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

• ClinicalTrials.gov Identifier: NCT04109131
• Recruitment Status: Recruiting
• First Posted: September 30, 2019
• Last Update Posted: May 17, 2022
• Sponsor: Jules Bordet Institute
• Collaborators: La Fondation contre le cancer, Belgique; Les Amis de l'Institut Bordet; Bristol-Myers Squibb; Fondation Cancer, Luxembourg
• Information provided by (Responsible Party): Jules Bordet Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
CNS Metastases	Other: Samples collection: Plasma; Other: Samples collection: CSF; Other: Samples collection: Non-CNS Metastatic Tumour Tissue; Other: Brain MRI; Other: Samples collection: Serum	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 600 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Brain Metastases Research Platform to Tackle the Challenge of CNS Metastases in Solid Tumours - BrainStorm Program
• Actual Study Start Date: July 1, 2020
• Estimated Primary Completion Date: January 2027
• Estimated Study Completion Date: January 2028

Arms and Interventions

Arm

Intervention/treatment

CNS metastases from solid tumours; 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; 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); Other Name: Blood for plasma preparation; Other: Samples collection: CSF; 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; Other Name: CSF sample; Other: Samples collection: Non-CNS Metastatic Tumour Tissue; 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; Other Name: Non-CNS Metastatic Tumour Tissue collection; Other: Brain MRI; 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); Other: Samples collection: Serum; 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.; Other Name: Blood for serum preparation

Outcome Measures

Primary Outcome Measures :

1. Better understanding of the epidemiology of CNS metastases from solid tumours [ Time Frame: through study completion, approximately 96 months ]

   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
2. Better understanding of the epidemiology of CNS metastases from solid tumours [ Time Frame: through study completion, approximately 96 months ]

   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

3. Better understanding of the epidemiology of CNS metastases from solid tumours [ Time Frame: through study completion, approximately 96 months ]

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

   - Overall survival

4. Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. [ Time Frame: through study completion, approximately 96 months ]

   To collect data regarding the biology of CNS metastases by investigating on:

   • Presence of CSF-ctDNA at diagnosis of CNS metastases
   • Presence of plasma ctDNA at diagnosis of CNS metastases
5. Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. [ Time Frame: through study completion, approximately 96 months ]
   • 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
6. Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. [ Time Frame: through study completion, approximately 96 months ]
   - 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
7. Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. [ Time Frame: through study completion, approximately 96 months ]
   - Standard analyses cytology and biochemistry analyses
8. Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. [ Time Frame: through study completion, approximately 96 months ]
   - Quantitative measurement of serum neuron-specific enolase

Other Outcome Measures:

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. [ Time Frame: through study completion, approximately 96 months ]

   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
2. 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. [ Time Frame: through study completion, approximately 96 months ]
   Levels of neuron specific enolase in blood
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. [ Time Frame: through study completion, approximately 96 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Age ≥ 18 years old
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
3. Female or Male

4. 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
5. Availability of either primary and/or non-CNS metastatic archival tumour tissue is mandatory for inclusion.
6. Willingness to undergo lumbar puncture at diagnosis of CNS metastases unless medical contra-indications
7. Predicted life expectancy > 3 months.
8. Women of childbearing potential must have a negative urine pregnancy test done within 28 days prior to enrolment
9. Effective contraception is in place for women of childbearing potential
10. Completion of all necessary screening procedures within 28 days prior to enrolment.

11. Signed Informed Consent form (ICF) obtained prior to any study related procedure.

    Inclusion criterion applicable to FRANCE only

12. Affiliated to the French Social Security System

Exclusion Criteria:

1. Pregnant and/or lactating women.
2. 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.

3. 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.

   Exclusion criterion applicable to FRANCE only

4. 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.

