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

CNS Metastases Clinical Trial

— BrainStorm  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04109131
• Other study ID #: IJB-BS-ODN-006
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2020
• Est. completion date: January 2028

Study information

• Verified date: January 2023
• Source: Jules Bordet Institute
• Contact: Nuria Kotecki
• Phone: +322541
• Email: nuria.kotecki[@]bordet.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: January 2028
• Est. primary completion date: January 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain Neoplasms
• CNS Metastases
• Neoplasm Metastasis

Intervention

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)
• 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
• 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
• 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)
• 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.

Locations

Country	Name	City	State
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Hôpital Erasme	Brussels
Belgium	Cliniques Universitaires St Luc	Bruxelles
Belgium	Grand Hôpital de Charleroi	Charleroi
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	UZ Brussel	Jette
Belgium	UZ Leuven	Leuven
Belgium	CHU Ambroise Paré	Mons
Belgium	CHU UCL Namur - Site de Sainte-Elisabeth	Namur
France	Centre Oscar Lambret	Lille
France	Institut Paoli-Calmettes	Marseille
France	Institut Curie	Paris
France	Institut Universitaire de Cancérologie AP-HP Sorbonne Université, Hopital Tenon	Paris
France	Centre Henri Becquerel	Rouen
France	CHU Strasbourg	Strasbourg
France	Institut Universitaire du Cancer - Oncopole	Toulouse
Luxembourg	Centre Hospitalier de Luxembourg	Luxembourg

Sponsors (5)

Lead Sponsor	Collaborator
Jules Bordet Institute	Bristol-Myers Squibb, Fondation Cancer, Luxembourg, La Fondation contre le cancer, Belgique, Les Amis de l'Institut Bordet

Countries where clinical trial is conducted

Belgium,  France,  Luxembourg, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	through study completion, approximately 96 months
Other	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	through study completion, approximately 96 months
Other	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.	through study completion, approximately 96 months
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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