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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05124236
Recruitment Status : Recruiting
First Posted : November 17, 2021
Last Update Posted : September 10, 2022
Sponsor:
Collaborators:
University of Basel
Technical University of Munich
Information provided by (Responsible Party):
Susanne Rogers, Kantonsspital Aarau

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
Brain Metastases, Adult Radiation: preoperative radiosurgery Radiation: postoperative hypofractionated stereotactic radiotherapy Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : July 29, 2022
Estimated Primary Completion Date : December 30, 2025
Estimated Study Completion Date : December 30, 2025

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




Primary Outcome Measures :
  1. Leptomeningeal disease [ Time Frame: 12 months after intervention ]
    Incidence (%)


Secondary Outcome Measures :
  1. Local control of the surgical cavity [ Time Frame: 12 months after intervention ]
    No evidence of tumour recurrence on contrsat-enhanced MRI

  2. Distant brain failure [ Time Frame: 12 months after intervention ]
    New brain metastases

  3. Radionecrosis [ Time Frame: 12 months after intervention ]
    Adverse radiation effects

  4. Quality of life assessment [ Time Frame: 3,6,12 months after intervention ]
    EORTC questionnaire core questionnaire QLQ30, EORTC questionnaire brain module BN 20 (1-4, low scores reflect better QoL)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05124236


Contacts
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Contact: Susanne Rogers, MD PhD +41 62 838 5726 Susanne.rogers@ksa.ch
Contact: Oliver Riesterer, Prof. +41 62 838 4249 oliver.riesterer@ksa.ch

Locations
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Switzerland
Kantonsspital Aarau Recruiting
Aarau, Aargau, Switzerland, 5001
Contact: Susanne J Rogers, MD PhD    0041628385726    susanne.rogers@ksa.ch   
Contact: Sonja Schwenne    0041628386259    sonja.schwenne@ksa.ch   
Inselspital, Universitätsklinik für Radio-Onkologie Recruiting
Bern, Freiburgstrasse, Switzerland, 3010
Contact: Ekin Ermis, Dr. med.    +41 31 632 26 32    erkin.ermis@insel.ch   
Kantonsspital Graubünden Recruiting
Chur, Switzerland, 7000
Contact: Brigitta Baumert, Dr. med.    +41 81 256 64 90    rigitta.baumert@ksgr.ch   
Luzerner Kantonsspital Recruiting
Luzern, Switzerland, 6000
Contact: Gabriela Studer, Prof. Dr. med.    +41 205 58 01    gabriela.studer@luks.ch   
Kantonsspital St. Gallen Recruiting
St. Gallen, Switzerland, 9000
Contact: Guido Henke, Dr. med.    +41 71 494 2192    guido.henke@kssg.ch   
Kantonsspital Winterthur Recruiting
Winterthur, Switzerland, 8400
Contact: Christoph Oehler, PD Dr. med.    +41 52 266 26 58    christoph.oehler@ksw.ch   
Sponsors and Collaborators
Susanne Rogers
University of Basel
Technical University of Munich
Investigators
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Principal Investigator: Susanne Rogers, MD PhD Kantonsspital Aarau, Zentrum für Radio-Onkologie KSA-KSB
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Responsible Party: Susanne Rogers, Sponsor-Investigator, Kantonsspital Aarau
ClinicalTrials.gov Identifier: NCT05124236    
Other Study ID Numbers: 410.000.146
First Posted: November 17, 2021    Key Record Dates
Last Update Posted: September 10, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplastic Processes
Neoplasms
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases