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

Sponsor

Amgen (Industry)

Overall Status

Completed

CT.gov ID

NCT00872014

Collaborator

(none)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Advanced Hepatocellular Carcinoma Inoperable Hepatocellular Carcinoma	Drug: AMG 386 Drug: AMG 386 Drug: Sorafenib	Phase 2

Detailed Description

The primary objective is to evaluate the efficacy of AMG 386 in combination with sorafenib as measured by the progression free survival (PFS) rate at 4 months in subjects with advanced or inoperable hepatocellular carcinoma (HCC).

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

Aug 1, 2009

Actual Primary Completion Date :

Oct 1, 2011

Actual Study Completion Date :

Jun 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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: AMG 386 Two doses of AMG 386 (15 mg/kg) IV QW will be studied Drug: Sorafenib Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort
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: AMG 386 Two doses of AMG 386 (10 mg/kg) IV QW will be studied Drug: Sorafenib Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort

Arm

Intervention/Treatment

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: AMG 386

Two doses of AMG 386 (15 mg/kg) IV QW will be studied

Drug: Sorafenib

Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort

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: AMG 386

Two doses of AMG 386 (10 mg/kg) IV QW will be studied

Drug: Sorafenib

Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort

Outcome Measures

Primary Outcome Measures

Progression free survival (PFS) rate at 4 months [4 months]

Secondary Outcome Measures

Incidence of adverse events and significant laboratory abnormalities [Adverse events at every visit, significant laboratory abnormalities at least every 4 weeks]
Objective response rate, Disease control rate, Progression free survival, Overall survival, Time to progression [Radiologic imaging every 8 weeks]
Pharmacokinetic parameters for AMG 386 when used in combination with Sorafenib [Weeks 1, 2, 5, 9, and every 16 weeks thereafter]
Pharmacokinetic parameter for Sorafenib when used in combination with AMG 386 [Weeks 2, 5, 9, and every 16 weeks thereafter]
Incidence of the occurrence of anti-AMG 386 antibody formation [Weeks 1, 5, 9, and every 16 weeks thereafter]
Baseline values of and changes from baseline in pharmacodynamic, immunologic, biochemical, transcriptional, pharmacogenetic and angiogenic markers [Weeks 1, 2, 5, and every 16 weeks thereafter]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

No locations specified.

Sponsors and Collaborators

Amgen

Investigators

Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

AmgenTrials clinical trials website

Publications

None provided.

Responsible Party:

Amgen

ClinicalTrials.gov Identifier:

NCT00872014

Other Study ID Numbers:

20080580

First Posted:

Mar 30, 2009

Last Update Posted:

Apr 4, 2016

Last Verified:

Feb 1, 2016

Additional relevant MeSH terms:

Carcinoma

Carcinoma, Hepatocellular

Sorafenib

Trebananib

Study Results

No Results Posted as of Apr 4, 2016