A Therapy Treatment Response Trial in Patients With Leptomeningeal Metastases ((LM) Using CNSide

Study Overview
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Brief Summary
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The FORESEE Study is a multi-center, prospective clinical trial enrolling patients with Breast or Non-Small Cell Lung Cancer (NSCLC) who have suspicious or confirmed Leptomeningeal Metastases (LM). Standard of Care methods to diagnose, or assess the treatment response of LM (Clinical Evaluation, MRI and Cytology) have limited sensitivity and specificity. This creates challenges for physicians to manage LM or determine the best course of treatment. CNSide, is a Laboratory Developed Test (LDT ) that is used commercially at the Physician's discretion in Biocept's CLIA certified, CAP accredited laboratory. CNSide can detect and quantify tumor cells in the CSF from patients with Breast Cancer or NSCLC having a suspicious or confirmed LM. The goal of the FORESEE Study is to evaluate the performance of CNSide in monitoring the LM's response to treatment and to assess the impact of CNSide on treatment decisions made by Physicians.

Detailed Description
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The FORESEE Study is a multi-center, prospective clinical trial enrolling patients with breast or Non-Small Cell Lung Cancer (NSCLC) who have suspicious or confirmed Leptomeningeal Metastases (LM). LM is a devastating complication of breast cancer and NSCLC and is diagnosed via clinical evaluation, MRI (with and without contrast of the brain and spine), and CSF Cytology. These methods have limited sensitivity and specificity. Furthermore, they lack the ability to quantitatively measure the LM's response to treatment. These hindrances create challenges for physicians to manage LM or to determine the best course of treatment. CNSide, is a Laboratory Developed Test (LDT ) that is analytically validated and run commercially in Biocept's CLIA certified, CAP accredited laboratory at the Physician's discretion. CNSide can detect and quantify tumor cells in the CSF from patients with Breast Cancer or NSCLC having a suspicious or confirmed LM. Data derived from case studies suggest that the detection of tumor cells in the CSF by CNSide can be used by Physicians to monitor the response of the LM tumor to treatment and improve the ability to make treatment decisions in patients with LM. Subjects enrolled onto the trial will be treated per Standard of Care. The diagnostic tests used to either diagnose LM, or monitor the LMs response to treatment will be Standard of Care, in combination with CNSide. The goal of the FORESEE Study is to further evaluate the performance of CNSide for LM in monitoring the LM's response to treatment and to assess the impact of CNSide on treatment decisions made by Physicians.

Official Title
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A Longitudinal Therapy Response Monitoring Study in Subjects With Leptomeningeal Metastases Using CNSide (CSF Tumor Cells) Compared to Standard of Care (CSF Cytology, Clinical Evaluation, and Imaging).

Conditions
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Leptomeningeal Metastasis, Leptomeningeal Disease, Leptomeningeal Neoplasms, Breast Cancer, Non-Small Cell Lung Cancer

Intervention / Treatment
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* Device: CNSide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects => 18 years of age All genders, races, or ethnic groups, Diagnosed with Breast Cancer or NSCLC who present with clinically suspected LM based on Investigator assessment of radiographic image, cytology, and clinical evaluation. Cytology positive and negative subjects will be included. Subjects willing to provide an Informed Consent. Subjects willing and able to undergo CSF or blood collection via Lumbar Puncture and Ommaya Reservoir as well as veni-puncture and shunt. Both patients with and without parenchymal brain metastases will be eligible as long as leptomeningeal metastases are suspected Subjects who previously had a diagnosis of Leptomeningeal Disease by Investigator assessment of radiographic image and clinical evaluation and cytology. Exclusion Criteria: Subjects who do not have cancer, Subjects with other types of tumors than breast or lung cancer Subjects diagnosed with a primary brain tumor Subjects who are unable to undergo lumbar puncture, a shunt or veni-puncture. Lack of suspicious LM based in imaging or clinical evaluation. Ordering the Commercial CNSide test while subject is on study Pregnant women and adults lacking capacity to consent for themselves
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Breast Cancer<br>Subjects with Breast Cancer of all subtypes and independent of Hormone status who have a confirmed or suspicious Leptomeningeal Metastasis by Investigator assessment of radiographic image and clinical evaluation and cytology | Device: CNSide<br>* The Cerebro-Spinal Fluid (CSF) of subjects enrolled into each cohort will be used for Standard of Care diagnostic assessments used for subjects with either confirmed or suspicious LM (Cytology, protein and glucose) in combination with CNSide analysis.<br>|
| Non-Small Cell Lung Cancer<br>Subjects with Non-Small Cell Lung Cancer of all subtypes who have a confirmed or suspicious Leptomeningeal Metastasis by Investigator assessment of radiographic image and clinical evaluation and cytology | Device: CNSide<br>* The Cerebro-Spinal Fluid (CSF) of subjects enrolled into each cohort will be used for Standard of Care diagnostic assessments used for subjects with either confirmed or suspicious LM (Cytology, protein and glucose) in combination with CNSide analysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the impact of CNSide on treatment decisions | The proportion of decision points during LM treatment in which the physician indicated that CNSide aided in their decision making. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate CNSide as a treatment response monitoring device for LM tumors | The correlation of changes in tumor cell number throughout treatment with clinical evaluation, cytology, and radiographic results. | 2 years | 
| The performance of CNSide of tumor cell detection in the CSF compared to cytology | The comparison of the sensitivity, specificity, PPV and NPV of CNSide to cytology in detection of tumor cells in the CSF (Cytology being the reference standard) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leptomeningeal Metastasis, Cerebro-Spinal Fluid, Liquid Biopsy, Tumor Cells