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Hepatocellular CarcinomaPhase 2MONTBLANCNCT05844046

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

A Phase 2 study testing durvalumab, tremelimumab, bevacizumab in people with Hepatocellular Carcinoma, run by Enrico De Toni at 3 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatocellular Carcinoma
What is being tested?
durvalumab, tremelimumab, bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
83 participants
Where
3 sitesGermany
Study dates
6 Apr 2023to 31 Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 9Show fewer
  • 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

Who cannot join

  • 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
Show all 25Show fewer
  • 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.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Germany3 sites, 3 recruiting

  • Hospital of the University of Munich

    Munich, 81377

    Enrico N De Toni, MD, +49 (0)894400-0, enrico.detoni@med.uni-muenchen.de

    Enrico N De Toni, MD

    Recruiting

  • Klinikum Rechts der Isar of the Technical University Munich

    Munich, 81675

    Ursula Ehmer, MD, (0 89) 41 40 - 49 82, ursula.ehmer@mri.tum.de

    ursula.ehmer@mri.tum.de

    Recruiting

  • Würzburg University Hospital

    Würzburg

    Florian Reiter, MD, +49 931 201-0, Reiter_F@ukw.de

    +49 931 201-0, Reiter_F@ukw.de

    Recruiting

Other trials in Germany

About this study

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

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:

Read more

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).

Being tested
durvalumab, tremelimumab, bevacizumab
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • durvalumab, tremelimumab, bevacizumabBiological

    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

Study groups in NCT05844046
Study groupRoleWhat they receive
Arm AExperimentalDurvalumab (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.
Receives: Biological: durvalumab, tremelimumab, bevacizumab
Arm BExperimentalDurvalumab plus tremelimumab followed by maintenance treatment with durvalumab and bevacizumab.
Receives: Biological: durvalumab, tremelimumab, bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ORR

    overall response rate

    Measured: 24 months

Secondary outcomes (4)

  1. mOS

    median overall survival

    Measured: 24 months

  2. PFS

    Progression-free survival

    Measured: 24 months

  3. TTP

    Time to progression

    Measured: 24 months

  4. ORR-BICR

    Objective response rate acc. to BICR

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 May 2023
  2. Study start6 Apr 2023
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
83 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05844046
Sponsor's protocol ID
MONTBLANC
Other IDs
2022-001201-48
Acronym
MONTBLANC
Status last verified
Jul 2024
First submitted
11 Apr 2023
Last updated
16 Jul 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 38643505

  • Ben Khaled N, Ehmer U, Kubisch I, Gonzalez-Carmona MA, Philipp A, Seidensticker M, Altenhofer J, Basch M, Huwer T, Oehrle B, Geier A, Solda C, Auriemma A, Bauer U, Zhou T, Perkhofer L, Chater J, Weinmann A, von Felden J, De Rosa A, Vivaldi C, Piseddu I, Schwald I, Enssle S, Karin M, Schneider JS, Groper MN, Ondrejkova K, Weiss L, Beyer G, Schulze K, Antonuzzo L, Masi G, Daniele B, Ricke J, Mayerle J, Foerster F, Reiter FP, Ettrich TJ, De Toni EN. Sequential or upfront triple combination with durvalumab, tremelimumab, and bevacizumab for patients with unresectable hepatocellular carcinoma: the MONTBLANC trial protocol (AIO-HEP-0325/ass). Ther Adv Med Oncol. 2026 Feb 20;18:17588359261417640. doi: 10.1177/17588359261417640. eCollection 2026.

    PubMed 41732658

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing durvalumab, tremelimumab, bevacizumab in people with Hepatocellular Carcinoma, run by Enrico De Toni at 3 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 16 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05844046, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2024.

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