Study to Evaluate the Effectiveness, Safety and Tolerability of Nivolumab in Subjects With Advanced Liver Cancer Anti-PD-1 HCC (Anti-Programmed-Death-1 Hepatocellular Carcinoma)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 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: August 19, 2015
Last verified: May 2015
  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 HCC subjects, HCV-infected HCC subjects, and 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.


Condition Intervention Phase
Hepatocellular Carcinoma
Biological: Nivolumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Dose Escalation Study to Investigate the Safety, Immunoregulatory Activity, Pharmacokinetics, and Preliminary Antitumor Activity of Anti-Programmed-Death-1 (PD-1) Antibody (BMS-936558) in Advanced Hepatocellular Carcinoma in Subjects With or Without Chronic Viral Hepatitis

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Incidence of worst adverse events [ Time Frame: Up to 100 days after the last dose of BMS-936558 ] [ Designated as safety issue: Yes ]
    Incidence of worst adverse events: all adverse events collected from Day 1 until 100 days after the subject's last dose of nivolumab

  • Incidence of clinical laboratory test abnormalities including hematology and serum chemistry abnormalities [ Time Frame: collected from Day 1 until 100 days after the subject's last dose of nivolumab ] [ Designated as safety issue: Yes ]
    Incidence of clinical laboratory test abnormalities: collected from Day 1 until 100 days after the subject's last dose of nivolumab


Secondary Outcome Measures:
  • Objective response rate and disease control rate [ Time Frame: Up to Week 214 ] [ Designated as safety issue: No ]
  • Frequency of subjects with increase in anti-drug antibodies (ADA) levels [ Time Frame: Up to Week 214 ] [ Designated as safety issue: Yes ]
  • Geometric means and coefficients of variation for the pharmacokinetic parameter of serum concentration achieved at the end of the dosing interval (trough concentration, Cmin) [ Time Frame: Up to Week 214 ] [ Designated as safety issue: No ]
  • Geometric means and coefficients of variation for the pharmacokinetic parameter of maximum observed serum concentration (Cmax) [ Time Frame: Up to Week 214 ] [ Designated as safety issue: No ]
  • Geometric means and coefficients of variation for the pharmacokinetic parameter of serum concentration achieved at the end of the infusion (Ceoinf) [ Time Frame: Up to Week 214 ] [ Designated as safety issue: No ]
  • Geometric means and coefficients of variation for the pharmacokinetic parameter of area under the concentration-time curve in one dosing interval [AUC(TAU)] [ Time Frame: Up to Week 214 ] [ Designated as safety issue: No ]
  • Medians, minimum, and maximum for the pharmacokinetic parameter of time to maximum observed concentration (Tmax) [ Time Frame: Up to Week 214 ] [ Designated as safety issue: No ]

Estimated Enrollment: 270
Study Start Date: September 2012
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2018 (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

Detailed Description:

Study Classification: Pharmacokinetics/Pharmacodynamics

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 histological confirmation of advanced hepatocellular carcinoma
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • For the dose escalation cohorts (uninfected, HCV-infected, and HBV-infected): subjects must have progressive disease following or be intolerant of at least one line of systemic therapy or refuse sorafenib treatment
  • For the uninfected sorafenib naive or intolerant HCC expansion cohort, subjects must either never have received sorafenib treatment or were intolerant to sorafenib therapy
  • For the uninfected sorafenib failure HCC expansion cohort, subjects must have had documented radiographic or symptomatic progression during or after sorafenib therapy
  • Dose Escalation Phase: Child-Pugh score of 7 points or less, i.e., Child-Pugh A or Child Pugh B7
  • Expansion Phase: Child-Pugh score of 6 points or less, i.e., Child-Pugh A

Exclusion Criteria:

  • Subjects with brain metasteses
  • Any prior or current clinically significant ascites as measured by physical examination and that requires active parancentesis for control
  • Any history of clinically meaningful variceal bleeding within the last three months
  • Active coinfection with both hepatitis B and C
  • Hepatitis D infection in subjects with hepatitis B
  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 44 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:
No publications provided

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: August 19, 2015
Health Authority: United States: Food and Drug Administration
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Singapore: Health Sciences Authority
Hong Kong: Department of Health
Canada: Health Canada
Germany: Paul-Ehrlich-Institut
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Italy: The Italian Medicines Agency
Japan: Pharmaceuticals and Medical Devices Agency
Korea: Food and Drug Administration
Taiwan : Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on August 31, 2015