• Activity [ Designated as safety issue: No ]
  
• Plasma pharmacokinetics and pharmacodynamics [ Designated as safety issue: No ]
  
• Nerve growth factor (NGF) levels [ Designated as safety issue: No ]
  
• Correlation of NGF levels with neurotoxicity [ Designated as safety issue: Yes ]
  
• Differences between responding and non-responding tumors as assessed by cDNA microarray [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the activity of ixabepilone in patients with renal cell carcinoma.
• Determine the plasma pharmacokinetics and pharmacodynamics of this drug using an assay that measures the relative amounts of polymerized versus unpolymerized endogenous tubulin in peripheral blood mononuclear cells of these patients.
• Determine the nerve growth factor (NGF) levels in patients before and after receiving this drug.
• Determine the correlation (if any) between NGF levels in these patients and neurotoxicity of this drug.
• If this drug is found to be active in more than 20% of these patients, determine whether differences exist between responding and non-responding tumors by analyzing tumor samples using cDNA microarray.

Secondary

• Determine the extent to which pharmacodynamic changes are observed over a range of doses of ixabepilone.
• Determine if cross-resistance to ixabepilone exists in patients who have received prior sorafenib or sunitinib.

OUTLINE: Patients are stratified according to histologic subtype (clear cell vs type I or II papillary vs chromophobe, collecting duct, or medullary).

Patients receive ixabepilone IV over 1 hour on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 36-114 patients (12-74 per stratum) will be accrued for this study within 7-48 months.

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed renal cell carcinoma

  • Eligible subtypes:

    • Clear cell
    • Type I or II papillary
    • Chromophobe
    • Collecting duct
    • Medullary
• Received prior, ineligible for, or refused interleukin-2
• Measurable disease
• No prior CNS metastases unless control was achieved with radiotherapy or surgical resection at least 6 months before study entry

• Must meet 1 of the following criteria:

  • Received sorafenib and/or sunitinib and had progressive disease while receiving the drugs
  • Evaluated for therapy with sorafenib and/or sunitinib and deemed to be ineligible
  • Evaluated for therapy with sorafenib and/or sunitinib and refused treatment

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 3 months

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Absolute granulocyte count at least 1,500/mm^3

Hepatic:

• Bilirubin no greater than 1.5 times normal (3 times normal if clinical evidence of Gilbert's disease)
• SGPT and SGOT no greater than 2.5 times normal

Renal:

• Creatinine no greater than 1.6 mg/dL OR
• Creatinine clearance at least 40 mL/min

Other:

• HIV negative
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 2 months after study completion
• No other serious concurrent medical illness
• No active, uncontrolled infection
• No other nonmalignant systemic disease that would preclude study participation
• No grade 2 or greater motor or sensory neuropathy
• No prior hypersensitivity reactions to agents containing Cremophor EL

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• At least 4 weeks since prior immunotherapy
• Prior thalidomide allowed

Chemotherapy:

• At least 4 weeks since prior cytotoxic chemotherapy
• No other prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior craniospinal or total body irradiation
• At least 4 weeks since other prior radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent investigational drugs
• No concurrent Hypericum perforatum (St. John's Wort)
• At least 2 weeks since prior targeted-therapy (cytostatic agents) and recovered