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Preoperative Stereotactic Radiosurgery for Brain Metastases (STEP)

Primary Purpose

Brain Metastases

Status

Recruiting

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

Preoperative SRS

About this trial

This is an interventional treatment trial for Brain Metastases focused on measuring brain metastases, preoperative stereotactic radiosurgery, local control, radionecrosis, overall survival

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Centre Jean PERRINRecruiting
CHU Grenoble AlpesRecruiting
Hospices Civils de LyonRecruiting
Centre Léon BÉRARDRecruiting
Centre Hospitalier d'Annecy-GenevoisRecruiting
Institut de Cancérologie de l'OuestRecruiting
Institut de cancérologie de la Loire Lucien Neuwirth
Institut de cancérologie Strasbourg Europe (ICANS)Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Experimental arm (all patients)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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)

Evaluation of overall survival

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)

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

According to cerebral MRI

Evaluation of cerebral distant control

Follow by MRI

Determination of predictive factors for local brain control, complication and prognosis factors for survival

Evaluation of cognitive function

Mini-mental state examination (MMSE)

Evaluation of quality of life

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30)

Full Information

NCT ID

NCT04503772

First Posted

August 4, 2020

Last Updated

February 7, 2023

Sponsor

Centre Jean Perrin

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT04503772

Brief Title

Preoperative Stereotactic Radiosurgery for Brain Metastases

Acronym

STEP

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 4, 2021 (Actual)

Primary Completion Date

February 2025 (Anticipated)

Study Completion Date

August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Jean Perrin

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain Metastases

Keywords

brain metastases, preoperative stereotactic radiosurgery, local control, radionecrosis, overall survival

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Experimental arm (all patients)

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Preoperative SRS

Intervention Description

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

Primary Outcome Measure Information:

Title

Evaluation of 6-months local control rate after preoperative SRS

Description

Time Frame

6 months after preoperative SRS (M6)

Secondary Outcome Measure Information:

Title

Evaluation of 1-year local control rate after preoperative SRS

Description

Local recurrence is defined as the onset or progression of nodular contrast grafting within the resection cavity according to the RANO-BM criteria.

Time Frame

12 months after preoperative SRS (M12)

Title

Evaluation of 1-year radionecrosis rate after preoperative SRS

Description

Time Frame

12 months after preoperative SRS (M12)

Title

Evaluation of overall survival

Description

defined as the time interval between the date of preoperative radiosurgery and the date of death from any cause.

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

Title

Evaluation of acute (less than 3 months post preoperative SRS) and delayed toxicities (more than 3 months after preoperative SRS)

Description

They will be collected and graded according to the NCI-CTCAE v5.0 scale. An adverse event of grade ≥ 3 will be considered "severe".

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

Title

Rate of leptomeningeal relapses

Description

According to cerebral MRI

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

Title

Evaluation of cerebral distant control

Description

Follow by MRI

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

Title

Determination of predictive factors for local brain control, complication and prognosis factors for survival

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

Title

Evaluation of cognitive function

Description

Mini-mental state examination (MMSE)

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

Title

Evaluation of quality of life

Description

European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Core 30 (C30)

Time Frame

At each follow-up visits after preoperative SRS : +3 months (M3); +6 months (M6); +9 months (M9); +12 months (M12)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Angeline GINZAC COUVÉ, PhD

Phone

0463663337

Ext

+33

angeline.ginzac@clermont.unicancer.fr

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lucie BRUN, MD

Organizational Affiliation

Centre Jean Perrin

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Jean PERRIN

City

Clermont-Ferrand

State/Province

Puy-de-Dôme

ZIP/Postal Code

63800

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Lucie BRUN, MD

lucie.brun@clermont.unicancer.fr

First Name & Middle Initial & Last Name & Degree

Julian BIAU, MD, PhD

julian.biau@clermont.unicancer.fr

First Name & Middle Initial & Last Name & Degree

Julian BIAU, MD, PhD

First Name & Middle Initial & Last Name & Degree

Lucie BRUN, MD

First Name & Middle Initial & Last Name & Degree

Juliette MOREAU, MD

First Name & Middle Initial & Last Name & Degree

Jessica MIROIR, MD

Facility Name

CHU Grenoble Alpes

City

Grenoble

ZIP/Postal Code

38700

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Andréa DESAGNEAUX, MD

First Name & Middle Initial & Last Name & Degree

Andréa DESAGNEAUX, MD

Facility Name

Hospices Civils de Lyon

City

Lyon

ZIP/Postal Code

69002

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Anne d'Hombres, MD

First Name & Middle Initial & Last Name & Degree

Anne d'Hombres, MD

Facility Name

Centre Léon BÉRARD

City

Lyon

ZIP/Postal Code

69373

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Coralie MONCHARMONT, MD

First Name & Middle Initial & Last Name & Degree

Coralie MONCHARMONT, MD

Facility Name

Centre Hospitalier d'Annecy-Genevois

City

Metz-Tessy

ZIP/Postal Code

74370

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Alexandre TESSIER, MD

First Name & Middle Initial & Last Name & Degree

Alexandre TESSIER, MD

Facility Name

Institut de Cancérologie de l'Ouest

City

Saint-Herblain

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

François THYLLAYS, MD

First Name & Middle Initial & Last Name & Degree

François THYLLAIS, MD

Facility Name

Institut de cancérologie de la Loire Lucien Neuwirth

City

Saint-Priest-en-Jarez

ZIP/Postal Code

42270

Country

France

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nicolas MAGNÉ, Pr

First Name & Middle Initial & Last Name & Degree

Nicolas MAGNÉ, Pr

Facility Name

Institut de cancérologie Strasbourg Europe (ICANS)

City

Strasbourg

ZIP/Postal Code

67000

Country

France

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Clara LEFEVRE, MD

First Name & Middle Initial & Last Name & Degree

Clara LEFEVRE, MD

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34320940

Citation

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.

Results Reference

background

Links:

URL

https://pubmed.ncbi.nlm.nih.gov/34320940/

Description

Study protocol article

Learn more about this trial

Preoperative Stereotactic Radiosurgery for Brain Metastases

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