Ixabepilone in Treating Patients With Metastatic, Recurrent, or Unresectable Kidney Cancer

Study Overview
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Brief Summary
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This phase II trial is studying how well ixabepilone works in treating patients with metastatic, recurrent, or unresectable kidney cancer. Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the objective response rate in patients with metastatic, recurrent, or unresectable renal cell carcinoma treated with ixabepilone. SECONDARY OBJECTIVES: I. Determine the progression-free and overall survival rates in patients treated with this drug. II. Determine the toxicity of this drug in these patients. III. Correlate VHL gene mutations with response in patients treated with this drug. IV. Correlate VHL pathway protein expression with response in patients treated with this drug. OUTLINE: This is a multicenter study. Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 9 weeks until disease progression and then every 3 months for up to 2 years.

Official Title
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A Phase II Trial of BMS 247550 (Ixabepilone) in Advanced Renal Cell Carcinoma

Conditions
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Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Drug: ixabepilone
* Other: laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed renal cell carcinoma of 1 of the following subtypes: Clear cell Papillary, type I or II Chromophobe Collecting duct Medullary Metastatic, recurrent, or unresectable disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan No known active brain metastases requiring steroid or anticonvulsant therapy Patients with definitively treated brain metastases are eligible provided they are not on steroids or anticonvulsants AND show no evidence of disease progression for ≥ 3 months after completion of definitive therapy Performance status - ECOG 0-2 At least 3 months WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST and ALT ≤ 2.5 times ULN Creatinine ≤ 1.5 times ULN Glomerular filtration rate ≥ 50 mL/min No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No ongoing or active infection No HIV positivity No peripheral neuropathy > grade 1 No psychiatric illness or social situation that would preclude study compliance No history of allergic reaction attributed to compounds of similar chemical or biological composition to study drug No history of severe hypersensitivity reaction to agents containing Cremophor® EL No other active malignancy Curatively treated malignancies are allowed provided the risk of recurrent disease at the time of study enrollment is < 20% No other uncontrolled illness More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered No prior tubule inhibitors, including, but not limited to, any of the following: Vinca alkaloids (e.g., vinblastine, vincristine, or vinorelbine) Taxanes (e.g., docetaxel or paclitaxel) Epothilones No other concurrent chemotherapy See Disease Characteristics No concurrent hormonal therapy except steroids for adrenal failure or hypersensitivity prophylaxis or hormones for non-disease related conditions (e.g., insulin for diabetes) More than 4 weeks since prior radiotherapy and recovered No concurrent palliative radiotherapy No other concurrent investigational agents No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive ixabepilone IV over 3 hours on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: ixabepilone<br>* Given IV<br>* Other names: Ixempra;Other: laboratory biomarker analysis<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (partial or complete) |  | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | PFS rate will be estimated using the Kaplan-Meier method. Median PFS time and its associated 90% confidence interval will be estimated using the method of Brookmeyer and Crowley. | From the start of treatment to time of progression, assessed up to 5 years | 
| Overall survival (OS) | OS rate will be estimated using the Kaplan-Meier method. Median OS time and its associated 90% confidence interval will be estimated using the method of Brookmeyer and Crowley. | Up to 5 years |