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 onphysician assessment.

• Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Patients with ECOG scores of 3 or greater typically do not receivechemotherapeutic intervention.

• Leukocytes >= 2,000/uL.

• Absolute neutrophil count >= 1,500/uL.

• Platelets >= 100,000/uL.

• Total bilirubin =< upper limit of normal (ULN).

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal.

• Creatinine within normal institutional limits OR >= 50 mL/min for patients withcreatinine levels above institutional normal.

• Corrected QT interval (QTc) < 450 milliseconds.

• If a female subject is with child bearing potential, she must have a negativepregnancy test at screening.

• Female subjects of child-bearing potential and men must agree to use adequatecontraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment administration. Adequate contraceptionincludes methods such as oral contraceptives, double barrier method (condom plusspermicide or diaphragm), or abstaining from sexual intercourse.

• Be willing and able to understand and sign the written informed consent document.

• Demonstrate adequate electrolyte values as defined below. Hypokalemia and/orhypomagnesemia must be corrected prior to initiating nilotinib:

• Calcium 8.6-10.5mg/dL

• Magnesium 1.6-2.6mg/dL

Exclusion Criteria:

• Known distant metastatic disease.

• Is HER2+ and is receiving paclitaxel in conjunction with trastuzumab +/- pertuzumab.

• Has experienced > grade 1 neuropathy during previous therapies for early stagebreast 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 compoundsof similar chemical or biologic composition to nilotinib or paclitaxel.

• Has uncontrolled intercurrent illness including, but not limited to, ongoing oractive infection, symptomatic congestive heart failure, unstable angina pectoris,cardiac arrhythmia, or psychiatric illness/social situations that would limitcompliance with study requirements.

• Is currently pregnant or breast feeding as there is an unknown but potential riskfor adverse events in nursing infants secondary to treatment of the mother withnilotinib and paclitaxel.

• Has any other medical or psychiatric condition that in the opinion of theinvestigator would make the study therapy unsafe for the patient.

• Has gastrointestinal (GI) disorders or impairment of GI function that is likely tosignificantly 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 adifferent medication prior to starting nilotinib.

• Has a known diagnosis of human immunodeficiency virus (HIV) and is currently takingcombination antiretroviral therapy known or suspected to affect paclitaxelpharmacokinetics (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.