Contacts and Locations

Contacts

Contact: Nuria Kotecki; +322541 ext 7366; nuria.kotecki@bordet.be

Contact: Diane Delaroche; +322541 ext 7358; diane.delaroche@bordet.be

Locations

Belgium

Hôpital Erasme; Recruiting

Brussels, Belgium, 1070

Contact: Véronique Goblet +32 2 541 30 39 Veronique.Goblet@erasme.ulb.ac.be

Principal Investigator: Florence Lefranc, MD

Institut Jules Bordet; Recruiting

Bruxelles, Belgium, 1000

Contact: Sylvie Bartholomeus

Principal Investigator: Andrea Gombos

Cliniques Universitaires St Luc; Recruiting

Bruxelles, Belgium, 1200

Contact: Nathalie Blondeel

Principal Investigator: François Duhoux

Grand Hôpital de Charleroi; Recruiting

Charleroi, Belgium, 6000

Contact: Veronique Petre

Principal Investigator: Jean-Luc Canon

Universitair Ziekenhuis Gent; Recruiting

Gent, Belgium, 9000

Contact: Lore Vansteelant

Principal Investigator: Hannelore Denys

UZ Brussel; Recruiting

Jette, Belgium, 1090

Contact: Nadia Cappoen

Principal Investigator: Lore Decoster

UZ Leuven; Not yet recruiting

Leuven, Belgium, 3000

Contact: Inge Wauters ingeborg.wauters@uzleuven.be

Principal Investigator: Kevin Punie, MD

CHU Ambroise Paré; Recruiting

Mons, Belgium, 7000

Contact: Anna-Maria Barbuto

Principal Investigator: Stéphane Holbrechts

CHU UCL Namur - Site de Sainte-Elisabeth; Recruiting

Namur, Belgium, 5000

Contact: Dominique Crasson

Principal Investigator: Vincent Vanhaudenarde

France

Centre Oscar Lambret; Recruiting

Lille, France, 59020

Contact: Solene Charpentier s-charpentier@o-lambret.fr

Principal Investigator: Claire Cheymol, MD

Institut Paoli-Calmettes; Recruiting

Marseille, France, 13273

Contact: Anthony Lombardi LOMBARDIA@ipc.unicancer.fr

Principal Investigator: Anthony Goncalves, MD

Institut Curie; Recruiting

Paris, France, 75248

Contact: Anne Blondel anne.blondel@curie.fr

Principal Investigator: Edith Borcoman, MD

Centre Henri Becquerel; Recruiting

Rouen, France, 76038

Contact: Delphine Bridelance delphine.bridelance@chb.unicancer.fr

Principal Investigator: Florian Clatot, MD

CHU Strasbourg; Recruiting

Strasbourg, France, 67200

Contact: Anais Robert anais.robert@chru-strasbourg.fr

Principal Investigator: Philippe Barthelemy, MD

Institut Universitaire du Cancer - Oncopole; Recruiting

Toulouse, France, 31059

Contact: Marina Basmaison Basmaison.Marina@iuct-oncopole.fr

Principal Investigator: Jean-Pierre Delord, MD

Luxembourg

Centre Hospitalier de Luxembourg; Recruiting

Luxembourg, Luxembourg, 1445

Contact: Chouaib Mediouni chouaib.mediouni@lih.lu

Principal Investigator: Caroline Duhem, MD

Sponsors and Collaborators

Jules Bordet Institute

La Fondation contre le cancer, Belgique

Les Amis de l'Institut Bordet

Bristol-Myers Squibb

Fondation Cancer, Luxembourg

Investigators

• Study Chair: Nuria Kotecki, MD; Jules Bordet Institute

More Information

• Responsible Party: Jules Bordet Institute
• ClinicalTrials.gov Identifier: NCT04109131
• Other Study ID Numbers: IJB-BS-ODN-006
• First Posted: September 30, 2019
• Last Update Posted: May 17, 2022
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasm Metastasis; Brain Neoplasms; Neoplastic Processes; Neoplasms; Pathologic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases