AZD2171 in Treating Patients With Progressive Locally Recurrent or Metastatic Kidney Cancer That Cannot Be Removed By Surgery

• Objective response rate and rate of stable disease ≥ 4 months [ Designated as safety issue: No ]
• Duration of response or stable disease [ Designated as safety issue: No ]
• Progression-free, median, and overall survival [ Designated as safety issue: No ]
• Safety and tolerability [ Designated as safety issue: Yes ]
• Correlation of levels of soluble markers of angiogenic growth factors and receptors and circulating endothelial cells with clinical outcome [ Designated as safety issue: No ]
• Correlation of changes in blood flow and vessel permeability with clinical outcome [ Designated as safety issue: No ]

RATIONALE: AZD2171 may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying AZD2171 to see how well it works in treating patients with progressive locally recurrent or metastatic kidney cancer that cannot be removed by surgery.

OBJECTIVES:

• Determine the clinical benefit rate (objective response rate and rate of stable disease for ≥ 4 months) in patients with progressive unresectable, locally recurrent or metastatic renal cell carcinoma treated with AZD2171.
• Determine the duration of response or stable disease in patients treated with this drug.
• Determine progression-free, median, and overall survival of patients treated with this drug.
• Determine the safety and tolerability of this drug in these patients.
• Correlate levels of soluble markers of angiogenic growth factors and receptors and circulating endothelial cells with clinical outcome in patients treated with this drug.
• Correlate changes in blood flow and vessel permeability with clinical outcome in patients treated with this drug.

OUTLINE: This is a multicenter study.

Patients receive oral AZD2171 once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 12-37 patients will be accrued for this study within 4-12 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell cancer

  • Locally recurrent or metastatic disease
  • Progressive unresectable disease
  • Not considered curable by standard therapy

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan

  • Bone lesions are not considered measurable disease
  • Sole site of measurable disease may lie within a previously irradiated field provided there has been subsequent documented disease progression
• No known brain metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2 OR
• Karnofsky 60-100%

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 3 times ULN

Renal

• Creatinine ≤ 1.5 times ULN OR
• Creatinine clearance ≥ 60 mL/min
• No proteinuria > +1 on 2 consecutive dipstick tests taken ≥ 1 week apart

Cardiovascular

• QTc ≤ 470 msec (with Bazett's correction) by ECG
• No history of familial long QT syndrome
• No hypertension
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

• No New York Heart Association class III or IV disease

  • Class II disease with increased monitoring is allowed

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drug
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior immunotherapy or gene therapy
• No drugs or biologics with proarrythmic potential

Chemotherapy

• No prior systemic chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy, except low-dose, non-myelosuppressive radiotherapy, and recovered
• No concurrent radiotherapy to the sole site of measurable disease

Surgery

• At least 4 weeks since prior major surgery and recovered

Other

• No prior investigational therapy
• No prior participation in another investigational study
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent anticancer therapy