An Immuno-therapy Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab or Nivolumab in Combination With Other Agents in Patients With Advanced Liver Cancer

Hepatocellular Carcinoma Clinical Trial

— CheckMate040  

Official title:

A Phase 1/2, Dose-escalation, Open-label, Non-comparative Study of Nivolumab or Nivolumab in Combination With Ipilimumab in Advanced Hepatocellular Carcinoma Subjects With or Without Chronic Viral Hepatitis; and a Randomized, Open-label Study of Nivolumab vs Sorafenib in Advanced Hepatocellular Carcinoma Subjects Who Are Naive to Systemic Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01658878
• Other study ID #: CA209-040
• Secondary ID: 2012-001514-42
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: October 30, 2012
• Est. completion date: June 28, 2024

Study information

• Verified date: December 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The first part of the study is the Dose Escalation Phase designed to establish the safety of nivolumab at different dose levels for each of the three cohorts (uninfected hepatocellular carcinoma (HCC) subjects, hepatitis C virus (HCV)-infected HCC subjects, and hepatitis B virus (HBV)-infected subjects). The second part of the study is the Expansion Phase designed to generate additional clinical data at specified doses for each of the 3 cohorts. A third cohort has been added in this study to compare the efficacy of nivolumab and sorafenib in the treatment of Advanced HCC. A fourth cohort will generate data on the safety and efficacy of the combination nivolumab plus ipilimumab in the treatment of Advanced HCC. In the fifth cohort, additional clinical data will be generated for Child-Pugh B subjects. A Cabozantinib Combination Cohort has been added to evaluate the safety and tolerability of nivolumab in combination with cabozantinib and nivolumab with ipilimumab in combination with cabozantinib.

Description:

Study Classification: Pharmacokinetics/Pharmacodynamics

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 659
• Est. completion date: June 28, 2024
• Est. primary completion date: June 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Subjects of 18 years or older (men and women) with histologically confirmed advanced hepatocellular carcinoma, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and /or locoregional therapies
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
• Dose Escalation Phase: Child-Pugh score of 7 points or less. Cohort 5: Child-Pugh Class B (B7-B8). For all other cohorts Child-Pugh score of 6 points or less

Exclusion Criteria:

• History of autoimmune disease
• Any prior or current clinically significant ascites
• Any history of hepatic encephalopathy

