Neoplasms

Skin and Connective Tissue Diseases

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Breast Neoplasms

Carcinoma

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Paclitaxel

Albumin-Bound Paclitaxel

Fingolimod Hydrochloride

Immunosuppressive Agents

Immunologic Factors

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

Fingolimod

Questionnaire Administration

Charles L Loprinzi

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.

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.

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

Prevention of Paclitaxel-Associated Neuropathy With Fingolimod: a Pilot Trial

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.

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.

National Cancer Institute (NCI)

Mayo Clinic

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Glioblastoma

Glioma

Lymphopenia

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Anaplastic Astrocytoma

Neuroepithelioma

Temozolomide

Five evaluable patients with newly diagnosed high grade gliomas who will undergo standard concomitant radiation and temozolomide followed by adjuvant temozolomide will be accrued to this open-label, single arm, safety study. Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy. Fingolimod will be administered at 0.5 mg every day for the first two weeks. Beginning the third week, they will take fingolimod on Monday, Wednesday and Friday until the end of radiotherapy or until the 28th dose, whichever comes first.

Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy.

Stuart Grossman, MD

A recent prospective multicenter study by Dr. Grossman demonstrated that 40% of patients with high grade glioma undergoing radiation and chemotherapy developed severe and persistent lymphopenia (CD4 counts \<200 cells/mm3). This lymphopenia lasted for twelve months following radiation treatment and on multivariate analysis was associated with shorter survival. Our group has data that strongly suggests that this lymphopenia is secondary to the inadvertent radiation of circulating lymphocytes as they pass through the radiation beam. Investigators propose the use of FDA approved for multiple sclerosis, fingolimod to signal lymphocytes to leave the circulation prior to the initiation of radiation. It is a functional antagonist of the sphingosine-1-phosphate receptor (S1PR) pathway and prevents lymphocyte egress from secondary lymphoid organs.

Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy. The primary objective is to evaluate if fingolimod can be safely combined with radiation and temozolomide. Secondary endpoint is total lymphocyte counts (TLC) for the proposed study participants. Investigators expect that patients receiving radiation and temozolomide plus fingolimod have a recovery of lymphocyte counts to 80% of baseline within four months, reference to historical control in which sustained lymphopenia lasted for twelve months.

Five evaluable patients with newly diagnosed high grade gliomas who will undergo standard concomitant radiation and temozolomide followed by adjuvant temozolomide will be accrued to this open-label, single arm, safety study. Oral fingolimod will be given 1 week prior to the initiation of concurrent radiation and temozolomide and will be discontinued immediately upon completion of the six weeks of therapy.

The primary objective is to evaluate if fingolimod can be safely combined with radiation and temozolomide. This standard chemoradiation causes 40% of patients to develop severe lymphopenia two months after initiation of therapy. Investigators expect that when this is combined with fingolimod, virtually all patients will have severe lymphopenia two months after beginning treatment. Investigators will determine if these patients who routinely receive pneumocystis jiroveci prophylaxis develop other severe opportunistic infections that would prohibit further evaluation of this novel treatment approach. Primary endpoint is incidence of greater than or equal to Grade III infections attributable to fingolimod-induced lymphopenia defined by the NIH/NCI Common Terminology Criteria for Adverse Events (CTCAE) within four months of starting fingolimod.

The secondary objective is to obtain preliminary information regarding the ability of fingolimod to reduce radiation-related lymphopenia three months after stopping fingolimod. The NIH funded Adult Brain Tumor Consortium (ABTC) followed total lymphocyte and CD4 counts in 96 patients after treatment with radiation and temozolomide. The severe lymphopenia (CD4 count less than 200/mm3) lasted for twelve months in this historical control. Secondary endpoint is total lymphocyte counts (TLC) for the proposed study participants. These will be compared with patient level data on TLC from an historical cohort obtained from the ABTC. Investigators expect that patients receiving radiation and temozolomide plus fingolimod have a recovery of lymphocyte counts to 80% of baseline within four months, reference to historical control in which sustained lymphopenia lasted for twelve months.

Investigators will also obtain laboratory analysis on lymphocyte subtypes and cytokine levels (CD3, CD4, CD8, IL-7, TGF-Beta, etc.). Routine care for high grade gliomas includes weekly Heme-8 and absolute lymphocyte count. Research blood will be obtained at 2 weeks prior to chemoradiation and again at weeks 6, 10, 18, 26 and 46. Patients will be on study for approximately one year.

A Safety Study of Fingolimod With Radiation and Temozolomide in Newly Diagnosed High Grade Glioma

Incidence of greater than or equal to Grade III infections attributable to fingolimod-induced lymphopenia defined by the NIH/NCI Common Terminology Criteria for Adverse Events (CTCAE)

Total lymphocyte counts (TLC) for study participants compared to TLC for historical control

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer	NCT03941743	Breast Carcinom...	Fingolimod Fingolimod Hydr... Questionnaire A...	18 Years -	Mayo Clinic
A Safety Study of Fingolimod With Radiation and Temozolomide in Newly Diagnosed High Grade Glioma	NCT02490930	Glioblastoma Anaplastic Astr...	Fingolimod	18 Years -	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Fingolimod in Preventing Paclitaxel-Associated Neuropathy in Patients With Breast Cancer	NCT03941743	Breast Carcinom...	Fingolimod Fingolimod Hydr... Questionnaire A...	18 Years -	Mayo Clinic

Spots Global Cancer Trial Database for fingolimod

Every month we try and update this database with for fingolimod cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for fingolimod

Every month we try and update this database with for fingolimod cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for fingolimod cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.