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出境医 / 临床实验 / Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer

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

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.

Condition or disease Intervention/treatment Phase
Breast Carcinoma Drug: Fingolimod Drug: Fingolimod Hydrochloride Other: Questionnaire Administration Phase 1

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.

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot Trial
Actual Study Start Date : May 24, 2019
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : June 1, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Prevention (fingolimod hydrochloride)
Patients receive fingolimod hydrochloride PO QD starting the day before chemotherapy, the day of chemotherapy, and 1 day after chemotherapy for 12 weeks.
 Drug: Fingolimod
Given PO

Drug: Fingolimod Hydrochloride
Given PO
Other Names:
  • FTY-720
  • FTY720
  • Gilenya

Other: Questionnaire Administration
Ancillary studies
Outcome Measures
Primary Outcome Measures :
  1. Serially measured total sensory neuropathy scores [ Time Frame: Baseline up to 18 months ]
    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 :
  1. Incidence of adverse events (AEs) [ Time Frame: Up to 18 months ]
    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.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations

Locations
Layout table for location information
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Charles L. Loprinzi    507-284-2511    mayocliniccancerstudies@mayo.edu   
Principal Investigator: Charles L. Loprinzi         
United States, Ohio
The Ohio State University Recruiting
Columbus, Ohio, United States, 43212
Contact: Erin Frey    614-293-6669    Erin.Frey@osumc.edu   
Principal Investigator: Maryam Lustberg, MD, MPH         
United States, Virginia
Virginia Commonwealth University/ Massey Cancer Center Recruiting
Richmond, Virginia, United States, 23298
Contact: Gwendolyn Parker, FNP-C    804-828-5090    Masseycpc@vcu.edu   
Principal Investigator: Zhi-Jian Chen, MD         
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Charles L Loprinzi Mayo Clinic
Tracking Information
First Submitted Date  ICMJE May 6, 2019
First Posted Date  ICMJE May 8, 2019
Last Update Posted Date November 13, 2020
Actual Study Start Date  ICMJE May 24, 2019
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 6, 2019) 		Serially measured total sensory neuropathy scores [ Time Frame: Baseline up to 18 months ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 6, 2019) 		Incidence of adverse events (AEs) [ Time Frame: Up to 18 months ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer
Official Title  ICMJE Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot Trial
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Breast Carcinoma
Intervention  ICMJE
  • Drug: Fingolimod
    Given PO
  • Drug: Fingolimod Hydrochloride
    Given PO
    Other Names:
    • FTY-720
    • FTY720
    • Gilenya
  • Other: Questionnaire Administration
    Ancillary studies
Study Arms  ICMJE Experimental: Prevention (fingolimod hydrochloride)
Patients receive fingolimod hydrochloride PO QD starting the day before chemotherapy, the day of chemotherapy, and 1 day after chemotherapy for 12 weeks.
Interventions:
  • Drug: Fingolimod
  • Drug: Fingolimod Hydrochloride
  • Other: Questionnaire Administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 6, 2019) 		20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2021
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03941743
Other Study ID Numbers  ICMJE MC18C1
NCI-2019-02741 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC18C1 ( Other Identifier: Mayo Clinic )
P30CA015083 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mayo Clinic
Study Sponsor  ICMJE Mayo Clinic
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Charles L Loprinzi Mayo Clinic
PRS Account Mayo Clinic
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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