STEP: Preoperative Stereotactic Radiosurgery for Brain Metastases

Sponsor

Centre Jean Perrin (Other)

Overall Status

Recruiting

CT.gov ID

NCT04503772

Collaborator

Groupement Interrégional de Recherche Clinique et d'Innovation (AURA) (Other)

Enrollment

Locations

Arm

28.8

Anticipated Duration (Months)

8.8

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Brain Metastases	Procedure: Preoperative SRS	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 4, 2021

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental arm (all patients) Patients will receive preoperative hypofractionated stereotactic radiosurgery (SRS). According to the association of french-speaking neuro-oncologists (ANOCEF) recommendations, total dose and fractionation will be 33 Gy in 3 fractions at the isocenter, 23.1 Gy in envelope (70% isodose), i.e. 30 Gy in growth tumor volume (GTV) envelope.) Surgery will take place within 3 days of the preoperative SRS.	Procedure: Preoperative SRS Patient will be treat with preoperative SRS and then surgery for brain metastases is realized within 3 days.

Arm

Intervention/Treatment

Experimental: Experimental arm (all patients)

Patients will receive preoperative hypofractionated stereotactic radiosurgery (SRS). According to the association of french-speaking neuro-oncologists (ANOCEF) recommendations, total dose and fractionation will be 33 Gy in 3 fractions at the isocenter, 23.1 Gy in envelope (70% isodose), i.e. 30 Gy in growth tumor volume (GTV) envelope.) Surgery will take place within 3 days of the preoperative SRS.

Procedure: Preoperative SRS

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

Outcome Measures

Primary Outcome Measures

Evaluation of 6-months local control rate after preoperative SRS [6 months after preoperative SRS (M6)]
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.

Secondary Outcome Measures

Evaluation of 1-year local control rate after preoperative SRS [12 months after preoperative SRS (M12)]
Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the RANO-BM criteria.
Evaluation of 1-year radionecrosis rate after preoperative SRS [12 months after preoperative SRS (M12)]
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)
Evaluation of overall survival [At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)]
defined as the time interval between the date of preoperative radiosurgery and the date of death from any cause.
Evaluation of acute (less than 3 months post preoperative SRS) and delayed toxicities (more than 3 months after preoperative SRS) [At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)]
They will be collected and graded according to the NCI-CTCAE v5.0 scale. An adverse event of grade ≥ 3 will be considered "severe".
Rate of leptomeningeal relapses [At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)]
According to cerebral MRI
Evaluation of cerebral distant control [At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)]
Follow by MRI
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)]
Evaluation of cognitive function [At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)]
Mini-mental state examination (MMSE)
Evaluation of quality of life [At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)]
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre Jean PERRIN	Clermont-Ferrand	Puy-de-Dôme	France	63800
2	CHU Grenoble Alpes	Grenoble		France	38700
3	Hospices Civils de Lyon	Lyon		France	69002
4	Centre Léon BÉRARD	Lyon		France	69373
5	Centre Hospitalier d'Annecy-Genevois	Metz-Tessy		France	74370
6	Institut de Cancérologie de l'Ouest	Saint-Herblain		France
7	Institut de cancérologie de la Loire Lucien Neuwirth	Saint-Priest-en-Jarez		France	42270
8	Institut de cancérologie Strasbourg Europe (ICANS)	Strasbourg		France	67000