Tumor Treating Fields for the Treatment of Leptomeningeal Metastases of the Spine in Patients With Breast Cancer

Study Overview
=================
Brief Summary
-----------------
This clinical trial evaluates the safety and feasibility of tumor treating fields (TTF) in the treatment of spinal leptomeningeal disease in patients with breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Patients wear the portable Novo TTF-200T device that produces electric fields to target areas on the body to stop the growth of tumor cells. The information from this study will help researchers develop a better treatment for leptomeningeal metastases in the future.

Detailed Description
-----------------
PRIMARY OBJECTIVE: I. To evaluate the safety and feasibility of TTFields in treatment of the spinal component of leptomeningeal metastases. SECONDARY OBJECTIVE: I. To document any preliminary signals of activity, as measured by radiographic and clinical response, or durable stability of objective neurologic examination, utilizing Leptomeningeal Assessment in Neuro-Oncology (LANO) criteria, magnetic resonance imaging (MRI) imaging, cerebrospinal fluid (CSF) cytologic examination, and patient-reported symptom assessment (M. D. Anderson Symptom Inventory [MDASI]-spine module). OUTLINE: Patients have transducer arrays applied and digital photographs taken of placement on study. Patients wear the NovoTTF-200T portable system on study. Patients also undergo MRI and may undergo lumbar puncture (LP) during screening and on study.

Official Title
-----------------
Pilot Feasibility Study of Tumor Treating Fields in Treatment of Leptomeningeal Metastases From Breast Carcinoma Involving the Spine

Conditions
-----------------
Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Metastatic Malignant Neoplasm in the Leptomeninges

Intervention / Treatment
-----------------
* Other: Digital Photography
* Procedure: Lumbar Puncture
* Procedure: Magnetic Resonance Imaging
* Device: Medical Device Usage and Evaluation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age >= 18 Prior tissue diagnosis of breast cancer Confirmed diagnosis of leptomeningeal metastases (LM) with positive cerebrospinal fluid (CSF) cytology for malignancy and meningeal enhancement (type 1A, 1B, and 1C) Radiographic evidence on MRI of leptomeningeal enhancement within the cervical, thoracic or lumbar spine on spinal MRI Life expectancy of at least 6 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, 2, or 3 Recovery from any neurotoxic effects of prior therapy Platelet count greater than 25,000/mm^3, and absolute neutrophil count (ANC) greater than 0.5 mm^3 Patients must have adequate liver function, total bilirubin < 2.5 mg%, unless elevated total bilirubin is due to elevated indirect bilirubin from known Gilbert's disease, aspartate aminotransferase (AST) =< 3.5 times upper limits of normal; adequate renal function (calculated estimated glomerular filtration rate [eGFR] >= 30%) Patients or legal medical representative must provide written informed consent Patients must have suitable body habitus for placement of transducer arrays Patients must be willing to wear the device for at least 18 hours a day (averaged over monthly) Patients must be willing to return for the scheduled evaluations and perform the required assessments Patients are without other disease or situation which would significantly compromise adequate assessment of safety and feasibility of the TTF Patient willing to start a study treatment with TTF =< 14 days from registration Exclusion Criteria: Concomitant therapy: Must not be receiving concurrent high-dose methotrexate (>= 3 g/m^2), high dose thiotepa, or high-dose cytarabine (>= 3 g/m^2). Any other systemic chemotherapy, targeted treatment, hormonal or immunotherapy directed at the primary systemic malignancy is permitted Must not have received radiation therapy (RT) to the brain or spinal cord within 2 weeks of initiation of TTF Must be at least 1 week from cessation of any prior intrathecal chemotherapy Women of childbearing age who are pregnant or lactating. (Male and female patients who are fertile must be willing to use an effective means of birth control to avoid pregnancy) Patients with uncontrolled or untreated infection including active hepatitis, and human immunodeficiency virus (HIV) Patients receiving any other investigational agents and must not have received any other investigational agent within 14 days prior to registration. The 14-day period should be extended if the investigational agent is known to have delayed toxicity Patients known to be allergic to the hydrophilic gel utilized for transducer attachment Patients with surgical hardware within the planned area of treatment in the spine (e.g., titanium rods, screws, fixation devices)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (TTFields, digital photos)<br>Patients have transducer arrays applied and digital photographs taken of placement on study. Patients wear the NovoTTF-200T portable system on study. Patients also undergo MRI and may undergo LP during screening and on study. | Other: Digital Photography<br>* Digital photographs taken of array placement<br>Procedure: Lumbar Puncture<br>* Undergo LP<br>* Other names: Spinal Tap;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Device: Medical Device Usage and Evaluation<br>* Transducer arrays applied and wear NovoTTF-200T<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of significant toxicity of tumor treating fields (TTFs) | Will be measured by grade 3 or greater non-hematologic adverse events that persist despite temporary interruption of treatment and maximal medical management. (i.e. grade 3 or greater non-hematologic toxicities that are not responsive to cessation of treatment and administration of supportive care). Toxicities will be assessed using Cancer Therapy Evaluation Program Active Version Common Terminology Criteria for Adverse Events. | Up to 3 years | 
| Feasibility of TTFs - estimated the number of patients who are unable to complete at least 30 days of TTF therapy | Will be estimated the number of patients who are unable to complete at least 30 days of TTF therapy (a composite average for the 30 days of at least 50% of array 'on' time) divided by the total number of evaluable patients. | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Preliminary signals of activity by Leptomeningeal Assessment in Neuro-Oncology scoring and the M. D. Anderson Symptom Inventory -spine module data (MDASI-SP) | Descriptive analyses will be performed. Data evaluated will include: cerebral spinal fluid (CSF) cytologic response; magnetic resonance imaging radiographic response within the TTF field. | Up to 3 years | 
| Preliminary signals of activityby Leptomeningeal Assessment in Neuro-Oncology scoring and the M. D. Anderson Symptom Inventory -spine module data (MDASI-SP); and adverse events | Descriptive analyses will be performed. Data evaluated will include: Time to CSF cytologic response (defined as the date of initiation of TTF to the last date of three consecutive negative CSF cytologic examinations). | Up to 3 years | 
| Preliminary signals of activity (defined as either suspicious or positive cytology). | Descriptive analyses will be performed. Data evaluated will include: Duration of cytologic response (time from the date of the third consecutive negative CSF to CSF cytologic relapse (defined as either suspicious or positive cytology). | Up to 3 years | 
| Preliminary signals of activity by Leptomeningeal Assessment in Neuro-Oncology scoring and the M. D. Anderson Symptom Inventory -spine module data (MDASI-SP) and adverse events. | Descriptive analyses will be performed. Data evaluated will include: Neurologic progression-free survival; duration of TTF treatment; overall survival from start of TTF. | Up to 3 years |