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PREOP-2: Trial of Preoperative Radiosurgery Versus Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

Sponsor
Susanne Rogers (Other)
Overall Status
Recruiting
CT.gov ID
NCT05124236
Collaborator
University of Basel (Other), Technische Universität München (Other)
200
Enrollment
6
Locations
2
Arms
41.1
Anticipated Duration (Months)
33.3
Patients Per Site
0.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Radiation: preoperative radiosurgery
  • Radiation: postoperative hypofractionated stereotactic radiotherapy
 N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
200 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Prospective, Interventional, Randomized Trial of Preoperative Radiosurgery Compared With Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases
Actual Study Start Date :
Jul 29, 2022
Anticipated Primary Completion Date :
Dec 30, 2025
Anticipated Study Completion Date :
Dec 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Preoperative radiosurgery

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

Radiation: preoperative radiosurgery
single fraction radiosurgery
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.

Radiation: postoperative hypofractionated stereotactic radiotherapy
5 fraction stereotactic radiotherapy /fractionated radiosurgery

Outcome Measures

Primary Outcome Measures

  1. Leptomeningeal disease [12 months after intervention]

    Incidence (%)

Secondary Outcome Measures

  1. Local control of the surgical cavity [12 months after intervention]

    No evidence of tumour recurrence on contrsat-enhanced MRI

  2. Distant brain failure [12 months after intervention]

    New brain metastases

  3. Radionecrosis [12 months after intervention]

    Adverse radiation effects

  4. Quality of life assessment [3,6,12 months after intervention]

    EORTC questionnaire core questionnaire QLQ30 (1-4, low scores reflect better QoL)

  5. Quality of life assessment [3,6,12 months after intervention]

    EORTC questionnaire brain module BN 20 (1-4, low scores reflect better QoL)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Kantonsspital Aarau Aarau Aargau Switzerland 5001
2 Inselspital, Universitätsklinik für Radio-Onkologie Bern Freiburgstrasse Switzerland 3010
3 Kantonsspital Graubünden Chur Switzerland 7000
4 Luzerner Kantonsspital Luzern Switzerland 6000
5 Kantonsspital St. Gallen St. Gallen Switzerland 9000
6 Kantonsspital Winterthur Winterthur Switzerland 8400

Sponsors and Collaborators

  • Susanne Rogers
  • University of Basel
  • Technische Universität München

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Susanne Rogers, Sponsor-Investigator, Kantonsspital Aarau
ClinicalTrials.gov Identifier:
NCT05124236
Other Study ID Numbers:
  • 410.000.146
First Posted:
Nov 17, 2021
Last Update Posted:
Aug 1, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms

Study Results

No Results Posted as of Aug 1, 2022