Ixabepilone in Treating Patients With Metastatic or Recurrent Squamous Cell Cancer of the Head and Neck

PRIMARY OBJECTIVES:

I. To determine the response rate and toxicity of BMS-247550 given in two dosing schedules in taxane-naïve and taxane-exposed patients.

II. To provide information about the response rate and toxicity of BMS-247550 given in two dosing schedules.

SECONDARY OBJECTIVES:

I. To measure surviving expression and correlate with the therapeutic responsiveness to BMS-247550.

II. To determine the changes in tumor vascular density and endothelial cell apoptosis in response to therapy and the correlation of these changes to outcome.

OUTLINE: This is a randomized study. Patients are stratified according to prior taxane therapy (yes vs no) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms.

Arm I: 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.

Arm II: Patients receive ixabepilone IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

In both arms, patients achieving complete response (CR) receive 2 additional courses past CR if a minimum of 6 courses have been administered.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

Inclusion criteria

• Patients must have measurable histologically confirmed squamous cell carcinoma of the head and neck, excluding nasopharyngeal primaries, that is incurable with surgery or radiation therapy; disease must be measurable as defined by RECIST =< 4 weeks of randomization

• Patients must have distant metastases or locoregional recurrence or persistent disease within a radiation portal
• Baseline tumor measurements/evaluations must be obtained < 4 weeks prior to randomization
• Patients may have received up to one prior biotherapy regimen and treatment must have been completed at least 4 weeks prior to randomization; no more than two prior chemotherapy regimens for recurrent and/or metastatic disease are permitted; patients may have received prior docetaxel or paclitaxel, but must not have been previously treated with an investigational taxane; chemotherapy treatment must have been completed at least 4 weeks prior to randomization
• If the only site of measurable disease is a previously irradiated area, the patient must have documented progressive disease or biopsy-proven residual carcinoma; persistent disease after radiotherapy must be biopsy-proven at least 8 weeks after the completion of radiotherapy; patients must have completed radiotherapy at least 4 weeks prior to randomization
• Patients must not have a concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix; patients with prior malignancies who have been disease-free > 2 years are eligible
• Patients must have ECOG performance status of 0 or 1
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000/mm^3
• Serum creatinine =< 1.2 mg OR creatinine clearance >= 50 ml/min NOTE: Either calculated or actual creatinine clearance can be used NOTE: The creatinine clearance may be calculated by the Cockcroft-Gault formula
• Total bilirubin =< 1.5 mg
• (SGOT) AST, (SGPT) ALT =< 2 x institutional upper limit of normal
• Alkaline phosphatase =< 2 x institutional upper limit of normal
• Serum calcium within institutional normal range and no history of malignancy associated hypercalcemia
• Patients must not have a pre-existing peripheral neuropathy >= grade 2
• Patients must not have an active infection nor currently be receiving treatment for a recent infection
• Patients must have recovered from the effects of any recent surgery
• Female patients must not be pregnant or breastfeeding; the effects of BMS-247550 on pregnant women and on fetuses are unknown; however, the known toxicities, which include neutropenia, are likely to place pregnant women at increased risk; the mechanism of action of this compound, stabilization of microtubules in dividing cells, is highly likely to be teratogenic; taxanes, which have a similar mechanism of action, are known to be teratogenic NOTE: A negative serum pregnancy test is required =< 2 weeks of randomization for women of childbearing potential
• Women of childbearing potential and sexually active males must agree to use an accepted and effective method of contraception
• Patients must not have a known hypersensitivity to castor oil, or agents containing Cremophor El, or paclitaxel; patients with a history of grade 1 or uncomplicated, non-recurrent grade 2 hypersensitivity reactions associated with Cremophor will be eligible with prophylaxis