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Biological:
• Nivolumab

Drug:
• Sorafenib

• Ipilimumab

• Cabozantinib

Locations

Country	Name	City	State
Canada	Local Institution - 0065	Halifax	Nova Scotia
Canada	Local Institution - 0022	Montréal	Quebec
Canada	Local Institution - 0039	Toronto	Ontario
France	Local Institution - 0061	Angers
France	Local Institution - 0064	Creteil Cedex
France	Local Institution - 0059	Marseille Cedex 5
France	Local Institution - 0062	Marseille Cedex 9
France	Local Institution - 0042	Paris Cedex 13
France	Local Institution - 0060	Reims Cedex
France	Local Institution - 0058	Vandoeuvre les Nancy
Germany	Local Institution - 0030	Essen
Germany	Local Institution - 0028	Frankfurt
Germany	Local Institution - 0029	Hannover
Germany	Local Institution - 0031	Heidelberg
Hong Kong	Local Institution - 0005	Hong Kong
Hong Kong	Local Institution - 0006	Hong Kong
Italy	Local Institution - 0032	Bologna
Italy	Local Institution - 0056	Firenze
Italy	Local Institution - 0063	Meldola (FC)
Italy	Local Institution - 0055	Milano
Italy	Local Institution - 0034	Napoli
Italy	Local Institution - 0035	Padova
Italy	Local Institution - 0040	Rozzano
Japan	Local Institution - 0036	Kashiwa-shi	Chiba
Japan	Local Institution - 0038	Kurume-shi	Fukuoka
Japan	Local Institution - 0050	Kyoto-shi	Kyoto
Japan	Local Institution - 0037	Osaka-sayama-shi	Osaka
Japan	Local Institution - 0051	Saga
Japan	Local Institution - 0049	Yokohama	Kanagawa
Korea, Republic of	Local Institution - 0016	Seoul
Korea, Republic of	Local Institution - 0021	Seoul
Korea, Republic of	Local Institution - 0026	Seoul
Korea, Republic of	Local Institution - 0066	Seoul
Puerto Rico	Local Institution - 0070	San Juan
Singapore	Local Institution - 0007	Singapore
Singapore	Local Institution - 0009	Singapore
Singapore	Local Institution - 0017	Singapore
Spain	Local Institution - 0019	Barcelona
Spain	Local Institution - 0018	Madrid
Spain	Local Institution - 0020	Madrid
Spain	Local Institution - 0003	Pamplona
Taiwan	Local Institution - 0024	Taipei
Taiwan	Local Institution - 0027	Taipei
Taiwan	Local Institution - 0023	Taoyuan
United Kingdom	Local Institution - 0013	Birmingham	West Midlands
United Kingdom	Local Institution - 0012	Glasgow	Lanarkshire
United Kingdom	Local Institution - 0010	London
United Kingdom	Local Institution - 0011	London	Greater London
United Kingdom	Local Institution - 0014	Manchester	Greater Manchester
United Kingdom	Local Institution - 0015	Wirral	Merseyside
United States	Univ Of Michigan	Ann Arbor	Michigan
United States	Local Institution - 0047	Atlanta	Georgia
United States	Local Institution - 0025	Boston	Massachusetts
United States	Local Institution - 0054	Hackensack	New Jersey
United States	The University Of Texas MD Anderson Cancer Center	Houston	Texas
United States	Local Institution - 0008	Los Angeles	California
United States	Local Institution - 0067	Paterson	New Jersey
United States	Local Institution - 0053	Pensacola	Florida
United States	Local Institution - 0001	Portland	Oregon
United States	Local Institution - 0048	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Puerto Rico,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of nivolumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities		100 days after last dose
Primary	Tolerability of nivolumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities		100 days after last dose
Primary	Objective response rate (ORR) for Expansion phase of nivolumab		Approximately 6 months minimum follow-up
Primary	ORR for Nivolumab vs Sorafenib Cohort		Approximately 6 months minimum follow-up
Primary	Safety of nivolumab plus ipilimumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities		100 days after last dose
Primary	Tolerability of nivolumab plus ipilimumab as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities		100 days after last dose
Primary	ORR for Nivolumab plus Ipilimumab Combination Cohort		Approximately 6 months minimum follow-up
Primary	ORR for Child-Pugh B Cohort		Approximately 6 months minimum follow-up
Primary	Safety of nivolumab plus ipilimumab plus cabozantinib as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities		100 days after last dose
Primary	Tolerability of nivolumab plus ipilimumab plus cabozantinib as evaluated by incidence of adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation, deaths and clinical laboratory test abnormalities		100 days after last dose
Primary	ORR for Nivolumab plus Ipilimumab plus Cabozantinib Combination Cohort		Approximately 6 months minimum follow-up
Secondary	Complete response (CR) Rate	The proportion of subjects whose best overall response (BOR) is CR in the population of interest	Approximately 6 months minimum follow-up
Secondary	Disease control rate (DCR)	The proportion of subjects whose BOR is CR, Partial response (PR) or stable disease (SD) in the population of interest	Approximately 6 months minimum follow-up
Secondary	Duration of response (DOR)	It is defined as time between the date of first radiographic documented objective response and the date of the radiographic disease progression.	Approximately 9 years
Secondary	Time to response (TTR)	It is defined as the time from randomization to the date of the first confirmed CR or PR for the 1L Nivolumab vs Sorafenib Cohort, and from the first dosing date of any study medication to the date of the first confirmed CR or PR for all other cohorts.	Approximately 6 months
Secondary	Time to progression (TTP)	It is defined from the date randomization to the date of the first objectively documented disease progression.	Approximately 9 years
Secondary	TTP Rate	It is defined as the K-M estimated proportion of subjects without progression at select milestones.	Approximately 9 years
Secondary	Progression free survival (PFS)	PFS is defined as the time from randomization date to the date of the first objectively documented tumor progression or death due to any cause	Approximately 9 years
Secondary	Overall survival (OS)	It is defined as the time from date of randomization to the date of death	100 days after last dose
Secondary	Overall survival rate (OSR)	It is defined as the K-M estimated proportion of subjects surviving at select milestones.	100 days after last dose
Secondary	PD-L1 expression		Approximately 6 months
Secondary	Maximum observed serum concentration (Cmax) of nivolumab		Approximately 6 months
Secondary	Time of maximum observed serum concentration (Tmax) of nivolumab		Approximately 6 months
Secondary	Area under the serum concentration time curve in the dosing interval AUC(TAU) of nivolumab		Approximately 6 months
Secondary	Serum concentration achieved at the end of dosing interval (trough concentration) (Ctrough) of nivolumab		Approximately 6 months
Secondary	Serum concentration achieved at the end of the infusion (Ceoinf) of nivolumab		Approximately 6 months
Secondary	Cmax at Cycle 3/ Cmax at Cycle 1 (AI_Cmax) of nivolumab		Approximately 6 months
Secondary	AUC(TAU) at Cycle 3/ AUC(TAU) at Cycle 1 (AI_AUC) of nivolumab		Approximately 6 months
Secondary	Effective T-Half of nivolumab		Approximately 6 months

External Links

•   BMS Clinical Trial Information
•   BMS Clinical Trial Patient Recruiting