A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours

NCT04109131 | Recruiting

• 1 other identifier: IJB-BS-ODN-006
• Study Type: interventional
• Target: 600
• Locations: 3 countries
• Sites: 17

Brief Summary

Despite some encouraging data, systemic treatment of CNS metastases from solid tumors remains experimental. Better knowledge on the evolving epidemiology and biology of BM are key elements for the development of new treatment strategies and identification of promising therapeutic targets for new compounds. Further biological findings may help to better understand the heterogeneity between the primary tumor and the CNS metastases and to identify new targets for therapy thus improving patients' outcome. In this context, the Oncodistinct network and the Jules Bordet institute propose to build a multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm. The BrainStorm program will focus on patients with newly diagnosed non-CNS metastatic solid tumors with high risk of developing CNS metastases and will allow building a large clinico pathological database for CNS metastases including ctDNA analyzes from CSF samples. Substudies will be proposed at each time-period with the final objective to develop innovative treatment approaches and strategies.

Conditions

CNS Metastases

Outcome Measures

Primary Outcomes (9)

• Better understanding of the epidemiology of CNS metastases from solid tumours

  To collect data regarding the epidemiology of CNS metastases from solid tumours and identify risk factors for CNS metastases development, including: * Time to the first CNS event * Time to the second CNS after first treatment and subsequent CNS events

  through study completion, approximately 96 months

• Better understanding of the epidemiology of CNS metastases from solid tumours

  To collect data regarding the epidemiology of CNS metastases from solid tumours and identify risk factors for CNS metastases development, including:: \- Time to whole brain radiotherapy

  through study completion, approximately 96 months

• Better understanding of the epidemiology of CNS metastases from solid tumours

  To collect data regarding the epidemiology of CNS metastases from solid tumours and identify risk factors for CNS metastases development, including: \- Overall survival

  through study completion, approximately 96 months

• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA.

  To collect data regarding the biology of CNS metastases by investigating on: \- Presence of CSF-ctDNA at diagnosis of CNS metastases

  through study completion, approximately 96 months

• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA.

  To collect data regarding the biology of CNS metastases by investigating on: \- Presence of plasma ctDNA at diagnosis of CNS metastases

  through study completion, approximately 96 months

• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA.

  * quantification of plasma ctDNA and CSF-ctDNA using deep targeted NGS * deep targeted next-generation sequencing (NGS) on DNA samples from primary or non-CNS metastases as well as germline DNA samples and CNS metastases if surgery

  through study completion, approximately 96 months

• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA.

  \- A set of 1-3 point mutations (single nucleotide variants) will be selected for each subject based on the above analyses for the identification and quantification of plasma ctDNA and CSF-ctDNA using deep targeted NGS

  through study completion, approximately 96 months

• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA.

  \- Standard analyses cytology and biochemistry analyses

  through study completion, approximately 96 months

• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA.

  \- Quantitative measurement of serum neuron-specific enolase

  through study completion, approximately 96 months

Other Outcomes (3)

• Better understand the predictive value of NSE for the development of CNS metastases on subjects with newly diagnosed non-CNS metastatic solid tumours with high risk of developing CNS metastases.

  through study completion, approximately 96 months

• Better understand the predictive value of NSE for the development of CNS metastases on subjects with newly diagnosed non-CNS metastatic solid tumours with high risk of developing CNS metastases.

  through study completion, approximately 96 months

• Better understand the predictive value of NSE for the development of CNS metastases on subjects with newly diagnosed non-CNS metastatic solid tumours with high risk of developing CNS metastases.

  through study completion, approximately 96 months

Study Arms (1)

CNS metastases from solid tumours

OTHER

The study will be organised on three time-periods based on the time of the 1st CNS event: Part A - Pre-diagnosis period: before diagnosis of the 1st CNS event Part B - At 1st CNS diagnosis period Part C - Post diagnosis period: after the 1st CNS event

Other: Samples collection: Plasma; Other: Samples collection: CSF; Other: Samples collection: Non-CNS Metastatic Tumour Tissue; Other: Brain MRI; Other: Samples collection: Serum

Interventions

Samples collection: Plasma OTHER

At baseline Part A: * TNBC/ HER2+ BC: once a year * NSCLC/SCLC: every 4 months * Melanoma: every 6 months Part B: o As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis Part C: o Every 3 months (+/- 1 month)

Also known as: Blood for plasma preparation

CNS metastases from solid tumours

Samples collection: CSF OTHER

Part B: Mandatory CSF sampling at CNS diagnosis when clinically possible unless medically contra-indicated - As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis Part C: Additional CSF sampling in case CSF sampling is performed for routine clinical practice

