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

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05844046

Studienbeginn:
April 2023

Letztes Update:
26.02.2024

Wirkstoff:
durvalumab, tremelimumab, bevacizumab

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Hepatocellular

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Enrico De Toni

Collaborator:
-

Studienlocations
(3 von 3)

Hospital of the University of Munich
81377 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Enrico N De Toni, MD
Phone: +49 (0)894400-0
E-Mail: enrico.detoni@med.uni-muenchen.de» Ansprechpartner anzeigen

Klinikum Rechts der Isar of the Technical University Munich
81675 Munich
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Ursula Ehmer, MD
Phone: (0 89) 41 40 - 49 82
E-Mail: ursula.ehmer@mri.tum.de

E-Mail: ursula.ehmer@mri.tum.de» Ansprechpartner anzeigen

Würzburg University Hospital
Würzburg
(Bayern)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Florian Reiter, MD
Phone: +49 931 201-0
E-Mail: Reiter_F@ukw.de

Phone: +49 931 201-0
E-Mail: Reiter_F@ukw.de» Ansprechpartner anzeigen

Studien-Informationen

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).

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. ORR (Time Frame - 24 months):
overall response rate

Secondary outcome:

1. mOS (Time Frame - 24 months):
median overall survival

2. PFS (Time Frame - 24 months):
Progression-free survival

3. TTP (Time Frame - 24 months):
Time to progression

4. ORR-BICR (Time Frame - 24 months):
Objective response rate acc. to BICR

Studien-Arme

Experimental: Arm A
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.
Experimental: Arm B
Durvalumab plus tremelimumab followed by maintenance treatment with durvalumab and bevacizumab.

Geprüfte Regime

durvalumab, tremelimumab, bevacizumab:
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

Quelle: ClinicalTrials.gov

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