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A Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab and the Combination Nivolumab Plus Ipilimumab in Patients With Advanced Liver Cancer (CheckMate040)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Bristol-Myers Squibb
Sponsor:
Collaborator:
Ono Pharmaceutical Co. Ltd
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01658878
First received: August 3, 2012
Last updated: February 16, 2017
Last verified: August 2016
  Purpose

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.


Condition Intervention Phase
Hepatocellular Carcinoma
Biological: Nivolumab
Drug: Sorafenib
Drug: Ipilimumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • 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 ]
  • 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 ]
  • Objective response rate (ORR) for Expansion phase of nivolumab [ Time Frame: Approximately 6 months minimum follow-up ]
  • ORR for Nivolumab vs Sorafenib Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  • 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 ]
  • 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 ]
  • ORR for Nivolumab plus Ipilimumab Combination Cohort [ Time Frame: Approximately 6 months minimum follow-up ]
  • ORR for Child-Pugh B Cohort [ Time Frame: Approximately 6 months minimum follow-up ]

Secondary Outcome Measures:
  • 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

  • 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

  • Duration of response (DOR) [ Time Frame: at the time of last dose ]
    It is defined as time between the date of first radiographic documented objective response and the date of the radiographic disease progression.

  • 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.

  • Time to progression (TTP) [ Time Frame: At the time of last dose ]
    It is defined from the date randomization to the date of the first objectively documented disease progression.

  • TTP Rate [ Time Frame: At the time of last dose ]
    It is defined as the K-M estimated proportion of subjects without progression at select milestones.

  • Progression free survival (PFS) [ Time Frame: At the time of last dose ]
    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

  • 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

  • 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.

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

Estimated Enrollment: 620
Study Start Date: September 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

Detailed Description:
Study Classification: Pharmacokinetics/Pharmacodynamics
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01658878

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

  Show 60 Study Locations
Sponsors and Collaborators
Bristol-Myers Squibb
Ono Pharmaceutical Co. Ltd
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01658878     History of Changes
Other Study ID Numbers: CA209-040  2012-001514-42 
Study First Received: August 3, 2012
Last Updated: February 16, 2017

Additional relevant MeSH terms:
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
Sorafenib
Nivolumab
Niacinamide
Antibodies, Monoclonal
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Immunologic Factors

ClinicalTrials.gov processed this record on February 23, 2017