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Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer

Primary Purpose

Breast Carcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fingolimod
Fingolimod Hydrochloride
Questionnaire Administration
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Breast Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to complete questionnaires by themselves or with assistance.
  • Paclitaxel at a dose of 80 mg/m^2 given every week for a scheduled course of 12 weeks for treating breast cancer.
  • Life expectancy >= 6 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1.
  • Negative pregnancy test (serum or urine) done =< 14 days prior to registration, for persons of childbearing potential only.
  • Provide written informed consent.

Exclusion Criteria:

  • Previous exposure to paclitaxel (please note that it is acceptable for patients to receive non-neurotoxic chemotherapy, like doxorubicin hydrochloride (Adriamycin) and cyclophosphamide (AC), before or after the weekly paclitaxel and/or to receive concurrent anti-her 2 therapy).

  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:

    • Pregnant persons
    • Nursing persons
    • Persons of childbearing potential who are unwilling to employ adequate contraception.
  • Previous diagnosis of diabetic or other peripheral neuropathy.
  • Current or previous use of fingolimod.
  • History of the following preexisting conditions: ischemic heart disease, cardiac arrest, cerebrovascular disease, uncontrolled hypertension, symptomatic bradycardia, macular edema, recurrent syncope, severe untreated sleep apnea, herpes simplex virus (HSV), varicella zoster virus (VZV), chronic hepatitis, tuberculosis, fungal infections, skin cancer, or diabetes.
  • Myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization or class III/IV heart failure < 6 months prior to registration.
  • History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome, unless patient has a functioning pacemaker.
  • History of a hypersensitivity reaction to fingolimod or any of the excipients including rash, urticarial, and angioedema upon treatment initiation.
  • Baseline corrected QT (QTC) interval >= 450 ms (on electrocardiography [EKG]).
  • Concurrent use of a class Ia or III antiarrhythmic.
  • Drugs with a known risk of torsades de pointes.
  • Concurrent use of beta blockers, calcium channel blockers or digoxin.
  • Use of immunosuppressive, or immune-modulating therapies that may have immunosuppressive effects.
  • Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive.

  • Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Or psychiatric illness/social situations that would limit compliance with study requirements.
  • Receiving any other investigational agent.
  • Family history of a genetic/familial neuropathy.
  • Received a vaccine (inactivated) =< 14 days prior to registration.

Sites / Locations

  • Mayo Clinic
  • The Ohio State University
  • Virginia Commonwealth University/ Massey Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Prevention (fingolimod hydrochloride)

Arm Description

Patients receive fingolimod hydrochloride PO QD starting the day before chemotherapy, the day of chemotherapy, and 1 day after chemotherapy for 12 weeks.

Outcomes

Primary Outcome Measures

Serially measured total sensory neuropathy scores
Obtained from the 6 individual Quality of Life Questionnaire (QLQ)-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet). The hypothesis will be tested with the two-sided one sample t-test at a significance level of 10%. In the event that the distribution of the patient?s average total sensory neuropathy scores is not approximately normally distributed, then variable transformation or a nonparametric one-sample Wilcoxon signed-rank test will be considered as alternative approaches.

Secondary Outcome Measures

Incidence of adverse events (AEs)
Scored using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0. Will be summarized by reporting the number and percentage of patients. The maximum grade for each type of AE will be recorded for each patient and data listings and frequency tables will be clinically reviewed to determine overall patterns, including AE attribution (possible, probable, and definite) to fingolimod. Additionally, the number and percentage of patients experiencing sensory neuropathy as defined by NCI CTCAE v5.0 will be tabulated by grade (none, mild, moderate, and severe); the proportion of patients experiencing >= grade 2 (moderate) CTCAE sensory neuropathy will estimated with the exact 90% confidence interval.

Full Information

First Posted
May 6, 2019
Last Updated
July 20, 2023
Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03941743
Brief Title
Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer
Official Title
Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot Trial
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
December 12, 2019 (Actual)
Primary Completion Date
June 5, 2020 (Actual)
Study Completion Date
November 23, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This trial phase I studies how well fingolimod works in preventing chemotherapy-induced nerve pain (neuropathy) in patients with breast cancer who are taking paclitaxel. Fingolimod acts by suppressing immune reactions in the brain. This study is being done to see if fingolimod can reduce neuropathy caused by paclitaxel.
Detailed Description
PRIMARY OBJECTIVES: I. To obtain preliminary data to support whether fingolimod hydrochloride (fingolimod) will prevent chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving weekly adjuvant/neoadjuvant paclitaxel therapy. SECONDARY OBJECTIVES: I. To obtain pilot data regarding the possible relative toxicities related to fingolimod therapy in this study situation. OUTLINE: Patients receive fingolimod hydrochloride orally (PO) once daily (QD) starting the day before chemotherapy, the day of chemotherapy, and 1 day after chemotherapy for 12 weeks. After the completion of study, patients are followed up at 6, 12, and 18 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Carcinoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
2 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Prevention (fingolimod hydrochloride)
Arm Type
Experimental
Arm Description
Patients receive fingolimod hydrochloride PO QD starting the day before chemotherapy, the day of chemotherapy, and 1 day after chemotherapy for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Fingolimod
Intervention Description
Given PO
Intervention Type
Drug
Intervention Name(s)
Fingolimod Hydrochloride
Other Intervention Name(s)
FTY-720, FTY720, Gilenya
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Serially measured total sensory neuropathy scores
Description
Obtained from the 6 individual Quality of Life Questionnaire (QLQ)-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 questions that quantify numbness, tingling, and pain in the fingers (or hands) and toes (or feet). The hypothesis will be tested with the two-sided one sample t-test at a significance level of 10%. In the event that the distribution of the patient?s average total sensory neuropathy scores is not approximately normally distributed, then variable transformation or a nonparametric one-sample Wilcoxon signed-rank test will be considered as alternative approaches.
Time Frame
Baseline up to 18 months
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Description
Scored using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version (v) 5.0. Will be summarized by reporting the number and percentage of patients. The maximum grade for each type of AE will be recorded for each patient and data listings and frequency tables will be clinically reviewed to determine overall patterns, including AE attribution (possible, probable, and definite) to fingolimod. Additionally, the number and percentage of patients experiencing sensory neuropathy as defined by NCI CTCAE v5.0 will be tabulated by grade (none, mild, moderate, and severe); the proportion of patients experiencing >= grade 2 (moderate) CTCAE sensory neuropathy will estimated with the exact 90% confidence interval.
Time Frame
Up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to complete questionnaires by themselves or with assistance. Paclitaxel at a dose of 80 mg/m^2 given every week for a scheduled course of 12 weeks for treating breast cancer. Life expectancy >= 6 months. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1. Negative pregnancy test (serum or urine) done =< 14 days prior to registration, for persons of childbearing potential only. Provide written informed consent. Exclusion Criteria: Previous exposure to paclitaxel (please note that it is acceptable for patients to receive non-neurotoxic chemotherapy, like doxorubicin hydrochloride (Adriamycin) and cyclophosphamide (AC), before or after the weekly paclitaxel and/or to receive concurrent anti-her 2 therapy). Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: Pregnant persons Nursing persons Persons of childbearing potential who are unwilling to employ adequate contraception. Previous diagnosis of diabetic or other peripheral neuropathy. Current or previous use of fingolimod. History of the following preexisting conditions: ischemic heart disease, cardiac arrest, cerebrovascular disease, uncontrolled hypertension, symptomatic bradycardia, macular edema, recurrent syncope, severe untreated sleep apnea, herpes simplex virus (HSV), varicella zoster virus (VZV), chronic hepatitis, tuberculosis, fungal infections, skin cancer, or diabetes. Myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization or class III/IV heart failure < 6 months prior to registration. History or presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block or sick sinus syndrome, unless patient has a functioning pacemaker. History of a hypersensitivity reaction to fingolimod or any of the excipients including rash, urticarial, and angioedema upon treatment initiation. Baseline corrected QT (QTC) interval >= 450 ms (on electrocardiography [EKG]). Concurrent use of a class Ia or III antiarrhythmic. Drugs with a known risk of torsades de pointes. Concurrent use of beta blockers, calcium channel blockers or digoxin. Use of immunosuppressive, or immune-modulating therapies that may have immunosuppressive effects. Immunocompromised patients including patients known to be human immunodeficiency virus (HIV) positive. Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection Unstable angina pectoris Cardiac arrhythmia Or psychiatric illness/social situations that would limit compliance with study requirements. Receiving any other investigational agent. Family history of a genetic/familial neuropathy. Received a vaccine (inactivated) =< 14 days prior to registration.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles L Loprinzi
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43212
Country
United States
Facility Name
Virginia Commonwealth University/ Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mayo.edu/research/clinical-trials.
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer

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