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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05908786




Registration number
NCT05908786
Ethics application status
Date submitted
7/06/2023
Date registered
18/06/2023

Titles & IDs
Public title
A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma
Scientific title
A Phase Ib/II, Open-Label, Multicenter, Randomized Platform Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (MORPHEUS-NEO HCC)
Secondary ID [1] 0 0
GO44457
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney
Cancer 0 0 0 0
Liver

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Bevacizumab
Treatment: Drugs - Tiragolumab
Treatment: Drugs - Tobemstomig

Experimental: Atezo + Bev - Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Experimental: Atezo + Bev +Tira - Participants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Experimental: Tobe + Bev - Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.


Treatment: Drugs: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.

Treatment: Drugs: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

Treatment: Drugs: Tiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.

Treatment: Drugs: Tobemstomig
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Major Pathologic Response (MPR) Rate
Timepoint [1] 0 0
At the time of surgery
Secondary outcome [1] 0 0
Pathologic Complete Response (pCR) Rate
Timepoint [1] 0 0
At the time of surgery
Secondary outcome [2] 0 0
Relapse-Free Survival (RFS)
Timepoint [2] 0 0
Surgery to the first documented recurrence of disease (up to approximately 2 years)
Secondary outcome [3] 0 0
Event-Free Survival (EFS)
Timepoint [3] 0 0
Randomization up to approximately 3 years
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
Randomization to death from any cause (up to approximately 3 years)
Secondary outcome [5] 0 0
OS Rate at 24 Months
Timepoint [5] 0 0
Randomization up to 24 months
Secondary outcome [6] 0 0
OS Rate at 36 Months
Timepoint [6] 0 0
Randomization up to 36 months
Secondary outcome [7] 0 0
Objective Response Rate (ORR)
Timepoint [7] 0 0
Prior to surgery
Secondary outcome [8] 0 0
Proportion of Participants Downstaged to Within Milan Criteria
Timepoint [8] 0 0
Prior to surgery
Secondary outcome [9] 0 0
R0 Resection Rate
Timepoint [9] 0 0
At the time of surgery
Secondary outcome [10] 0 0
Percentage of Participants With Adverse Events
Timepoint [10] 0 0
Up to approximately 3 years after first participant enrolled
Secondary outcome [11] 0 0
Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events
Timepoint [11] 0 0
>28 days from surgical restaging visit, anticipated up to 56 days
Secondary outcome [12] 0 0
Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification
Timepoint [12] 0 0
Surgery to treatment completion/discontinuation (up to approximately 2 years)
Secondary outcome [13] 0 0
Post-Operative Mortality
Timepoint [13] 0 0
Within 90 days after surgery

Eligibility
Key inclusion criteria
* Diagnosis of HCC confirmed either histologically or clinically according to AASLD criteria for patients with cirrhosis. For participants without cirrhosis, histological confirmation is mandatory.
* HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant. Patients presenting with resectable HCC within or beyond Milan criteria (without extrahepatic spread or macrovascular invasion) are eligible.
* Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
* Child-Pugh Class A within 7 days prior to randomization
* Negative HIV test at screening
* No prior locoregional or systemic treatment for HCC
* Adequate hematologic and end-organ function
* Documented virology status of hepatitis
* For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
* For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm

General
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Presence of extrahepatic disease or macrovascular invasion
* Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC
* History of hepatic encephalopathy if clinically significant within one year prior to initiation of study treatment
* Moderate or severe ascites
* Active co-infection with HBV and HCV
* Known active co-infection with HBV and hepatitis D viral infection
* Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
* Treatment with investigational therapy within 28 days prior to initiation of study treatment
* Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
* A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
* Inadequately controlled hypertension
* History of hypertensive crisis or hypertensive encephalopathy
* Significant vascular disease within 6 months prior to initiation of study treatment
* History of hemoptysis within 1 month prior to initiation of study treatment
* Evidence of bleeding diathesis or significant coagulopathy
* Current or recent (<= 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
* History of abdominal or tracheoesophageal fistula, GI perforation or intra-abdominal abscesses within 6 months prior to initiation of study treatment
* History of intestinal obstruction and/or clinical sign or symptoms of GI obstruction
* Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
* Grade >= proteinuria
* Major surgical procedure, open biopsy, or significant traumatic injury, or abdominal surgery, interventions or traumatic injuries, or anticipation of need of major surgical procedure other than potentially curative liver resection
* Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
* Serious infection requiring oral or IV antibiotics and/or hospitalization
* Active tuberculosis

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/12/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/09/2028
Actual
Sample size
Target
150
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Washington
Country [9] 0 0
Austria
State/province [9] 0 0
Klagenfurt am Worthersee
Country [10] 0 0
France
State/province [10] 0 0
Dijon
Country [11] 0 0
France
State/province [11] 0 0
Rennes
Country [12] 0 0
France
State/province [12] 0 0
Villejuif
Country [13] 0 0
Germany
State/province [13] 0 0
Mainz
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Gyeonggi-do
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
New Zealand
State/province [16] 0 0
Auckland
Country [17] 0 0
Spain
State/province [17] 0 0
Cantabria
Country [18] 0 0
Spain
State/province [18] 0 0
Navarra
Country [19] 0 0
Spain
State/province [19] 0 0
Barcelona
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
Taiwan
State/province [21] 0 0
Tainan
Country [22] 0 0
Taiwan
State/province [22] 0 0
Taipei City
Country [23] 0 0
Taiwan
State/province [23] 0 0
Zhongzheng Dist.
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Belfast
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Reference Study ID Number: GO44457 https://forpatients.roche.com/
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. and Canada)
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05908786