Clinical trial NCT03941743: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Carcinoma
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2019-05-08
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Serially measured total sensory neuropathy scores
timeFrame: Baseline up to 18 months
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 18 months
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University/ Massey Cancer Center
state: Virginia
Study officials:
affiliation: Mayo Clinic
name: Charles L Loprinzi
role: PRINCIPAL_INVESTIGATOR
References: