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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT05908786
Registration number
NCT05908786
Ethics application status
Date submitted
7/06/2023
Date registered
18/06/2023
Date last updated
20/05/2024
Titles & IDs
Public title
A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma
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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)
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Secondary ID [1]
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GO44457
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Hepatocellular
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Condition category
Condition code
Cancer
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Non melanoma skin cancer
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Cancer
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Kidney
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Cancer
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Liver
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Intervention/exposure
Study type
Interventional
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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
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Major Pathologic Response (MPR) Rate
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Assessment method [1]
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MPR rate is defined as the proportion of participants with =<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review.
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Timepoint [1]
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At the time of surgery
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Secondary outcome [1]
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Pathologic Complete Response (pCR) Rate
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Assessment method [1]
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pCR rate is defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review.
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Timepoint [1]
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At the time of surgery
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Secondary outcome [2]
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Relapse-Free Survival (RFS)
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Assessment method [2]
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RFS is defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic) according to EASL and/or RECIST v1.1, or death from any cause.
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Timepoint [2]
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Surgery to the first documented recurrence of disease (up to approximately 2 years)
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Secondary outcome [3]
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Event-Free Survival (EFS)
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Assessment method [3]
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EFS is defined as the time from randomization to any of the following events (whichever occurs first): disease progression that precludes surgery, as assessed by the investigator according RECIST v1.1; local regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.
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Timepoint [3]
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Randomization up to approximately 3 years
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Secondary outcome [4]
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Overall Survival (OS)
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Assessment method [4]
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OS is defined as the time from randomization to death from any cause.
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Timepoint [4]
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Randomization to death from any cause (up to approximately 3 years)
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Secondary outcome [5]
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OS Rate at 24 Months
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Assessment method [5]
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OS rate at 24 months is defined as the proportion of participants who have not experience death from any cause at 24 months after randomization.
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Timepoint [5]
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Randomization up to 24 months
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Secondary outcome [6]
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OS Rate at 36 Months
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Assessment method [6]
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OS rate at 36 months is defined as the proportion of participants who have not experience death from any cause at 36 months after randomization.
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Timepoint [6]
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Randomization up to 36 months
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Secondary outcome [7]
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Objective Response Rate (ORR)
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Assessment method [7]
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ORR is defined as the proportion of participants with a radiographic Complete Response (CR) or Partial Response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1 and HCC mRECIST. Responses will be assessed and determined according to RECIST v1.1 and HCC mRECIST but are not required to be confirmed by subsequent imaging assessments.
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Timepoint [7]
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Prior to surgery
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Secondary outcome [8]
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Proportion of Participants Downstaged to Within Milan Criteria
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Assessment method [8]
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Proportion of participants downstaged to within Milan criteria (for participants beyond criteria at randomization). Within Milan criteria is defined as single tumor <= 5 cm or 2 - 3 nodules all <= 3 cm.
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Timepoint [8]
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Prior to surgery
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Secondary outcome [9]
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R0 Resection Rate
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Assessment method [9]
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R0 resection rate (proportion of resected participants obtaining an R0 resection). R0 resection is defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.
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Timepoint [9]
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At the time of surgery
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Secondary outcome [10]
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Percentage of Participants With Adverse Events
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Assessment method [10]
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Timepoint [10]
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Up to approximately 3 years after first participant enrolled
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Secondary outcome [11]
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Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events
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Assessment method [11]
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Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit).
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Timepoint [11]
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>28 days from surgical restaging visit, anticipated up to 56 days
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Secondary outcome [12]
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Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification
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Assessment method [12]
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Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa.
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Timepoint [12]
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Surgery to treatment completion/discontinuation (up to approximately 2 years)
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Secondary outcome [13]
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Post-Operative Mortality
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Assessment method [13]
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Post-operative mortality is defined as death within 90 days after surgery
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Timepoint [13]
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Within 90 days after surgery
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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
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
5/12/2023
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
30/09/2028
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Actual
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Sample size
Target
150
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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United States of America
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State/province [2]
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Colorado
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United States of America
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State/province [3]
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District of Columbia
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United States of America
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Michigan
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United States of America
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New York
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United States of America
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Pennsylvania
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United States of America
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Texas
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United States of America
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Washington
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France
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State/province [9]
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Dijon
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France
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Rennes
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France
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State/province [11]
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Villejuif
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Korea, Republic of
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Gyeonggi-do
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Korea, Republic of
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Seoul
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New Zealand
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Auckland
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Spain
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State/province [15]
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Cantabria
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Spain
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Navarra
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Spain
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Madrid
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Taiwan
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State/province [18]
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Tainan
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Taiwan
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Taipei City
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Taiwan
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Zhongzheng Dist.
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United Kingdom
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Belfast
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United Kingdom
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London
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Hoffmann-La Roche
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate
neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is
designed with the flexibility to open new treatment arms as new agents become available,
close existing treatment arms that demonstrate minimal clinical activity or unacceptable
toxicity, or modify the participant population.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT05908786
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Hoffmann-La Roche
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Reference Study ID Number: GO44457 https://forpatients.roche.com/
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Address
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Phone
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888-662-6728 (U.S. and Canada)
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT05908786
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