AMG 386, 20060159 Phase 2, RCC 1st Line in Combination With Sorafenib
- Conditions
- Subjects with Metastatic Clear Cell Carcinoma of the KidneyMedDRA version: 14.0Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2007-000147-98-BE
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
Disease Related:
• Subjects must have a histologically confirmed metastatic RCC with a clear cell component
• Low or intermediate risk according to the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk classification defined as meeting between 0 and 2 of the following risk factors:
- Karnofsky performance status < 80%
- Serum lactate dehydrogenase > 1.5 x upper limit of normal (ULN)
- Serum hemoglobin < lower limit of normal (LLN) for their institutions
- Serum Calcium (corrected) > 10 mg/dL
- Time from diagnosis of RCC to first systemic treatment < 1 year
• Measurable disease with at least one unidimensionally measurable lesion per RECIST.
Complete radiology and tumor measurement within 28 days prior to
randomization:
o Chest: CT / MRI scan with intravenous contrast if the contrast is not
medically contraindicated
o Abdomen: CT / MRI scan with intravenous contrast if the contrast is
not medically contraindicated
o Pelvis: CT / MRI scan with intravenous contrast if the contrast is not
medically contraindicated
o Brain or Head: CT / MRI scan
o Bone: Whole body Bone Scintigraphy
Demographic:
• Men or women= 18 years old
Laboratory:
• Adequate organ and hematological function as evidenced by the following laboratory studies within 14 days of randomization:
• Hematological function, as follows:
- Absolute neutrophil count (ANC) = 1.5 x 10e9/L
- Platelet count = 100 x 10e9/L
- Hemoglobin=9 g/dL
• 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
• Hepatic function, as follows:
- Aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN) (if liver metastases are present, = 5 x ULN)
- Alanine aminotransferase (ALT) = 2.5 x ULN (if liver metastases are present, = 5 x ULN)
- Alkaline phosphatase = 2.0 x ULN (if bone or liver metastases are present, = 5 x ULN)
- Bilirubin= 2.0 x ULN
• Hemostatic function, as follows:
- International Normalized Ratio (INR) < 1.5 per institutional laboratory range
- 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) or
Independent Ethics Committee (IEC) -approved informed consent form
• ECOG of 0 or 1
• Subject plans to begin protocol directed therapy within 7 days of randomization
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 114
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 38
Disease Related:
• Primary tumor in situ
- Subjects must have their primary tumor resected to be eligible for this study
• Known history of central nervous system metastases. An MRI or CT scan of the brain or head will be performed within 28 days of randomization.
• History of arterial or venous thrombosis within 6 months prior to randomization
• History of bleeding diathesis or clinically significant bleeding within 14 days of randomization
• Previous treatment (excluding surgery and palliative radiotherapy) for advanced or metastatic renal cell carcinoma
• Focal radiation therapy for palliation of pain from bony metastases within 14 days of randomization.
• Subjects who received radiation therapy must have recovered from all radiation induced toxicities prior to randomization
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 (vatalinib), AZD 2171, AEE-788
• Currently or previously treated with bevacizumab
• Currently or previously treated with AMG 386, or other molecules that inhibit the angiopoietins or Tie2 receptor including but not limited to, AZD-5180, XL-820, CEP 11981/SSR-106462, BSF-466,895, CGI-1842, LOC-590, XL-184, or CP-8681596
• Concomitant or use within 30 days prior to randomization of any strong inducer of CYP3A4 including, but not limited to, rifampin, St. John’s wort, phenytoin, carbamazepine, phenobarbital and dexamethasone
General Medical:
• Known ongoing pancreatitis
• Myocardial infarction, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure, grade 2 or greater peripheral vascular disease, arrhythmias not controlled by outpatient medication, or unstable angina within 1 year prior to randomization
• Major surgery within 4 weeks before randomization or still recovering from prior surgery
• History of allergic reactions to bacterially produced proteins
• Pregnant (i.e., positive beta-human chorionic gonadotropin test) or is breast feeding
• Exclude subjects with a history of prior malignancy, except:
o 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
o Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease
o Adequately treated cervical carcinoma in situ without evidence of disease
o Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Minor surgical procedures, placement of access device, or fine needle
aspiration within 7 days of first dose
• Uncontrolled hypertension as defined as diastolic > 90 mmHg OR systolic >150 mmHg. Anti-hypertensive medications are permitted.
• Known active or ongoing infection within 14 days before randomization
• Subject known to have tested positive for HIV
• Subject known to have chronic hepatitis
• Any condition which in the investigator’s opinion makes the subject unsuitable for study participation
• History of pulmonary hemorrhage or gross hemoptysis (1/2 teaspoon or more of bright red blood) within 6 months before randomization
• Concurrent or prior (within 1 week before randomization) anticoagulation therapy, excluding Aspirin. The concurrent use of low molecular weight heparin or low dose warfarin (ie, = 1 mg daily) for prophylaxis again
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