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

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

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.

Trial Description

Primary Outcome:

  • 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
  • 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
  • Objective response rate (ORR) for Expansion phase of nivolumab
  • ORR for Nivolumab vs Sorafenib Cohort
  • 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
  • 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
  • ORR for Nivolumab plus Ipilimumab Combination Cohort
  • ORR for Child-Pugh B Cohort
  • 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
  • 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
  • ORR for Nivolumab plus Ipilimumab plus Cabozantinib Combination Cohort
Secondary Outcome:
  • Complete response (CR) Rate
  • Disease control rate (DCR)
  • Duration of response (DOR)
  • Time to response (TTR)
  • Time to progression (TTP)
  • TTP Rate
  • Progression free survival (PFS)
  • Overall survival (OS)
  • Overall survival rate (OSR)
  • PD-L1 expression
  • Maximum observed serum concentration (Cmax) of nivolumab
  • Time of maximum observed serum concentration (Tmax) of nivolumab
  • Area under the serum concentration time curve in the dosing interval AUC(TAU) of nivolumab
  • Serum concentration achieved at the end of dosing interval (trough concentration) (Ctrough) of nivolumab
  • Serum concentration achieved at the end of the infusion (Ceoinf) of nivolumab
  • Cmax at Cycle 3/ Cmax at Cycle 1 (AI_Cmax) of nivolumab
  • AUC(TAU) at Cycle 3/ AUC(TAU) at Cycle 1 (AI_AUC) of nivolumab
  • Effective T-Half of nivolumab
Study Classification: Pharmacokinetics/Pharmacodynamics

View this trial on ClinicalTrials.gov

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Resources

Canadian Cancer Society

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