Nilotinib in Preventing Paclitaxel-Induced Peripheral Neuropathy in Patients With Stage I-III Breast Cancer

Inclusion Criteria

• Men or Women with a known diagnosis of breast cancer stages I-III.
• Be eligible for weekly or dose dense single agent paclitaxel therapy based on physician assessment.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status = = 2,000/uL.
• Absolute neutrophil count >= 1,500/uL.
• Platelets >= 100,000/uL.
• Total bilirubin = = 50 mL/min for patients with creatinine levels above institutional normal.
• Corrected QT interval (QTc) grade 1 neuropathy during previous therapies for early stage breast cancer.
• Has experienced prior treatment-related toxicities that have not recovered to grade 1 or less (except for alopecia).
• Has a history of grade 3-4 immediate hypersensitivity reaction to paclitaxel.
• Has a history of clinically significant allergic reactions attributed to compounds of similar chemical or biologic composition to nilotinib or paclitaxel.
• Has 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.
• Is currently pregnant or breast feeding as there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nilotinib and paclitaxel.
• Has any other medical or psychiatric condition that in the opinion of the investigator would make the study therapy unsafe for the patient.
• Has gastrointestinal (GI) disorders or impairment of GI function that is likely to significantly alter the absorption of nilotinib
• Has a marked baseline abnormal heart rhythm such as prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc of > 450msec)
• Has a history of additional risk factors for TdP (e.g., heart failure, hypokalemia, hypomagnesemia, family history of Long QT Syndrome)
• Uses potent CYP3A4 inhibitors (grapefruit juice, cyclosporine, ketoconazole, ritonavir) and if treatment cannot be either safely discontinued or switched to a different medication prior to starting nilotinib.
• Has a known diagnosis of human immunodeficiency virus (HIV) and is currently taking combination antiretroviral therapy known or suspected to affect paclitaxel pharmacokinetics (PK).
• Is concurrently using potent OATP1B1 inhibitors, including antibiotics (rifampicin, rifamycin SV, systemic fusidic acid, clarithromycin, erythromycin, roxithromycin, telithromycin), antiretrovirals (indinavir, saquinavir, ritonavir), cyclosporine, and gemfibrozil.