A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours
ConditionCNS Metastases
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorJules Bordet Institute
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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).
Disqualifiers
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.
Trial design
Design model
Single group
Treatments tested in this trial
Samples collection: Plasma
Other interventionAt 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)
Samples collection: CSF
Other interventionPart 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
Samples collection: Non-CNS Metastatic Tumour Tissue
Other interventionPart 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
Brain MRI
Other interventionPart 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)
Samples collection: Serum
Other interventionAt 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.
Treatment groups
600 Participants
are divided into 1 treatment groupGroup A: CNS metastases from solid tumoursOther 5 interventions
Trial outcomes
Primary outcomes
1
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
Time frame
through study completion, approximately 96 months2
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
Time frame
through study completion, approximately 96 months3
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
Time frame
through study completion, approximately 96 months4
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
Time frame
through study completion, approximately 96 monthsOther outcomes
1
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.
To collect data regarding the biology of CNS metastases by investigating on : * Time to the first CNS event * Time to the second CNS event * Time to whole brain radiotherapy (WBR) * Time from the date of diagnosis of the first CNS event and the time of death by any cause
Time frame
through study completion, approximately 96 months2
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.
Levels of neuron specific enolase in blood
Time frame
through study completion, approximately 96 months3
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.
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. 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. Subsequently targeted gene sequencing will be performed on DNA samples from CSF and plasma in case of at least 5% tumour mutant allele frequency (MAF) and CNS metastases in case of surgery.
Time frame
through study completion, approximately 96 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Jules Bordet Institute
Lead sponsor
Fondation Cancer, Belgique
Collaborator
Les Amis
Collaborator
Bristol-Myers Squibb
Collaborator
Fondation Cancer, Luxembourg
Collaborator
Source ClinicalTrials.gov