Analyses of Exosomes in the Cerebrospinal Fluid for Breast Cancer Patients With Suspicion of Leptomeningeal Metastasis.

Not Applicable

Withdrawn

• Conditions: Breast Cancer; Leptomeningeal Metastasis
• Interventions: Procedure: Cerebrospinal fluid and blood sample collection at the initial diagnostic assessment; Procedure: Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are "Lack of evidence" according to EANO-ESMO classification; Procedure: Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are "confirmed", "probable" or "possible", leading to leptomeningeal metastase specific treatment

• Registration Number: NCT03974204
• Lead Sponsor: Centre Oscar Lambret

Brief Summary

This is a multicenter, interventional, prospective study among breast cancer patients with a suspicion of metastatic meningitis. The current study aims to assess the use of proteomic profile issued from cerebrospinal fluid microvesicles for diagnosis of leptomeningeal metastases.

Detailed Description

The aim of this study is to describe the association between the initial proteomic profile issued from cerebrospinal fluid microvesicles and the initial cytological analysis of the cerebrospinal fluid in breast cancer patients with a suspicion of metastatic meningitis.

Other objectives of the study include:

* Describing the association between the initial proteomic profile and:

* the histological types and hormonal receptors status of the breast cancer,

* the likelihood of leptomeningeal metastasis according to the EANO-ESMO classification (Lack of evidence / possible / probable / confirmed) ,

* the likelihood of leptomeningeal metastasis according to the EANO-ESMO classification, combined with histological type and hormonal receptors status.

* Evaluate the prognostic value of the proteomic profiling for overall survival, according to the EANO-ESMO classification and other known prognosis factors, in patients classified "possible", "probable" or "confirmed" leading to leptomeningeal metastases specific treatment,

* Evaluate the impact of the evolution of the proteomic profile a month after the start of this treatment on the overall survival, in patients with leptomeningeal metastases specific treatment,

* Evaluate the association between the proteomic profile and the EANO-ESMO classification at least 3 months after the initial EANO-ESMO classification,

* Evaluate the evolution of the proteomic profile 3 months after the initial EANO-ESMO classification, in patients initially classified "lack of evidence", broadly and according to the evolution of cytology, the administered treatments and to the EANO-ESMO response if applicable,

* Compare the proteomic profiles issued from cerebrospinal fluid and blood

Study Timeline

• Study First Submitted: 2019-05-31
• Study First Submitted QC: 2019-06-03
• Study First Posted: 2019-06-04
• Study Start: 2019-07
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-05
• Last Update Posted: 2021-10-12
• Primary Completion: 2022-10
• Study Completion: 2023-10

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Female
• Target Recruitment: Not specified

Inclusion Criteria

• Patient with histologically proven breast cancer
• Patient with suspected metastatic leptomeningitis
• Age ≥ 18 years
• Patient covered by the French social security regime
• Signed written informed consent

Exclusion Criteria

• History of cancer other than the one being treated
• Contraindication to carrying out the lumbar puncture or cerebrospinal MRI
• Pregnant or breastfeeding patient

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Cerebrospinal fluid and Blood sample collection	Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are "Lack of evidence" according to EANO-ESMO classification	Collection of cerebrospinal fluid and blood samples: * At initial diagnostic assessment; * 1 month and 3 months after initial diagnostic assessment, for patients classified "possible", "probable" or "confirmed" according to EANO-ESMO classification, leading to specific leptomeningeal metastase treatment; * In case of symptoms leading to leptomeningeal metastase suspicion and at least 3 months after diagnostic assessment, for patients classified "lack of evidence" according to EANO-ESMO classification.
Cerebrospinal fluid and Blood sample collection	Cerebrospinal fluid and blood sample collection if conclusions of initial diagnostic assessment are "confirmed", "probable" or "possible", leading to leptomeningeal metastase specific treatment	Collection of cerebrospinal fluid and blood samples: * At initial diagnostic assessment; * 1 month and 3 months after initial diagnostic assessment, for patients classified "possible", "probable" or "confirmed" according to EANO-ESMO classification, leading to specific leptomeningeal metastase treatment; * In case of symptoms leading to leptomeningeal metastase suspicion and at least 3 months after diagnostic assessment, for patients classified "lack of evidence" according to EANO-ESMO classification.
Cerebrospinal fluid and Blood sample collection	Cerebrospinal fluid and blood sample collection at the initial diagnostic assessment	Collection of cerebrospinal fluid and blood samples: * At initial diagnostic assessment; * 1 month and 3 months after initial diagnostic assessment, for patients classified "possible", "probable" or "confirmed" according to EANO-ESMO classification, leading to specific leptomeningeal metastase treatment; * In case of symptoms leading to leptomeningeal metastase suspicion and at least 3 months after diagnostic assessment, for patients classified "lack of evidence" according to EANO-ESMO classification.

Primary Outcome Measures

Name	Time	Method
Cytology of cerebrospinal fluid at diagnosis	Up to 1 week	Results of cytological analysis of cerebrospinal fluid will be "Positive", "negative", "equivocal".
Proteomic profiles issued from cerebrospinal fluid at diagnosis	Up to 1 week	Proteomic profile will be obtained by bioinformatic analysis of cerebrospinal fluid.

Secondary Outcome Measures

Name	Time	Method
Likehood of leptomeningeal metastasis according to the EANO-ESMO classification.	Up to 3 months after the intial diagnosis	EANO-ESMO classification is obtained by searching clinical symptoms, cancer cells in the cerebrospinal fluid (obtained by lumbar puncture), signs in RMI. The likehood of leptomeningeal metastasis is: * Lack of evidence,; * Possible,; * Probable,; * Confirmed.
Proteomic profiles issued from cerebrospinal fluid	Up to 3 months	Proteomic profile will be obtained by bioinformatic analysis of cerebrospinal fluid: * 1 month and 3 month after the start of a specific treatment of the leptomeningeal metastasis, if applicable,; * 3 months after the initial diagnosis of leptomeningeal metastasis if the likehood of leptomeningeal metastasis is "lack of evidence".
Overall survival	Time from date of registration to date of death regardless of the cause, assessed up to 1 year	Overall survival is defined as time from date of registration to date of death regardless of the cause.
Histological subtype	Before registration in study	Histological subtype will be subdivised as invasive ductal breast carcinoma, invasive lobular breast carcinoma, other brest carcinoma.
Hormonal receptors status	Before registration in study	Hormonal receptors status will be subdivised as: * Positive hormonal receptors / Positive HER2; * Positive hormonal receptors / Negative HER2; * Negative hormonal receptors / Positive HER2; * Triple negative
Proteomic profiles issued from blood	Up to 3 months after the intial diagnosis	Proteomic profile will be obtained by bioinformatic analysis of blood.

Trial Locations

Locations (2)

Centre Oscar Lambret; 🇫🇷 Lille, Hauts-de- France, France

Centre Hospitalier Régional Universitaire de Lille; 🇫🇷 Lille, Hauts-de-France, France