Ispinesib in Treating Patients With Metastatic or Unresectable Kidney Cancer

Inclusion Criteria:

• Patients must have histologically or cytologically confirmed renal cell carcinoma which is metastatic (M1); histopathology is not restricted; patients with unresectable primary tumor (but MO) are also eligible
• Patients must have measurable disease; x-rays, scans or physical examinations used for tumor measurement must have been completed within 28 days prior to registration; x-rays, scans or physical examinations for non-measurable disease must have been completed within 42 days prior to registration
• Patients with metastatic disease who have a resectable primary tumor and are deemed a surgical candidate may have undergone resection and have recovered from surgery; at least 28 days must have elapsed since surgery and patient must have recovered from any adverse effects of surgery
• Patients must have discontinued therapy due to toxicity or demonstrated progression of disease following a minimum of one prior therapy; prior therapies may include: immunotherapy with either interferon (IFN) and/or Interleukin-2 (IL-2) or prior anti-angiogenesis agents; at least 28 days must have elapsed since the last treatment; patients must have recovered from any adverse effects of prior therapy
• Patients may have received prior radiation therapy; at least 21 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
• Patients may not have received prior tubule, DNA, or mitosis targeting agents for the treatment of renal cell carcinoma
• Patients must have a ECOG performance status of 0 - 2
• Pregnant or nursing women may not participate in this trial; women and men of reproductive potential must have agreed to use an effective contraceptive method; women of child-bearing potential must have a negative urine pregnancy test
• Patients with a history of brain metastases or who currently have treated or untreated brain metastases are not eligible; patients with clinical evidence of brain metastases must have a brain CT or MRI negative for metastatic disease within 56 days prior to registration
• Absolute granulocyte count (AGC) ≥ 1,500 cells/mm3, hemoglobin ≥ 9 mg/dl, and a platelet count ≥ 100,000 cells/mm3 within 14 days prior to registration
• Patients must have a total bilirubin < 2 mg/dl obtained within 14 days prior to registration
• Patients must have SGOT and SGPT =< 2.5 x institutional upper limit of normal within 14 days prior to registration
• Patients must have a serum creatinine =< 2.0 or a calculated creatinine clearance >= 40 mL/min for patients with creatinine levels above institutional normal; this must be obtained within 14 days prior to registration
• Patients must have a corrected QT interval less than 0.47 seconds
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

• Prohibited medications; SB-715992 is a moderate to significant in vitro inhibitor of CYP3A4; the following lists of medications/substances are moderate to significant inhibitors/inducers of CYP3A4 that, if administered concomitantly with SB-715992, may alter study drug exposure; the use of these medications/ substances within 14 days (=< 6 months for amiodarone) prior to the administration of the first dose of SB-715992 through discontinuation from the study is prohibited

  • Inhibitors of CYP3A4:

    • Antibiotics: Clarithromycin, erythromycin, troleandomycin, rifabutin, rifapentine
    • Antifungals: itraconazole, ketoconazole, fluconazole (doses > 200 mg/day), voriconazole
    • Antidepressants: nefazodone, fluovoxamine
    • Calcium channel blockers: verapamil, diltiazem
    • Miscellaneous: amiodarone*, bitter orange
  • Use of amiodarone within 6 months prior to the administration of the first dose of SB-715992 is prohibited.

  • Inducers of CYP3A4:

    • Anticonvulsants: phenytoin, carbamazepine, phenobarbital, oxcarbazepine
    • Antibiotics: rifampin, rifabutin, rifapentine
    • Miscellaneous: St. John's Wort, modafinil
• Patients must not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to SB-715992
• Patients must not have any uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements
• Patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy; therefore, HIV-positive patients receiving combination anti-retroviral therapy are not eligible because of possible pharmacokinetic interactions with SB-715992
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years