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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05124236
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

N/A
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Susanne Rogers
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Susanne Rogers, MD PhD
Principal Investigator Affiliation Kantonsspital Aarau, Zentrum für Radio-Onkologie KSA-KSB
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Switzerland
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Brain Metastases, Adult
Additional Details

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.

Arms & Interventions

Arms

Experimental: Preoperative radiosurgery

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

Active Comparator: 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.

Interventions

Radiation: - preoperative radiosurgery

single fraction radiosurgery

Radiation: - postoperative hypofractionated stereotactic radiotherapy

5 fraction stereotactic radiotherapy /fractionated radiosurgery

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Kantonsspital Aarau, Aarau, Aargau, Switzerland

Status

Recruiting

Address

Kantonsspital Aarau

Aarau, Aargau, 5001

Site Contact

Susanne J Rogers, MD PhD

[email protected]

0041628385726

Bern, Freiburgstrasse, Switzerland

Status

Recruiting

Address

Inselspital, Universitätsklinik für Radio-Onkologie

Bern, Freiburgstrasse, 3010

Site Contact

Ekin Ermis, Dr. med.

[email protected]

+41 31 632 26 32

Kantonsspital Graubünden, Chur, Switzerland

Status

Recruiting

Address

Kantonsspital Graubünden

Chur, , 7000

Site Contact

Brigitta Baumert, Dr. med.

[email protected]

+41 81 256 64 90

Luzerner Kantonsspital, Luzern, Switzerland

Status

Recruiting

Address

Luzerner Kantonsspital

Luzern, , 6000

Site Contact

Gabriela Studer, Prof. Dr. med.

[email protected]

+41 205 58 01

Kantonsspital St. Gallen, St. Gallen, Switzerland

Status

Recruiting

Address

Kantonsspital St. Gallen

St. Gallen, , 9000

Site Contact

Guido Henke, Dr. med.

[email protected]

+41 71 494 2192

Kantonsspital Winterthur, Winterthur, Switzerland

Status

Recruiting

Address

Kantonsspital Winterthur

Winterthur, , 8400

Site Contact

Christoph Oehler, PD Dr. med.

[email protected]

+41 52 266 26 58

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