Clinical trial NCT05908786: A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma
Official 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-06-18
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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

Primary outcomes:
measure: Major Pathologic Response (MPR) Rate
timeFrame: At the time of surgery
Secondary outcomes:
measure: Pathologic Complete Response (pCR) Rate
timeFrame: At the time of surgery
measure: Relapse-Free Survival (RFS)
timeFrame: Surgery to the first documented recurrence of disease (up to approximately 2 years)
measure: Event-Free Survival (EFS)
timeFrame: Randomization up to approximately 3 years
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause (up to approximately 3 years)
measure: OS Rate at 24 Months
timeFrame: Randomization up to 24 months
measure: OS Rate at 36 Months
timeFrame: Randomization up to 36 months
measure: Objective Response Rate (ORR)
timeFrame: Prior to surgery
measure: Proportion of Participants Downstaged to Within Milan Criteria
timeFrame: Prior to surgery
measure: R0 Resection Rate
timeFrame: At the time of surgery
measure: Percentage of Participants With Adverse Events
timeFrame: Up to approximately 3 years after first participant enrolled
measure: Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events
timeFrame: >28 days from surgical restaging visit, anticipated up to 56 days
measure: Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification
timeFrame: Surgery to treatment completion/discontinuation (up to approximately 2 years)
measure: Post-Operative Mortality
timeFrame: Within 90 days after surgery
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of Southern California (USC)
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA) - Cancer Care - Santa Monica
state: California
city: New Haven
country: United States
facility: Yale School of Medicine - Smilow Cancer Hospital - Yale-New Haven Hospital Location
state: Colorado
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
state: Michigan
city: Bronx
country: United States
facility: Montefiore Einstein Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson/University of Washington Cancer Consortium
state: Washington
city: Klagenfurt am Worthersee
country: Austria
facility: Klinikum Klagenfurt am Wörthersee
city: Vienna
country: Austria
facility: Wiener Gesundheitsverbund, Klinik Favoriten
city: Vienna
country: Austria
facility: Department of Internal Medicine III AKH and Medical University of Vienna
city: Dijon
country: France
facility: Centre Georges Francois Leclerc (CGFL)
city: Rennes
country: France
facility: Centre Eugene Marquis (CEM)
city: Villejuif CEDEX
country: France
facility: Gustave Roussy
city: Villejuif
country: France
facility: Assistance Publique-Hopitaux de Paris
city: Essen
country: Germany
facility: University Essen
city: Frankfurt
country: Germany
facility: Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin
city: Mainz
country: Germany
facility: Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
city: Gyeonggi-do
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Auckland
country: New Zealand
facility: Auckland District Health Board (ADHB)
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona (Hospital Clinic i Provincial)
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz.
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Tainan
country: Taiwan
facility: Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Zhongzheng Dist.
country: Taiwan
facility: National Taiwan University Hospital (NTUH) - Cancer Research Center
city: Belfast
country: United Kingdom
facility: Belfast Health and Social Care Trust - Belfast City Hospital
city: London
country: United Kingdom
facility: Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: