A Study of the Effectiveness and Safety of AMG 386 and Sorafenib to Treat Advanced or Inoperable Hepatocellular Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00872014
First received: March 12, 2009
Last updated: June 18, 2013
Last verified: June 2013
  Purpose

The purpose of this study is to determine whether AMG 386, in combination with Sorafenib, is effective in the treatment of advanced or inoperable Hepatocellular cancer in subjects who have not received any prior systemic therapy except surgery or locoregional therapy.

Disease status and disease progression will be assessed every 8 weeks. Subjects will remain on treatment until: progressive disease by RECIST criteria; clinical progression; death or loss to follow-up; or withdrawal of informed consent.


Condition Intervention Phase
Advanced or Inoperable Hepatocellular Carcinoma
Drug: Sorafenib
Drug: AMG 386
Phase 2

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: Phase 2 Open-label Multi-Center Study to Evaluate the Efficacy and Safety of AMG 386 and Sorafenib as First Line Therapy for Subjects With Advanced or Inoperable Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Progression free survival (PFS) rate at 4 months [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events and significant laboratory abnormalities [ Time Frame: Adverse events at every visit, significant laboratory abnormalities at least every 4 weeks ] [ Designated as safety issue: Yes ]
  • Objective response rate, Disease control rate, Progression free survival, Overall survival, Time to progression [ Time Frame: Radiologic imaging every 8 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters for AMG 386 when used in combination with Sorafenib [ Time Frame: Weeks 1, 2, 5, 9, and every 16 weeks thereafter ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameter for Sorafenib when used in combination with AMG 386 [ Time Frame: Weeks 2, 5, 9, and every 16 weeks thereafter ] [ Designated as safety issue: No ]
  • Incidence of the occurrence of anti-AMG 386 antibody formation [ Time Frame: Weeks 1, 5, 9, and every 16 weeks thereafter ] [ Designated as safety issue: No ]
  • Baseline values of and changes from baseline in pharmacodynamic, immunologic, biochemical, transcriptional, pharmacogenetic and angiogenic markers [ Time Frame: Weeks 1, 2, 5, and every 16 weeks thereafter ] [ Designated as safety issue: No ]

Enrollment: 60
Study Start Date: August 2009
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 15mg/ kg cohort
AMG 386 15mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule.
Drug: Sorafenib
AMG 386 is the investigational product administered in this study. Sorafenib will be administered 400mg orally twice daily and indicated for the treatment of advanced or inoperable Hepatocellular Carcinoma. Sorafenib will be administered to all subjects until disease progression, clinical progression, withdrawal of informed consent, unacceptable toxicity or death, whichever comes first.
Drug: AMG 386
AMG 386 will be administered 10mg/kg intravenously once weekly until disease progression, clinical progression, withdrawal of informed consent, unacceptable toxicity or death, whichever comes first.
Other Name: AMG 386 will be administered 15mg/kg intravenously once weekly until disease progression, clinical progression, withdrawal of informed consent, unacceptable tox
Experimental: 10 mg/kg cohort
AMG 386 10mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule.
Drug: Sorafenib
AMG 386 is the investigational product administered in this study. Sorafenib will be administered 400mg orally twice daily and indicated for the treatment of advanced or inoperable Hepatocellular Carcinoma. Sorafenib will be administered to all subjects until disease progression, clinical progression, withdrawal of informed consent, unacceptable toxicity or death, whichever comes first.
Drug: AMG 386
AMG 386 will be administered 10mg/kg intravenously once weekly until disease progression, clinical progression, withdrawal of informed consent, unacceptable toxicity or death, whichever comes first.
Other Name: AMG 386 will be administered 15mg/kg intravenously once weekly until disease progression, clinical progression, withdrawal of informed consent, unacceptable tox

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed advanced or inoperable HCC
  • Child-Pugh A liver function score
  • Measurable disease with at least one unidimensionally measurable lesion per RECIST 1.0 guidelines with modifications
  • Adequate organ and hematological function
  • Men or women greater than or equal to 18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

Exclusion Criteria:

  • Subject is eligible for a liver transplant per investigators discretion
  • Any previous systemic chemotherapy for HCC
  • History of arterial or venous thromboembolism within 12 months prior to enrollment
  • History of clinically significant bleeding within 6 months prior to enrollment
  • History of central nervous system metastases
  • Clinically significant cardiovascular disease within 12 months
  • Uncontrolled hypertension
  • Subjects with a history of prior malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00872014

Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00872014     History of Changes
Other Study ID Numbers: 20080580
Study First Received: March 12, 2009
Last Updated: June 18, 2013
Health Authority: Australia: Human Research Ethics Committee
France:CNOM: National Council of the French Medical Association
Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Liver Neoplasms
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Adenocarcinoma
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 22, 2014