapy (SIRT), compared to standard SIRT as a historical control. This evaluation is clinically relevant as it aims to determine the efficacy of combining systemic immunotherapy with SIRT in improving tumor response in HCC, a condition with limited treatment options and poor prognosis.

Secondary objectives include:

Evaluating the safety and quality of life of treatment with durvalumab and tremelimumab in combination with SIRT.
Assessing overall survival, progression-free survival, time to progression, and disease control rate in patients treated with durvalumab and tremelimumab in combination with SIRT.

Participants

The clinical trial involves participants diagnosed with **hepatocellular carcinoma** (HCC), focusing on individuals with non-resectable disease. The study population includes both male and female subjects, with an age range corresponding to categories 3 and 4, which typically represent adults and older adults. Participants are required to have a histological diagnosis of HCC, a life expectancy of at least 12 weeks, and a disease not suitable for curative surgical or ablation treatment but eligible for transarterial chemoembolization (TACE) with a tumor burden of less than 50% of liver volume. The trial includes individuals with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, indicating fully active or restricted in physically strenuous activity but ambulatory. Participants must also have preserved liver function, as defined by a Child-Pugh score A and serum Bilirubin levels less than 1.5 times the institutional upper limit of normal. The trial population selection criteria ensure a focus on a vulnerable population, although the total number of participants is not provided by the sponsor.

Plans and Procedures

The clinical trial is designed as a **randomized**, open-label, phase II study to evaluate the efficacy of **durvalumab** and **tremelimumab** in combination with personalized selective internal radiation therapy (p-SIRT), standard-dose SIRT (sd-SIRT), or immunotherapy followed by on-demand loco-regional SIRT (od-SIRT) in patients with non-resectable **hepatocellular carcinoma** (HCC). The primary objective is to assess the objective response rate (ORR) in these patients, comparing the treatment strategy with historical controls of standard SIRT. Secondary endpoints include overall survival (OS), progression-free survival (PFS), complete response rate (CRR), disease control rate (DCR), and duration of response (DoR), among others. The trial is expected to commence recruitment on March 31, 2024, and conclude by December 31, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a histological diagnosis of HCC, a life expectancy of at least 12 weeks, and preserved liver function. The trial will involve multiple follow-up visits to monitor treatment response and safety, with the end-of-study visit marking the conclusion of participant involvement. The expected duration of participant involvement is up to 12 months, depending on the treatment arm. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent.

The investigational products, **durvalumab** and **tremelimumab**, are administered as solutions for infusion. **Durvalumab** has a maximum daily dose of 1500 mg, while **tremelimumab** is limited to 300 mg. The trial's methodology ensures rigorous assessment of the treatment's impact on non-resectable HCC, with a focus on both efficacy and safety outcomes. Participants will be closely monitored throughout the trial to ensure adherence to protocol and to address any potential complications promptly.

Treatment

The clinical trial involves the administration of **DURVALUMAB**, an experimental medication used in the treatment of non-resectable hepatocellular carcinoma (HCC). DURVALUMAB is provided as a **solution for infusion** and is administered intravenously. The maximum daily dose is 1500 mg, with a total treatment period extending up to 12 months. DURVALUMAB is a protein-based therapeutic agent, specifically classified under the category of "Protein - Other." The administration schedule and participant compliance are closely monitored to ensure adherence to the dosing regimen.

Another experimental medication used in this trial is **TREMELIMUMAB**, also formulated as a **solution for infusion**. TREMELIMUMAB is administered intravenously with a maximum daily dose of 300 mg. The treatment period for TREMELIMUMAB is limited to 1 month. Similar to DURVALUMAB, TREMELIMUMAB is a protein-based therapeutic agent, categorized under "Protein - Other." The administration of TREMELIMUMAB is conducted under strict compliance monitoring to ensure accurate dosing and participant adherence.

In addition to the experimental medications, the study incorporates personalized selective internal radiation therapy (p-SIRT), standard-dose SIRT (sd-SIRT), or immunotherapy followed by on-demand loco-regional SIRT (od-SIRT) as part of the treatment strategy. These non-experimental treatments serve as comparator therapies to evaluate the efficacy of the experimental medications in combination with SIRT in achieving an objective response rate in patients with non-resectable HCC. The trial design includes a randomized open-label phase II study to assess the treatment outcomes compared to historical controls.

Efficacy

The efficacy of the clinical trial will be assessed primarily through the **Objective Response Rate (ORR)**, comparing the treatment strategy involving first-line systemic treatment combined with Selective Internal Radiation Therapy (SIRT) to standard SIRT, using historical control data. Secondary endpoints include overall survival (OS), progression-free survival (PFS), complete response rate (CRR), disease control rate (DCR), and duration of response (DoR). Additionally, the trial will evaluate the time to deterioration of liver function, time to locally/locoregional untreatable progression (TTuP), and time to stage progression. Quality of life (QoL) will also be assessed using the EORTC QLQ-C30 and EORTC QLQ-HCC18 questionnaires.

Measurements and data collection will be conducted at specified intervals throughout the trial, with the primary endpoint being the ORR. The secondary endpoints will be measured and analyzed using validated scales and laboratory tests, ensuring the reliability and accuracy of the data. The trial is designed to provide comprehensive insights into the efficacy of the treatment strategy in patients with non-resectable hepatocellular carcinoma (HCC), with an estimated end date of December 31, 2026.

Inclusion and Exclusion Criteria

check_circle

Inclusion Criteria

Histological diagnosis of HCC
Life expectancy of at least 12 weeks
Disease which is not amenable to curative surgical or ablation treatment but eligible for locoregional treatment including portal vein invasion Vp1-3. Patients who are candidates for liver transplantation list are eligible at the discretion of the local investigator.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Preserved liver function, as defined by a Child-Pugh score A and B7

cancel

Exclusion Criteria

Diffuse HCC or presence of vascular invasion in the portal vein main stem (Vp4) or extrahepatic spread (including extrahepatic lymph node affection or metastasis) or more than 7 lesions or at least one lesion ≥ 10 cm
Major gastrointestinal bleeding within 4 weeks prior to inclusion
Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
Decompensated liver function as defined by any of the following: Clinically meaningful ascites, hepatic encephalopathy or history of hepatic encephalopathy, Child Pugh ≥8 points. The presence of clinically meaningful ascites is defined as any ascites requiring non-pharmacologic intervention (eg, paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. Subjects on stable doses of diuretics for ascites for ≥2 months are eligible.
Uncontrolled pleural effusion or pericardial effusion
Co-infection of HBV and HCV. Patients with a history of HCV infection but who are negative for HCV RNA by polymerase chain reaction (PCR) will be considered non-infected with HCV.
Prior systemic therapy for HCC (including previous CPI or VEGFi treatment)
Prior treatment with TACE or SIRT if active tumor recurrence is located in previously treated hepatic segment or recurrence within ≤ 6 months after prior TACE or SIRT
Ineligibility for locoregional treatment