Also known as: CSF sample

CNS metastases from solid tumours

Samples collection: Non-CNS Metastatic Tumour Tissue OTHER

Part B: Highly recommended non-CNS metastatic tumour tissue collection (1FFPE and 1 FT) at CNS metastases diagnosis (Part B) (NB: Bone lesions are excluded) - As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis

Also known as: Non-CNS Metastatic Tumour Tissue collection

CNS metastases from solid tumours

Brain MRI OTHER

Part A: * Brain MRI at inclusion is allowed within 45 days before enrolment * Brain MRI pre-CNS diagnosis (Part A) : HER2 BC/TNBC: once a year; NSCLC/SCLC: every 4 months; Melanoma: every 6 months (+/- 1 month) Part B: o As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis Part C: o Brain MRI post-CNS diagnosis (Part C): every 3 months (+/- 1 month window)

CNS metastases from solid tumours

Samples collection: Serum OTHER

At baseline Part A: * TNBC/ HER2+ BC: once a year * NSCLC/SCLC: every 4 months * Melanoma: every 6 months Part B: o As close as possible to the diagnosis of CNS metastases and no later than 6 weeks after diagnosis for cohorts 1-5.

Also known as: Blood for serum preparation

CNS metastases from solid tumours

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Female or Male
• Eligible for part A: Subjects (from cohorts 1 to 5) with newly diagnosed or up to 24 months from diagnosis of non-CNS metastases. Enrolment of exceptional cases surpassing 24 months from diagnosis will be allowed for up to 20% of subjects enrolled with HER2+ BC (cohort 2) and NSCLC harbouring driver mutations (cohort 3).
• Eligible for part B: Subjects (from cohorts 1 to 7) presenting with a first CNS event and not yet enrolled in the program
• Seven cohorts of subjects are defined in this prospective multicenter study:
• Cohort 1: Triple negative breast cancer (TNBC)
• Cohort 2: HER 2 positive breast cancer (HER2+ BC)
• Cohort 3: Non-small cell lung cancer (NSCLC)
• Cohort 4: Small cell lung cancer (SCLC)
• Cohort 5: Melanoma
• Cohort 6: Other solid tumours (apart from the above mentioned subtypes
• Cohort 7: Radiologically or cytologically confirmed leptomeningeal carcinomatosis
• Willingness to undergo lumbar puncture at diagnosis of CNS metastases unless medical contra-indications
• Predicted life expectancy \> 3 months.

You may not qualify if:

• Pregnant and/or lactating women.
• Previous or current malignancies of other histologies within the last 2 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
• Subject with a significant medical, neuro-psychiatric, or surgical condition, currently uncontrolled by treatment, which, in the principal investigator's opinion, may interfere with completion of the study.
• Vulnerable persons according to the article L.1121-6 of the Public Health Code, adults who are the subject of a measure of legal protection or unable to express their consent according to article L.1121-8 of the Public Health Code.

Sponsors & Collaborators

• Jules Bordet Institute: lead
• Fondation Cancer, Belgique: collaborator
• Les Amis: collaborator
• Bristol-Myers Squibb: collaborator
• Fondation Cancer, Luxembourg: collaborator

Study Sites (17)

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

Hôpital Erasme

Brussels, 1070, Belgium

RECRUITING

Cliniques Universitaires St Luc

Brussels, 1200, Belgium

RECRUITING

Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

UZ Brussel

Jette, 1090, Belgium

RECRUITING

UZ Leuven

Leuven, 3000, Belgium

RECRUITING

CHU Ambroise Paré

Mons, 7000, Belgium

RECRUITING

CHU UCL Namur - Site de Sainte-Elisabeth

Namur, 5000, Belgium

RECRUITING

Centre Oscar Lambret

Lille, 59020, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13273, France

RECRUITING

Institut Universitaire de Cancérologie AP-HP Sorbonne Université, Hopital Tenon

Paris, 75020, France

RECRUITING

Institut Curie

Paris, 75248, France

RECRUITING

Centre Henri Becquerel

Rouen, 76038, France

RECRUITING

Hopitaux Universitaires de Strasbourg

Strasbourg, 67200, France

RECRUITING

Institut Universitaire du Cancer - Oncopole

Toulouse, 31059, France

RECRUITING

Centre Hospitalier de Luxembourg

Luxembourg, 1445, Luxembourg

RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Nuria Kotecki, MD

  Jules Bordet Institute

  STUDY CHAIR

Central Study Contacts

Nuria Kotecki

CONTACT

+322541; nuria.kotecki@bordet.be

Diane Delaroche

CONTACT

+322541; diane.delaroche@bordet.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: September 30, 2019
• Study Start: July 1, 2020
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2029
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

LU (1); FR (7); BE (9)