Phase 2, Open-label Single-Arm, 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.
- Conditions
- advanced or inoperable hepatocellular carcinomaMedDRA version: 9.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable
- Registration Number
- EUCTR2008-006212-38-FR
- Lead Sponsor
- Amgen Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
Disease Related
• Subjects must have histologically confirmed advanced or inoperable HCC
• Child-Pugh liver function class A (see Appendix G)
• Measurable disease with at least one unidimensionally measurable lesion per RECIST (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 = 75 x 109/L
• Hemoglobin = 8.5 g/dL
o Renal function, as follows:
• Calculated creatinine clearance > 50 mL/min according to the Cockcroft-Gault formula
• Urinary protein quantitative value of = 30 mg in urinalysis or
= 1+ on dipstick, unless quantitative protein is < 1000 mg in a 24 hour urine sample
o Hepatic function, as follows:
• Aspartate aminotransferase (AST) = 5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) = 5 x ULN
• Alkaline phosphatase = 2.0 x ULN (if bone metastases are present, = 5 x ULN)
• Albumin = 2.8 g/dL
• Bilirubin = 2.0 mg/dL
o Hemostatic function, as follows:
• International Normalized Ratio (INR) = 1.7
• Partial thromboplastin time (PTT) or activated partial thromboplastin (aPTT) = 1.5 x ULN per institutional laboratory range
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
Disease Related
• 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
• 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 30 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 including but not limited to, XL-820, XL-184, or CVX-060/PF-4856884
• 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
• 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 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, except:
- Malignancy treated with curative intent and with no known active disease
present for = 3 years before enrollment and felt to be at low risk for recurrence by treating physician
- Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
- Adequately treated cervical carcinoma in situ without evidence of disease
- Prostatic intraepithelial neoplasia without evidence of prostate cancer
- Other primary solid tumor with no known active disease present that in the opinion of the investigator will not affect patient outcome in the setting of current hepatocellular carcinoma diagnosis
•
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method