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

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PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) of nilotinib hydrochloride monohydrate (nilotinib) in combination with paclitaxel. (Phase Ib) II. To determine the toxicity profile (based on Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0) of nilotinib ...

PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) of nilotinib hydrochloride monohydrate (nilotinib) in combination with paclitaxel. (Phase Ib) II. To determine the toxicity profile (based on Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0) of nilotinib in combination with paclitaxel. (Phase Ib) III. To assess the efficacy of nilotinib versus (vs.) placebo in preventing paclitaxel-induced neuropathy when administered in combination with paclitaxel, as measured by patient reported outcomes using Chemotherapy-Induced Peripheral Neuropathy (CIPN)-20 and Brief Pain Inventory (BPI)-20. (Phase II) SECONDARY OBJECTIVES: I. To determine the effect of paclitaxel on pharmacokinetics (PK) of nilotinib in the study population. (Phase Ib) II. To determine the effect of nilotinib on PK of paclitaxel in the study population. (Phase Ib) III. To evaluate the effect of paclitaxel on PK of nilotinib in the study population. (Phase II) OUTLINE: This is a phase Ib, dose-escalation study of nilotinib hydrochloride monohydrate followed by phase a II study. PHASE Ib: Paclitaxel will be given weekly on days 1, 8, 15, of every 21 days, at a starting dose of 80mg/m2. Nilotinib will be given orally on cycle 1 Days 7, 14 once a day 24 hours prior to the paclitaxel infusion and again 30 minutes prior to the paclitaxel infusion on days 8, 15. During the cycle 1, PK will be obtained at baseline, during, and up to 24 hours after paclitaxel or nilotinib administration on the days 1, 7, 8. Patients will continue paclitaxel without nilotinib after cycle 1 as part of standard of care at the discretion of the treating investigator PHASE II: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive paclitaxel IV on days 1, 8, and 15. Patients also receive nilotinib hydrochloride monohydrate PO on days 7, 8, 14, and 15 of cycle 1 and days -1, 1, 7, 8, 14, and 15 of cycle 2. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. GROUP II: Patients receive paclitaxel IV on days 1, 8, and 15. In cycle 1. Patients also receive placebo PO on days 7, 8, 14, and 15 of cycle 1 and days -1, 1, 7, 8, 14, and 15 of cycle 2. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 3 and 6 months.

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