A Randomized, Double Blinded, Multi-Center Study 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Sorafenib in Combination with AMG 386 or Placebo in Subjects with Metastatic Clear Cell Carcinoma of the Kidney
- Conditions
- A Randomized, Double Blinded, Multi-Center Phase 2 Study to Estimate the Efficacy and Evaluate the Safety and Tolerability of Sorafenib in Combination with AMG 386 or Placebo in Subjects with Metastatic Clear Cell Carcinoma of the KidneyMedDRA version: 9.1Level: LLTClassification code 10050513Term: Metastatic renal cell carcinoma
- Registration Number
- EUCTR2007-000147-98-FR
- Lead Sponsor
- Amgen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 152
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 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 guidelines with modifications.
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:
- Creatinine = 2.0 x ULN
- 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
• Amylase = 1.5 x ULN
• Lipase = 1.5 x ULN
• 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:
- INR= 1.5
- Partial thromboplastin time (PTT) within normal limits
General:
• Able to tolerate infusions and self-administer oral medications
• Competent to comprehend, sign, and date an institutional review board (IRB) -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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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 will be performed within 21 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 AMG 706, bevacizumab or small molecule inhibitors of VEGF including, but not limited to, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AEE-788, BAY 43-9006 (sorafenib)
• 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:
• 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 30 days 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
• Prior malignancy (other than thyroid cancer, in situ cervical cancer, or nonmelanomatous cancer of the skin treated with curative intent and without evidence of disease for = 3 years before randomization)
• Central venous catheter placement (including tunneled catheters and port-o-caths) within 7 days of randomization
• 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 against central venous catheter thrombosis is acceptable
Other:
• Other investigational procedures are excluded
• Subject not consenting to the use of highly effective contraceptive, e.g. double barrier method (i.e. condom plus diaphragm) precautions during the course of the study and for 6 months after administration of the last study medication
• Subject currently is enrolled in or has not ye
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