Nilotinib in Preventing Paclitaxel-Induced Peripheral Neuropathy in Patients With Stage I-III Breast Cancer
A Phase Ib Study of the Safety and Pharmacology of Nilotinib to Prevent Paclitaxel-Induced Peripheral Neuropathy in Patients With Breast Cancer
3 other identifiers
interventional
11
1 country
1
Brief Summary
This phase Ib trial studies the side effects and best dose of nilotinib in preventing paclitaxel-induced peripheral neuropathy in stage I-III breast cancer patients who are receiving paclitaxel therapy. Chemotherapy is the usual or standard treatment for breast cancer. It kills cancer cells and lowers the chance that the cancer will come back. Sometimes, this treatment can cause numbness and tingling, especially in the hands and feet. This is called chemotherapy-induced peripheral neuropathy. This study aims to test the safety and effectiveness, both good and bad, of taking nilotinib in preventing chemotherapy-induced peripheral neuropathy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Dec 2020
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 18, 2019
CompletedFirst Posted
Study publicly available on registry
December 20, 2019
CompletedStudy Start
First participant enrolled
December 11, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 19, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
December 18, 2024
CompletedResults Posted
Study results publicly available
June 29, 2025
CompletedJune 29, 2025
June 1, 2025
3.5 years
June 18, 2019
June 16, 2025
June 16, 2025
Conditions
Outcome Measures
Primary Outcomes (2)
Number of Adverse Events (Phase Ib)
Will be classified and attributed using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v)5.0 and will be summarized within and across dose levels using descriptive statistics. The overall number and percentage of patients experiencing adverse events (AEs) and toxicities will be summarized and reported as across all event types, non-hematologic AEs, hematologic AEs, and for each type. Specific focus will be in summarizing any neuropathy-related AEs by dose level and how this corresponds to our measures of OATP1B1 inhibition. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.
Up to 6 weeks
Recommended Phase II Dose (RP2D) of Nilotinib in Combination With Paclitaxel (Phase Ib)
The RP2D will be derived from an adaptive Bayesian method for dose-finding based on trade-offs between the probabilities of treatment efficacy and toxicity. In this design, treatment efficacy is defined as significant inhibition of OATP1B1 activity by nilotinib, without causing changes in the pharmacokinetic profiles of paclitaxel. Efficacy in this setting will be OATP1B1 inhibition as defined by a \>= 5-fold increase in the area under the curve (AUC) of GCDCA-S from pre- to post-treatment and/or detectable CDCA-24G levels post-treatment.
Up to 6 weeks
Other Outcomes (1)
Evaluate Effects of Nilotinib and Paclitaxel (Phase Ib) on Patients Through Pharmacokinetics (PK) for Clinical Significant Interactions.
: Pre-dose, prior to starting paclitaxel (day 1, day 8), prior to starting nilotinib (day 8 only), immediately prior to end of paclitaxel, after paclitaxel on days 1 and 8 and pre-dose, after nilotinib on day 7.
Study Arms (3)
Dose level 1
EXPERIMENTALPatients 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.
Dose level 2
EXPERIMENTALPatients 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.
Dose level 3
EXPERIMENTALPatients 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.
Interventions
Given PO on cycle 1 Days 7, 14, 15 once a day 24 hours prior to the paclitaxel infusion and again 30 minutes prior to the paclitaxel infusion on days 8, 15.
Given IV weekly on days 1, 8, 15, of every 21 days, at a starting dose of 80mg/m2
Eligibility Criteria
You may qualify if:
- 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.
- Demonstrate adequate electrolyte values as defined below. Hypokalemia and/or hypomagnesemia must be corrected prior to initiating nilotinib:
- +2 more criteria
You may not qualify if:
- 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
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Publications (1)
Stage TB, Hu S, Sparreboom A, Kroetz DL. Role for Drug Transporters in Chemotherapy-Induced Peripheral Neuropathy. Clin Transl Sci. 2021 Mar;14(2):460-467. doi: 10.1111/cts.12915. Epub 2020 Nov 9.
PMID: 33142018DERIVED
Related Links
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Nicole Williams
- Organization
- The Ohio State University Comprehensive Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Nicole Williams, MD
Ohio State University Comprehensive Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
June 18, 2019
First Posted
December 20, 2019
Study Start
December 11, 2020
Primary Completion
June 19, 2024
Study Completion
December 18, 2024
Last Updated
June 29, 2025
Results First Posted
June 29, 2025
Record last verified: 2025-06
Data Sharing
- IPD Sharing
- Will not share