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

NCT05844046 | Recruiting Phase 2 DMC

• 2 other identifiers: MONTBLANC2022-001201-48
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 3

Brief 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).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• ORR

  overall response rate

  24 months

Secondary Outcomes (4)

• mOS

  24 months

• PFS

  24 months

• TTP

  24 months

• ORR-BICR

  24 months

Other Outcomes (9)

• DOR

  24 months

• DCR

  24 months

• OS-18m

  18 months

Study Arms (2)

Arm A

EXPERIMENTAL

Durvalumab (1500 mg q4w) plus tremelimumab (300 mg x 1) followed by addition of bevacizumab (15mg/kg) upon detection of radiological progression or in the absence of objective response after the second staging.

Biological: durvalumab, tremelimumab, bevacizumab

Arm B

EXPERIMENTAL

Durvalumab plus tremelimumab followed by maintenance treatment with durvalumab and bevacizumab.

Biological: durvalumab, tremelimumab, bevacizumab

Interventions

durvalumab, tremelimumab, bevacizumab BIOLOGICAL

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 A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Enrico De Toni: lead

Study Sites (3)

Hospital of the University of Munich

Munich, 81377, Germany

RECRUITING

Klinikum Rechts der Isar of the Technical University Munich

Munich, 81675, Germany

RECRUITING

Würzburg University Hospital

Würzburg, Germany

RECRUITING

Related Publications (1)

• De Toni EN, Mayerle J, Oehrle B, Seidensticker M, Rimassa L, Philipp A, Roessler D, Khaled NB. Letter: Presence of progression or absence of response? Alternative trial designs for immunotherapy of advanced hepatocellular carcinoma. Aliment Pharmacol Ther. 2024 Jun;59(11):1462-1464. doi: 10.1111/apt.17985. Epub 2024 Apr 21. No abstract available.

  PMID: 38643505 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; tremelimumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. Dr. Enrico De Toni

Study Record Dates

• First Submitted: April 11, 2023
• First Posted: May 6, 2023
• Study Start: April 6, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 16, 2024

Record last verified: 2024-07

Locations

DE (3)