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

Official title

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

Overview

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.

Interventions

• 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 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 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 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.

Primary outcome measures

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

Eligibility criteria

Inclusion criteria

• 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
• Availability of either primary and/or non-CNS metastatic archival tumour tissue is mandatory for inclusion.
• Willingness to undergo lumbar puncture at diagnosis of CNS metastases unless medical contra-indications
• Predicted life expectancy > 3 months.
• Women of childbearing potential must have a negative urine pregnancy test done within 28 days prior to enrolment
• Effective contraception is in place for women of childbearing potential
• Completion of all necessary screening procedures within 28 days prior to enrolment.
• Signed Informed Consent form (ICF) obtained prior to any study related procedure.

Inclusion criterion applicable to FRANCE only

• Affiliated to the French Social Security System

Exclusion criteria

• 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.

Exclusion criterion applicable to FRANCE only

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

Belgium · 9 centers

• Institut Jules Bordet — Anderlecht
• Hôpital Erasme — Brussels
• Cliniques Universitaires St Luc — Brussels
• Grand Hôpital de Charleroi — Charleroi
• Universitair Ziekenhuis Gent — Ghent
• UZ Brussel — Jette
• UZ Leuven — Leuven
• CHU Ambroise Paré — Mons
• … and 1 more center

France · 7 centers

• Centre Oscar Lambret — Lille
• Institut Paoli-Calmettes — Marseille
• Institut Universitaire de Cancérologie AP-HP Sorbonne Université, Hopital Tenon — Paris
• Institut Curie — Paris
• Centre Henri Becquerel — Rouen
• Hopitaux Universitaires de Strasbourg — Strasbourg
• Institut Universitaire du Cancer - Oncopole — Toulouse

Luxembourg · 1 center

• Centre Hospitalier de Luxembourg — Luxembourg

Identifiers

NCT: NCT04109131 · IJB-BS-ODN-006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