Preoperative Stereotactic Radiosurgery for Brain Metastases

Brain Metastases Clinical Trial

— STEP  

Official title:

Phase II Study to Assess Preoperative Hypofractionated Stereotactic Radiotherapy of Brain Metastases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04503772
• Other study ID #: 2020-A00403-36
• Secondary ID: 20.06.16-36701
• Status: Recruiting
• Phase: Phase 2
• Start date: February 4, 2021
• Est. completion date: August 2025

Study information

• Verified date: June 2024
• Source: Centre Jean Perrin
• Contact: Angeline GINZAC COUVÉ, PhD
• Phone: 0463663337
• Email: angeline.ginzac[@]clermont.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

STEP is a French multicentre, prospective, non-randomized, phase II study designed to assess 6-months local control after pre-operative stereotactic radiosurgery (SRS) for patients with brain metastases

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: August 2025
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• = 4 distinct brain metastases, one with surgical indication

• Diagnosis of primary histologically proven breast, digestive or non-small cells lung cancer

• = 5 cm larger diameter

• Karnofsky performance status = 70

• No contraindication for MRI

• Possibility for the patient to be treat with both surgery and stereotactic radiotherapy

• = 18 years old

• Estimated overall survival = 6 months according to diagnosis specific - graded prognostic assessment (DS GPA)

• Written inform consent signed

• Affiliation to the French social security system

• For women of childbearing age including those on luteinizing hormone-releasing hormone (LH-RH) agonists for ovarian suppression: inclusion negative serum pregnancy test (= 7 days prior to the start of preoperative stereotactic radiosurgery (SRS).

Exclusion Criteria:

• Lymphoma, leukaemia, multiple myeloma, germinal tumours or cerebral primary cancer

• Metastases from small-cells lung cancer, kidney cancer, melanoma or sarcoma

• Mass effect with deflection = 5 mm from median line or hydrocephaly or compression 4th ventricle, patient neurologically unstable, need for emergency decompressive surgery

• > 4 brain metastases

• Contraindication to anaesthesia, MRI or gadolinium injection

• Proximity of the tumour with organs at risk which do not allow the prescribed dose to be reached in the envelope

• Pregnant or breastfeeding woman

• Anti vascular endothelial growth factor (VEGF) within 6 weeks before treatment

• Documented leptomeningeal injury

• History of irradiation of the encephalon in toto

• History of stereotactic radiotherapy on metastasis to be operated on

• Non-candidate patient for surgery

• Surgical delay > 3 days compared to stereotactic radiotherapy

• Estimated survival < 6 months by DS GPA

• Patient under guardianship or curators

• Psychological disorder (cognitive disorders, mental alertness, etc.) or social (deprivation of liberty by judicial or administrative decision) or geographical reasons that may compromise medical monitoring of the trial or compliance with treatment

• Woman of childbearing age without effective contraception

• Patient participating in another intervention study within 4 weeks prior to inclusion

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Procedure:
• Preoperative SRS
Patient will be treat with preoperative SRS and then surgery for brain metastases is realized within 3 days.

Locations

Country	Name	City	State
France	Centre Jean PERRIN	Clermont-Ferrand	Puy-de-Dôme
France	CHU Grenoble Alpes	Grenoble
France	Centre Léon BÉRARD	Lyon
France	Hospices Civils de Lyon	Lyon
France	Centre Hospitalier d'Annecy-Genevois	Metz-Tessy
France	Institut de Cancérologie de l'Ouest	Saint-Herblain
France	Institut de cancérologie de la Loire Lucien Neuwirth	Saint-Priest-en-Jarez
France	Institut de cancérologie Strasbourg Europe (ICANS)	Strasbourg

Sponsors (2)

Lead Sponsor	Collaborator
Centre Jean Perrin	Groupement Interrégional de Recherche Clinique et d'Innovation (AURA)

Country where clinical trial is conducted

France, 

References & Publications (1)

Ginzac A, Dupic G, Brun L, Molnar I, Casile M, Durando X, Verrelle P, Lemaire JJ, Khalil T, Biau J. Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial. BMC Cancer. 2021 Jul 28;21(1):864. doi: 10.1186/s12885-021-08602-0. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of 6-months local control rate after preoperative SRS	Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria.	6 months after preoperative SRS (M6)
Secondary	Evaluation of 1-year local control rate after preoperative SRS	Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the RANO-BM criteria.	12 months after preoperative SRS (M12)
Secondary	Evaluation of 1-year radionecrosis rate after preoperative SRS	Radionecrosis is defined either histologically post-operatively according to the anatomopathological report or in the absence of salvage surgery by the appearance or increase of gadolinium contrast on T1 MRI sequences associated with an increase in the cerebral brain volume (CBV) ratio (brain blood volume of the tumour / brain blood volume of the non-tumour white matter) of less than 2 on perfusion MRI sequences and/or a standard uptake volume (SUV max) of less than 1, 59 on positron emission tomography (PET) scanners at 6-fluoro-[18 fluoro]-L-dihydroxyphenylalanine (F-DOPA)	12 months after preoperative SRS (M12)
Secondary	Evaluation of overall survival	defined as the time interval between the date of preoperative radiosurgery and the date of death from any cause.	At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
Secondary	Evaluation of acute (less than 3 months post preoperative SRS) and delayed toxicities (more than 3 months after preoperative SRS)	They will be collected and graded according to the NCI-CTCAE v5.0 scale. An adverse event of grade = 3 will be considered "severe".	At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
Secondary	Rate of leptomeningeal relapses	According to cerebral MRI	At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
Secondary	Evaluation of cerebral distant control	Follow by MRI	At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
Secondary	Determination of predictive factors for local brain control, complication and prognosis factors for survival		At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
Secondary	Evaluation of cognitive function	Mini-mental state examination (MMSE)	At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)
Secondary	Evaluation of quality of life	European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30)	At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

External Links

•   Study protocol article