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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-12-11

Study Completion Date

2024-12-18

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Paclitaxel Plus Monoclonal Antibody Therapy in Treating Women With Recurrent or Metastatic Breast Cancer

NCT00003539

Breast Cancer

COMPLETED PHASE2

Neoadjuvant Neratinib in Stage I-III HER2-Mutated Lobular Breast Cancers

NCT05919108

Anatomic Stage I Breast Cancer Anatomic Stage II Breast Cancer Anatomic Stage III Breast Cancer +1 more

RECRUITING PHASE2

Paclitaxel With or Without Gemcitabine in Treating Women With Advanced Breast Cancer

NCT00006459

Breast Cancer

COMPLETED PHASE3

Suramin and Paclitaxel in Treating Women With Stage IIIB-IV Breast Cancer

NCT00054028

Recurrent Breast Cancer Stage IIIB Breast Cancer Stage IV Breast Cancer

COMPLETED PHASE1/PHASE2

A Study of Biweekly Gemcitabine, Paclitaxel, and Avastin in Patients With Metastatic Breast Cancer

NCT00618826

Metastatic Breast Cancer

COMPLETED PHASE2

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of nilotinib hydrochloride monohydrate (nilotinib) in combination with paclitaxel.

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.

SECONDARY OBJECTIVES:

I. To determine the effect of paclitaxel on pharmacokinetics (PK) of nilotinib in the study population.

II. To determine the effect of nilotinib on PK of paclitaxel in the study population.

OUTLINE: This is a phase Ib, dose-escalation study of nilotinib hydrochloride monohydrate.

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

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Anatomic Stage I Breast Cancer AJCC v8 Anatomic Stage IA Breast Cancer AJCC v8 Anatomic Stage IB Breast Cancer AJCC v8 Anatomic Stage II Breast Cancer AJCC v8 Anatomic Stage IIA Breast Cancer AJCC v8 Anatomic Stage IIB Breast Cancer AJCC v8 Anatomic Stage III Breast Cancer AJCC v8 Anatomic Stage IIIA Breast Cancer AJCC v8 Anatomic Stage IIIB Breast Cancer AJCC v8 Anatomic Stage IIIC Breast Cancer AJCC v8 Prognostic Stage I Breast Cancer AJCC v8 Prognostic Stage IA Breast Cancer AJCC v8 Prognostic Stage IB Breast Cancer AJCC v8 Prognostic Stage II Breast Cancer AJCC v8 Prognostic Stage IIA Breast Cancer AJCC v8 Prognostic Stage IIB Breast Cancer AJCC v8 Prognostic Stage III Breast Cancer AJCC v8 Prognostic Stage IIIA Breast Cancer AJCC v8 Prognostic Stage IIIB Breast Cancer AJCC v8 Prognostic Stage IIIC Breast Cancer AJCC v8

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dose level 1

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 Type EXPERIMENTAL

Nilotinib

Intervention Type DRUG

Given PO

Nilotinib Hydrochloride Monohydrate

Intervention Type DRUG

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.

Paclitaxel

Intervention Type DRUG

Given IV weekly on days 1, 8, 15, of every 21 days, at a starting dose of 80mg/m2

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Dose level 2

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 Type EXPERIMENTAL

Nilotinib

Intervention Type DRUG

Given PO

Nilotinib Hydrochloride Monohydrate

Intervention Type DRUG

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.

Paclitaxel

Intervention Type DRUG

Given IV weekly on days 1, 8, 15, of every 21 days, at a starting dose of 80mg/m2

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Dose level 3

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 Type EXPERIMENTAL

Nilotinib

Intervention Type DRUG

Given PO

Nilotinib Hydrochloride Monohydrate

Intervention Type DRUG

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.

Paclitaxel

Intervention Type DRUG

Given IV weekly on days 1, 8, 15, of every 21 days, at a starting dose of 80mg/m2

Questionnaire Administration

Intervention Type OTHER

Ancillary studies

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Nilotinib

Given PO

Intervention Type DRUG

Nilotinib Hydrochloride Monohydrate

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.

Intervention Type DRUG

Paclitaxel

Given IV weekly on days 1, 8, 15, of every 21 days, at a starting dose of 80mg/m2

Intervention Type DRUG

Questionnaire Administration

Ancillary studies

Intervention Type OTHER

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

AMN 107 Base Form AMN107 Nilotinib Monohydrochloride Monohydrate Tasigna Anzatax Asotax Bristaxol Praxel Taxol Taxol Konzentrat

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
* Demonstrate adequate electrolyte values as defined below. Hypokalemia and/or hypomagnesemia 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 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.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No