Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

NCT ID: NCT05124236

Last Updated: 2024-11-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-29
• Study Completion Date: 2025-12-30

Brief Summary

The research question is whether a single fraction of preoperative radiosurgery can reduce the incidence of leptomeningeal disease 12 months following resection of a brain metastasis (BM) as compared with 5 fractions of postoperative stereotactic radiotherapy.

Detailed Description

Neurosurgical resection of a brain metastasis in patients with a diagnosis of cancer may be indicated however the recurrence rate approximates 50% and adjuvant radiotherapy is standard. Single fraction postoperative stereotactic radiosurgery (SRS) has been widely adopted as a standard therapy as it achieves equivalent survival and prevents loss of neurocognitive function as compared with whole brain radiotherapy and improves cavity local control rates as compared with observation. Hypofractionated stereotactic radiotherapy in 3 to 5 fractions (hfSRT) is also used in the postoperative setting.

Nodular leptomeningeal disease (nLMD) is a recognised pattern of failure after postoperative SRS and hfSRT. A 16.9% incidence of nodular LMD was seen after surgery and a similar incidence of 11%-28%is reported following postoperative SRS in retrospective series. These data suggest that postoperative SRS/hfSRT have no significant effect on the development of LMD following surgery.

The incidence of LMD following single fraction preoperative SRS is only 6.1% according to the largest retrospective series. Preoperative SRS takes advantage of the easier delineation of an intact BM and sterilizes tumor cells disseminated at surgery. Side effects are minimized by a smaller planning margin, a dose reduction and resection of the irradiated volume. In addition, there is no delay to systemic therapy due to wound healing/complications. Furthermore, a single fraction offers patient convenience.

This trial will randomise and compare intracranial outcomes between single fraction preoperative SRS and 5 fraction postoperative hFSRT.

Conditions

Brain Metastases, Adult

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Preoperative radiosurgery

The interventional arm is single fraction preoperative radiosurgery to a brain metastasis identified for neurosurgical resection.

Group Type: EXPERIMENTAL

preoperative radiosurgery

Intervention Type: RADIATION

single fraction radiosurgery

Postoperative hypofractionated stereotactic radiotherapy

The active comparator arm is the standard of care of postoperative hypofractionated stereotactic radiotherapy to the surgical cavity in 5 fractions following resection of the brain metastasis.

Group Type: ACTIVE_COMPARATOR

postoperative hypofractionated stereotactic radiotherapy

Intervention Type: RADIATION

5 fraction stereotactic radiotherapy /fractionated radiosurgery

Interventions

preoperative radiosurgery

single fraction radiosurgery

Intervention Type: RADIATION

postoperative hypofractionated stereotactic radiotherapy

5 fraction stereotactic radiotherapy /fractionated radiosurgery

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Age ≥18

4. Karnofsky performance status ≥60

5. Histological diagnosis of a malignant primary or metastatic tumour

6. Ability to take steroids

7. No contraindication to magnetic resonance imaging (MRI)

8. MRI-diagnosis of a clearly demarcated contrast-enhancing brain metastasis up to 4.0 cm diameter indicated for neurosurgical resection (tumorboard decision). Up to 3 other brain metastases suitable for primary radiosurgery/ stereotactic radiotherapy

9. Survival estimated by primary clinician > 12 months

10. Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL

Exclusion Criteria

1. Radiosensitive histology: germ cell tumour, lymphoma, multiple myeloma

2. >10 mm midline shift, effacement of the 4th ventricle or other sign of raised intracranial pressure requiring urgent decompressive surgery

3. More than 4 brain metastases or the diameter of the metastasis for resection >4.0 cm.

4. More than 1 metastasis requiring resection

5. Leptomeningeal disease in the CSF or on MRI (unless localized and can be irradiated then resected with the metastasis)

6. Prior radiation to the brain (SRS/SRT to lesion to be resected and /or WBRT)

7. Prior resection of a primary or secondary brain tumor

8. Prior diagnosis of a non-meningioma brain tumor

9. Prior radionuclide therapy within 30 days

10. Prior anti-VEGF therapy within 6 weeks

11. Unable to tolerate radiosurgery immobilization and treatment

12. Inability to give informed consent

13. Pregnancy or lactation

14. Females of reproductive potential not willing to use effective contraception for at least 6 months after radiotherapy

15. Males of reproductive potential not effective contraception for 3 months after radiotherapy

16. Lack of likely compliance with protocol and follow-up

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Basel

OTHER

Sponsor Role: collaborator

Susanne Rogers

OTHER

Sponsor Role: lead

Responsible Party

Susanne Rogers

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Susanne Rogers, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Kantonsspital Aarau, Radio-Onkologie-Zentrum Mittelland

Locations

Tirol Kliniken Innsbruck

Innsbruck, , Austria

Site Status: RECRUITING

Universitätsklinikum Schleswig Holstein

Kiel, , Germany

Site Status: RECRUITING

Kantonsspital Aarau

Aarau, Canton of Aargau, Switzerland

Site Status: RECRUITING

Inselspital, Universitätsklinik für Radio-Onkologie

Bern, Freiburgstrasse, Switzerland

Site Status: RECRUITING

Kantonsspital Graubünden

Chur, , Switzerland

Site Status: RECRUITING

Luzerner Kantonsspital

Lucerne, , Switzerland

Site Status: RECRUITING

Kantonsspital St. Gallen

Sankt Gallen, , Switzerland

Site Status: RECRUITING

Kantonsspital Winterthur

Winterthur, , Switzerland

Site Status: RECRUITING

Countries

Austria; Germany; Switzerland

Central Contacts

Susanne Rogers, MD PhD

Role: CONTACT

Susanne.rogers@ksa.ch

+41 62 838 57 26

Oliver Riesterer, Prof.

Role: CONTACT

oliver.riesterer@ksa.ch

+41 62 838 4249

Facility Contacts

Danijela Minasch, dr.

Role: primary

danijela.minasch@tirol-kliniken.at

0043 512 504 82782

Michael Synowitz, Prof. Dr. med.

Role: primary

Michael.Synowitz@uksh.de

0049 431-50023601

Oliver Blanck, Priv.-Doz. Dr.

Role: backup

oliver.blanck@uksh.de

+49 431 50026666

Susanne J Rogers, MD PhD

Role: primary

susanne.rogers@ksa.ch

0041628385726

Sonja Schwenne

Role: backup

sonja.schwenne@ksa.ch

0041628386259

Ekin Ermis, Dr. med.

Role: primary

erkin.ermis@insel.ch

+41 31 632 26 32

Brigitta Baumert, Dr. med.

Role: primary

rigitta.baumert@ksgr.ch

+41 81 256 64 90

Gabriela Studer, Prof. Dr. med.

Role: primary

gabriela.studer@luks.ch

+41 205 58 01

Guido Henke, Dr. med.

Role: primary

guido.henke@kssg.ch

+41 71 494 2192

Christoph Oehler, PD Dr. med.

Role: primary

christoph.oehler@ksw.ch

+41 52 266 26 58

Other Identifiers

410.000.146

Identifier Type: -

Identifier Source: org_study_id