AZD2171 in Treating Patients With Refractory Metastatic Kidney Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed clear cell renal cell cancer

  • Must be predominantly metastatic disease
  • Refractory disease
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mmby conventional techniques or ≥ 10 mm by spiral CT scan
• No known brain metastases
• ECOG performance status 0-2
• Karnofsky 60-100%
• WBC ≥ 3,000/mm^3
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 8.0 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Bilirubin normal
• Creatinine normal OR creatinine clearance > 60 mL/min
• Blood pressure < 140/90 mm Hg on 2 separate occasions not more than 6 weeks prior to enrollment and not less than 24 hours apart (stable antihypertensive regimen allowed)
• Mean QTc ≤ 470 msec (with Bazett's correction)
• Less than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of familial long QT syndrome
• No cardiac arrhythmia
• No unstable angina pectoris
• No symptomatic congestive heart failure
• No New York Heart Association class III or IV disease
• No ongoing or active infection
• No hypertension
• No other uncontrolled intercurrent illness
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AZD2171
• No psychiatric illness or social situations that would limit compliance with study requirements
• See Disease Characteristics
• More than 4 weeks since prior radiotherapy and recovered
• More than 4 weeks since prior major surgery and recovered
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• More than 30 days since other prior investigational agents
• No prior therapy with vascular endothelial growth factor (VEGF) binding agents or VEGF receptor (VEGFR) tyrosine kinase inhibitors
• No more than 1 prior nonVEGF-directed systemic therapy for this disease
• No concurrent medication that may markedly affect renal function (e.g., vancomycin, amphotericin, ibuprofen, pentamidine)
• No combination antiretroviral therapy for HIV-positive patients
• No concurrent hematopoietic growth factors except epoetin alfa and bisphosphonates
• No concurrent hormones or other chemotherapeutic agents except for steroids given for adrenal failure and hormones administered for nondisease-related conditions (e.g. insulin for diabetes)
• No concurrent palliative or therapeutic radiation therapy
• No concurrent drugs or biologics with proarrhythmic potential
• No other concurrent investigational or commercial agents or therapies to treat the patient's malignancy