Identification of Risk Factors for Brain Recurrence in Patients With HER2-positive Localised Breast Cancer

HER2-positive Breast Cancer Clinical Trial

— CRANIUM  

Official title:

Identification of Risk Factors for Brain Recurrence in Patients With HER2-positive Localised Breast Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06358625
• Other study ID #: 2023-4-1-001
• Status: Not yet recruiting
• Start date: April 30, 2024
• Est. completion date: April 30, 2031

Study information

• Verified date: April 2024
• Source: Center Eugene Marquis
• Contact: Valérie JOLAINE, Dr
• Phone: (0)299253036
• Email: v.jolaine[@]rennes.unicancer.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

HER2 gene amplification, detected in 20% to 30% of breast cancers, was a poor prognostic factor before the advent of anti-HER2 therapies. In the early 2000s, trastuzumab revolutionised the management of patients with HER2-positive (HER2+) breast cancer in the metastatic and localised stages of the disease.

At the time of diagnosis of metastatic disease, 7-11% of patients have brain metastases, with (70% of cases) or without symptoms (30% of cases). In the absence of brain metastases, 30% to 50% of patients will develop brain metastases within the first two years of treatment, depending on whether the disease is hormone receptor positive (HR+) or negative (HR-).

The presence of brain metastases is the most important prognostic factor. The neurological symptoms caused by the presence of these lesions, but also by the local treatments offered, affect patients' quality of life, although improvements in surgical and radiotherapy techniques have significantly reduced the need for particularly toxic whole brain radiotherapy.

International guidelines do not recommend systematic brain MRI in the absence of neurological symptoms, either in the adjuvant or metastatic stages of this disease. However, there may be a role for more systematic and earlier screening for cerebral recurrence, as single cerebral recurrences without extracranial involvement are common and the new anti-HER2 agents (i.e. tucatinib, an anti-HER2 tyrosine kinase inhibitor, and T-Dxd) have shown significant objective response rates in cerebral metastases.

To date, no clinical or histological prognostic factor (proliferation index, HR expression, etc.) has been used to identify a population of patients at high risk of cerebral relapse, allowing monitoring and treatment to be personalised.

New tools for these indications would significantly modify our clinical practice, allowing the identification of a subpopulation at high risk of cerebral recurrence, suitable for increased monitoring and therapeutic adjustment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 120
• Est. completion date: April 30, 2031
• Est. primary completion date: April 30, 2031
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years old

• be a female patient

• Patients with histologically proven HER2-positive invasive breast cancer (IHC 3+ or 2+ with positive SISH),

• Neoadjuvant chemotherapy and intra-tumour clips indicated at the multidisciplinary consultation meeting (RCP).

• Signed Informed Consent Form

Exclusion Criteria:

• pregnant or breast-feeding women

• Have had a haematoma requiring level II analgesics at the time of the diagnostic biopsy.

• Known coagulation disorders

• Individual deprived of liberty or placed under the authority of a tutor, or a currator

• Not be affiliated to a social security regimen

Related Conditions & MeSH terms

• Breast Neoplasms
• HER2-positive Breast Cancer
• Recurrence

Intervention

Other:
• Pre-treatment biopsy
A breast biopsy is performed just before the "clip" is placed in the tumour and additional blood samples are performed.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Center Eugene Marquis

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Transcriptomic profile change of HER2+ primary breast tumours before any treatment	comparison of the transcriptomic profile of HER2+ primary breast tumours before any treatment of patients who will develop brain metastases within 5 years with patients who will not develop them	At inclusion
Secondary	Transcriptomic profile change on circulating tumour DNA (ctDNA)	High-throughput sequencing (NGS) of a panel of genes previously identified by transcriptomic analysis	At baseline, Year 1; Year2; Year3, Year4; Year 5, at relapse