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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 (CheckMate040)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01658878
Recruitment Status : Active, not recruiting
First Posted : August 7, 2012
Last Update Posted : December 14, 2023
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Description
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Brief 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.


Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Biological: Nivolumab Drug: Sorafenib Drug: Ipilimumab Drug: Cabozantinib Phase 1 Phase 2

Detailed Description:
Study Classification: Pharmacokinetics/Pharmacodynamics
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 659 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 30, 2012
Estimated Primary Completion Date : June 28, 2024
Estimated Study Completion Date : June 28, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Non-infected: Nivolumab
Nivolumab intravenous solution on specific days
 Biological: Nivolumab
Other Name: BMS-936558
Experimental: HCV-infected: Nivolumab
Nivolumab intravenous solution on specific days
 Biological: Nivolumab
Other Name: BMS-936558
Experimental: HBV-infected: Nivolumab
Nivolumab intravenous solution on specific days
 Biological: Nivolumab
Other Name: BMS-936558
Experimental: Nivolumab
Nivolumab intravenous solution on specific days
 Biological: Nivolumab
Other Name: BMS-936558
Active Comparator: Sorafenib
Sorafenib tablets on specific days
 Drug: Sorafenib
Experimental: Nivolumab plus Ipilimumab Combination
Nivolumab intravenous solution + Ipilimumab intravenous solution on specific days
 Biological: Nivolumab
Other Name: BMS-936558

Drug: Ipilimumab
Experimental: Child-Pugh B
Nivolumab intravenous solution on specific days
 Biological: Nivolumab
Other Name: BMS-936558
Experimental: Nivolumab plus Cabozantinib Combination
Nivolumab intravenous solution + cabozantinib oral tablets on specific days
 Drug: Cabozantinib
Experimental: Nivolumab plus Ipilimumab plus Cabozantinib
Nivolumab intravenous solution + Ipilimumab intravenous solution + cabozantinib oral tablets on specific days
 Drug: Cabozantinib


Outcome Measures
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Primary Outcome Measures :
  1. 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 [ Time Frame: 100 days after last dose ]
  2. 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 [ Time Frame: 100 days after last dose ]
  3. Objective response rate (ORR) for Expansion phase of nivolumab [ Time Frame: Approximately 6 months minimum follow-up ]
  4. ORR for Nivolumab vs Sorafenib Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  5. 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 [ Time Frame: 100 days after last dose ]
  6. 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 [ Time Frame: 100 days after last dose ]
  7. ORR for Nivolumab plus Ipilimumab Combination Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  8. ORR for Child-Pugh B Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  9. 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 [ Time Frame: 100 days after last dose ]
  10. 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 [ Time Frame: 100 days after last dose ]
  11. ORR for Nivolumab plus Ipilimumab plus Cabozantinib Combination Cohort [ Time Frame: Approximately 6 months minimum follow-up ]

Secondary Outcome Measures :
  1. Complete response (CR) Rate [ Time Frame: Approximately 6 months minimum follow-up ]
    The proportion of subjects whose best overall response (BOR) is CR in the population of interest

  2. Disease control rate (DCR) [ Time Frame: Approximately 6 months minimum follow-up ]
    The proportion of subjects whose BOR is CR, Partial response (PR) or stable disease (SD) in the population of interest

  3. Duration of response (DOR) [ Time Frame: Approximately 9 years ]
    It is defined as time between the date of first radiographic documented objective response and the date of the radiographic disease progression.

  4. Time to response (TTR) [ Time Frame: Approximately 6 months ]
    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.

  5. Time to progression (TTP) [ Time Frame: Approximately 9 years ]
    It is defined from the date randomization to the date of the first objectively documented disease progression.

  6. TTP Rate [ Time Frame: Approximately 9 years ]
    It is defined as the K-M estimated proportion of subjects without progression at select milestones.

  7. Progression free survival (PFS) [ Time Frame: Approximately 9 years ]
    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

  8. Overall survival (OS) [ Time Frame: 100 days after last dose ]
    It is defined as the time from date of randomization to the date of death

  9. Overall survival rate (OSR) [ Time Frame: 100 days after last dose ]
    It is defined as the K-M estimated proportion of subjects surviving at select milestones.

  10. PD-L1 expression [ Time Frame: Approximately 6 months ]
  11. Maximum observed serum concentration (Cmax) of nivolumab [ Time Frame: Approximately 6 months ]
  12. Time of maximum observed serum concentration (Tmax) of nivolumab [ Time Frame: Approximately 6 months ]
  13. Area under the serum concentration time curve in the dosing interval AUC(TAU) of nivolumab [ Time Frame: Approximately 6 months ]
  14. Serum concentration achieved at the end of dosing interval (trough concentration) (Ctrough) of nivolumab [ Time Frame: Approximately 6 months ]
  15. Serum concentration achieved at the end of the infusion (Ceoinf) of nivolumab [ Time Frame: Approximately 6 months ]
  16. Cmax at Cycle 3/ Cmax at Cycle 1 (AI_Cmax) of nivolumab [ Time Frame: Approximately 6 months ]
  17. AUC(TAU) at Cycle 3/ AUC(TAU) at Cycle 1 (AI_AUC) of nivolumab [ Time Frame: Approximately 6 months ]
  18. Effective T-Half of nivolumab [ Time Frame: Approximately 6 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01658878


Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01658878    
Other Study ID Numbers: CA209-040
2012-001514-42 ( EudraCT Number )
First Posted: August 7, 2012    Key Record Dates
Last Update Posted: December 14, 2023
Last Verified: December 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
 Liver Diseases
Nivolumab
Ipilimumab
Sorafenib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors