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

Condition(s) studied

Investigational drug(s) / intervention(s)

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.

Study 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.

Eligibility

Primary outcome measure(s)

• Better understanding of the epidemiology of CNS metastases from solid tumours — 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
• Better understanding of the epidemiology of CNS metastases from solid tumours — 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
• Better understanding of the epidemiology of CNS metastases from solid tumours — 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
• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. — 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
• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. — through study completion, approximately 96 months
  To collect data regarding the biology of CNS metastases by investigating on: \- Presence of plasma ctDNA at diagnosis of CNS metastases
• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. — 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
• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. — 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
• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. — through study completion, approximately 96 months
  \- Standard analyses cytology and biochemistry analyses
• Better understand the biology of CNS metastases (brain and leptomeningeal carcinomatosis) using CSF-ctDNA as a surrogate endpoint for CNS tumour tissue DNA. — through study completion, approximately 96 months
  \- Quantitative measurement of serum neuron-specific enolase

Trial sites (17)

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