A Phase II Study of Axitinib in Patients With Metastatic Renal Cell Cancer Unsuitable for Nephrectomy

Inclusion Criteria

• Histologically confirmed metastatic renal cell carcinoma of predominant clear cell histology
• Unsuitable for nephrectomy
• Unsuitable for 'watch and wait' policy
• No prior systemic therapy for renal cell carcinoma
• Measurable metastatic disease using RECIST v1.1
• Life expectancy 12 weeks or greater
• ECOG performance status 0 or 1
• Adequate organ function as defined by serum aspartate transaminase (AST) or serum alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or AST and ALT ≤5 x ULN if liver function abnormalities are due to liver metastases; total serum bilirubin ≤1.5 x ULN
• Adequate haematological function as defined by absolute neutrophil count (ANC) ≥1500/μL, platelets ≥75,000/μL, haemoglobin ≥9.0 g/dL and prothrombin time (PT) ≤1.5 x ULN
• Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min;
• Urinary protein 6 months. In the case of a solitary brain metastasis which has been resected, there must be evidence of a disease-free interval of at least 3 months post-surgery. All patients previously treated for brain metastases must be stable off corticosteroid therapy for at least 28 days.
• The presence of active second malignancy.
• Women who are pregnant or are breastfeeding. Female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy.
• Male patients must be surgically sterile or must agree to use effective contraception during the period of therapy.
• Current signs or symptoms of severe progressive or uncontrolled hepatic, endocrine, pulmonary disease other than directly related to RCC.
• Gastrointestinal abnormalities including:
• inability to take oral medication;
• requirement for intravenous alimentation;
• prior surgical procedures affecting absorption including total gastric resection;
• treatment for active peptic ulcer disease in the past 6 months;
• active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy;
• malabsorption syndromes.
• Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (see section 8.12, concomitant therapy).
• Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (see section 8.12, concomitant therapy).
• Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose anticoagulants for maintenance of patency of central venous access device or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
• Active seizure disorder, spinal cord compression, or carcinomatous meningitis.
• Any of the following within 12 months prior to study entry: myocardial infarction, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack.
• Deep vein thrombosis or pulmonary embolism within 6 months prior to study entry.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Known galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption