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

• Conditions: advanced or inoperable hepatocellular carcinoma; MedDRA version: 17.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-006212-38-DE
• Lead Sponsor: Amgen Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-14
• Last Update Posted: 28 September 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Disease Related
• Subjects must have histologically confirmed advanced or inoperable HCC. Biopsy by fine needle aspirate (FNA) is not preferred over a core biopsy but acceptable
• Child-Pugh liver function class A (see Appendix G)
• Measurable disease with at least one unidimensionally measurable lesion per RECIST criteria 1.0 with modifications (see Appendix E).
Demographic
• Men or women = 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Subjects of child-bearing potential and sexually active must consent to the use of an accepted and effective non-hormonal method of contraception (ie, double barrier method [eg, condom plus diaphragm]) from signing the informed consent through 6 months following last administration of study drug
Laboratory
Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days prior to enrollment:
o Hematological function, as follows:
• Absolute neutrophil count (ANC) = 1.5 x 109/L
• Platelet count = 60 x 109/L
• Hemoglobin = 8.5 g/dL
o Renal function, as follows:
• Creatinine clearance > 40 mL/min per 24-hour urine collection or
calculated according to the Cockcroft-Gault formula

(140-age) x actual body weight (kg) ( x 0.85 for
CrCl (mL/min) 72 x serum creatinine (mg/dL) females)

Or

CrCl (140-age) x actual body weight (kg) ( x 0.85 for
(mL/min) 0.8136 x serum creatinine (umol/L) females)

Urinary protein quantitative value of = 30 mg/dL in urinalysis or
=1+ on dipstick, unless quantitative protein is < 1000 mg in a
24 hour urine sample
o Hepatic function, as follows:
• Total bilirubin = 2.0 mg/dL
o Hemostatic function, as follows:
• International Normalized Ratio (INR) = 2.2
General
• Able to tolerate infusions and self-administer oral medications
• Competent to comprehend, sign, and date an institutional review board (IRB)/Independent Ethics Committee (IEC) -approved informed consent form
• Life expectancy = 3 months (per investigator opinion)
• Subject plans to begin protocol directed therapy within 7 days of enrollment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 29
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 31

Exclusion Criteria

Disease Related
• Subject is eligible for liver transplant per investigator’s discretion
• Any previous systemic chemotherapy for HCC (chemotherapy or targeted therapies)
• Previous surgical resections are allowed if = 30 days elapsed prior to enrollment
• Locoregional therapies (eg, TACE) are allowed if = 30 days elapsed prior to enrollment provided that subjects either have a target lesion which has not been subjected to local therapy and/or the target lesions(s) within the field of the local therapy has shown an increase of = 20% in size
• History of arterial or venous thromboembolism within 12 months prior to enrollment
o Subjects with portal vein thrombosis are eligible for this study
except those with main portal vein thrombosis defined as the part of
the portal vein between the inferior vena cava and the first
bifurcation into the left and right vein
• History of clinically significant bleeding within 6 months prior to enrollment (including pulmonary hemorrhage, gastroesophageal varices or gross hemoptysis (= 1/2 teaspoon or 2.5 mL of bright red blood)
• Known history of central nervous system metastases. An MRI or CT scan of the brain or head will be performed within 28 days prior to enrollment.
• Patients with fibrolamellar hepatocellular carcinoma
• Radiation therapy = 14 days prior to enrollment. Subjects who received radiation therapy must have recovered from all radiation induced toxicities prior to enrollment
Medications
• Currently or previously treated with sorafenib or other small molecule inhibitors of VEGF including, but not limited to AMG 706 (motesanib), SU11248 (sunitinib), PTK787 (vatalanib), AZD 2171 (cediranib), AEE-788
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor
• Concomitant or use within 30 days prior to enrollment of any strong inducer of CYP3A4 including, but not limited to, rifampin, St. John’s wort, phenytoin, carbamazepine, phenobarbital and dexamethasone. Dexamethasone as bolus injection or premedication is allowed.
• Concomitant anti-viral therapy is allowed with the exception of interferon alfa or pegylated interferon alfa therapy
• Current or within 30 days prior to enrollment treatment with immune modulators such as systemic cyclosporine and tacrolimus
• Enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trials, or currently receiving other investigational treatments
General Medical
• Known ongoing pancreatitis
• Clinically significant cardiovascular disease within 12 months prior to enrollment, including myocardial infarction, unstable angina, grade 2 or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or arrhythmias not controlled by outpatient medication, percutaneous transluminal coronary angioplasty/stent
• Major surgery within 4 weeks before enrollment or still recovering from prior surgery
• History of allergic reactions to bacterially produced proteins
• Pregnant (ie, positive beta-human chorionic gonadotropin test) or is breast feeding
• Exclude subjects with a history of prior malignancy (see protocol)
• Minor surgical procedures, except placement of tunneled central venous access device (except PICC or peripherally inserted central catheter), or fine needle aspiration within 7 days prior to enrollment
• Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systo

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified