Sequential or Up-front Triple Treatment With Durvalumab, Tremelimumab and Bevacizumab for Non-resectable Hepatocellular Carcinoma (HCC) Patients

Trial Title: Sequential or Up-front Triple Treatment With Durvalumab, Tremelimumab and Bevacizumab for Non-resectable Hepatocellular Carcinoma (HCC) Patients

NCT ID: NCT05844046

Condition: Hepatocellular Carcinoma

Conditions: Official terms:
Carcinoma
Carcinoma, Hepatocellular
Bevacizumab
Durvalumab
Tremelimumab

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Biological
Intervention name: durvalumab, tremelimumab, bevacizumab
Description: durvalumab, tremelimumab and bevacizumab will be administered in the respective arms either as up-front triple treatment or as combined treatment with durvalumab and tremelimumab followed by the addition of bevacizumab
Arm group label: Arm A
Arm group label: Arm B

Summary: This is a randomized, open-label, multi-center, international, Phase II study to assess the efficacy and safety of sequential or up-front triple treatment with durvalumab, tremelimumab and bevacizumab for non-resectable hepatocellular carcinoma. Patients will be randomized in a 1:1 ratio to one of the following arms: Arm A: initial treatment with durvalumab plus tremelimumab followed by treatment escalation with the addition of bevacizumab upon radiological progression or in the absence of objective response Arm B: up-front treatment with durvalumab, tremelimumab and bevacizumab Patients will be stratified according to macrovascular invasion and etiology of liver disease (viral etiologies versus others).

Criteria for eligibility:
Criteria:
KEY INCLUSION CRITERIA Age ≥18 years at the time of study entry Confirmed HCC based on histopathological findings from tumor tissues. Must not have received prior systemic therapy for HCC. Not eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan for the current study. Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C Child-Pugh Score class A ECOG performance status of 0 or 1 at enrollment At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria. Adequate organ and marrow function KEY EXCLUSION CRITERIA Previous study drug(s) assignment in the present study. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 28 days of the first dose of study drug(s). Major surgical procedure or significant traumatic injury within 28 days prior to the first dose of study drug(s), abdominal surgery, abdominal interventions, or significant abdominal traumatic injury within 60 days prior to randomization History of allogeneic organ transplantation (eg, liver transplant). History of hepatic encephalopathy within past 12 months or requirement for medications to prevent or control encephalopathy Clinically meaningful ascites Patients with main portal vein thrombosis (i.e., thrombosis in the main trunk of the portal vein, with or without blood flow) on baseline imaging. Patient currently exhibits symptomatic or uncontrolled hypertension Active or prior documented autoimmune or inflammatory disorders, diverticulitis. Patients without active disease in the last 5 years are excluded unless discussed with the Study Physician and considered appropriate for study participation. Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV). History of another primary malignancy except for the exceptions defined by the study protocol. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC. History of active primary immunodeficiency. Receipt of live attenuated vaccine within 30 days prior to the first dose of study drug(s). Note: Patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s). Major gastrointestinal bleeding within 4 weeks prior to randomization. Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months prior to randomization do not need to repeat the procedure. Those who have received banding and/or sclerotherapy and with no bleeding event within the prior 6 months are eligible provided that a re-endoscopy is performed and that varices remained obliterated, minimal or Grade I Significant vascular disease including aortic aneurysm requiring surgical repair or peripheral arterial thrombosis with 6 months prior to randomization History of abdominal or tracheoesophageal fistula or gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to randomization. Evidence of bleeding diathesis or significant coagulopathy Severe, nonhealing or dehisced wound, active ulcer, or untreated bone fracture Current or recent (within 10 days of randomization) use of acetylsalicyclic acid (=> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol Current or recent (within 10 days prior to randomization) use of fulldose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purpose. Prophylactic use of low molecularweight heparin is allowed. Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy or 180 days after the last dose of durvalumab plus tremelimumab combination therapy or bevacizumab therapy Prior randomization or treatment in a previous durvalumab and/or tremelimumab clinical study regardless of treatment arm assignment.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Hospital of the University of Munich

Address:
City: Munich
Zip: 81377
Country: Germany

Status: Recruiting

Contact:
Last name: Enrico N De Toni, MD

Phone: +49 (0)894400-0
Email: enrico.detoni@med.uni-muenchen.de

Investigator:
Last name: Enrico N De Toni, MD
Email: Principal Investigator

Facility:
Name: Klinikum Rechts der Isar of the Technical University Munich

Address:
City: Munich
Zip: 81675
Country: Germany

Status: Recruiting

Contact:
Last name: Ursula Ehmer, MD

Phone: (0 89) 41 40 - 49 82
Email: ursula.ehmer@mri.tum.de

Contact backup:
Email: ursula.ehmer@mri.tum.de

Facility:
Name: Würzburg University Hospital

Address:
City: Würzburg
Country: Germany

Status: Recruiting

Contact:
Last name: Florian Reiter, MD

Phone: +49 931 201-0
Email: Reiter_F@ukw.de

Contact backup:

Phone: +49 931 201-0
Email: Reiter_F@ukw.de

Start date: April 6, 2023

Completion date: December 31, 2026

Lead sponsor:
Agency: Enrico De Toni
Agency class: Other

Source: Ludwig-Maximilians - University of Munich

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05844046