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

This is an interventional treatment trial for Anatomic Stage I Breast Cancer AJCC v8 Read More

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

  • Patients with ECOG scores of 3 or greater typically do not receive chemotherapeutic 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 with creatinine levels above institutional normal.
• Corrected QT interval (QTc) < 450 milliseconds.
• If a female subject is with child bearing potential, she must have a negative pregnancy test at screening.
• Female subjects of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation and for 3 months after completion of study treatment administration. Adequate contraception includes methods such as oral contraceptives, double barrier method (condom plus spermicide or diaphragm), or abstaining from sexual intercourse.
• Be willing and able to understand and sign the written informed consent document.

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 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
• 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.