Dose Escalation Study of Nivolumab (Anti-PD-1; BMS-936558; ONO-4538) in Patients (Pts) With Advanced Hepatocellular Carcinoma (HCC) With or Without Chronic Viral Hepatitis (Anti-PD-1 HCC)

This study is currently recruiting participants.
Verified March 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01658878
First received: August 3, 2012
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

The purpose of this study is to evaluate the safety, pharmacokinetics, immunoregulatory activity, pharmacodynamics and preliminary anti-tumor activity of BMS-936558 in subjects with advanced hepatocellular carcinoma (HCC)


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 ]
    All non-serious adverse events will be collected from Day 1 until 100 days after the subject's last dose of BMS-936558

  • Incidence of clinical laboratory test abnormalities including hematology and serum chemistry abnormalities [ Time Frame: Up to Week 214 ] [ Designated as safety issue: Yes ]

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: No ]
  • 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 from time zero to the time of the last quantifiable concentration [AUC(0-T)] [ 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: 90
Study Start Date: October 2012
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Non-infected: Nivolumab
Nivolumab 0.3 g/kg or 1 mg/kg or 3 mg/kg or 10 mg/kg intravenous solution, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles /48 doses depending on response
Biological: Nivolumab
Other Name: BMS-936558
Experimental: HCV-infected: Nivolumab
Nivolumab 0.3 g/kg or 1 mg/kg or 3 mg/kg or 10 mg/kg intravenous solution, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles /48 doses depending on response
Biological: Nivolumab
Other Name: BMS-936558
Experimental: HBV-infected: Nivolumab
Nivolumab 0.1 mg/kg or 0.3 g/kg or 1 mg/kg or 3 mg/kg or 10 mg/kg intravenous solution, Every 14 days, 3 doses per each cycle of 42 days, 16 cycles /48 doses depending on response
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 with histological confirmation of advanced hepatocellular carcinoma; subjects must have progressive disease following or be intolerant of at least one line of therapy or refuse sorafenib treatment; subjects must be off sorafenib treatment for at least 28 days prior to first dose
  • Child-Pugh score of B7
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1

Exclusion Criteria:

  • Subjects with brain metastasis
  • Encephalopathy
  • Any prior or current clinically significant ascites as measured by physical examination and that requires active paracentesis 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01658878

Contacts
Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email: Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations
United States, California
Usc Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Contact: Anthony El-Khoueiry, Site 0008         
United States, Michigan
University Of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109-5331
Contact: Theodore Welling, Site 0002         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Contact: Todd Crocenzi, Site 0001         
Hong Kong
Local Institution Recruiting
Hong Kong, Hong Kong
Contact: Site 0006         
Local Institution Recruiting
Hong Kong, Hong Kong, 8525
Contact: Site 0005         
Singapore
Local Institution Recruiting
Singapore, Singapore, 308433
Contact: Site 0007         
Spain
Local Institution Active, not recruiting
Pamplona, Spain, 31192
Sponsors and Collaborators
Bristol-Myers Squibb
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: March 31, 2014
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

Additional relevant MeSH terms:
Carcinoma
Hepatitis
Hepatitis A
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on April 17, 2014