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

Primary Purpose

Brain Metastases, Adult

Status

Recruiting

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

preoperative radiosurgery

postoperative hypofractionated stereotactic radiotherapy

About this trial

This is an interventional treatment trial for Brain Metastases, Adult

Eligibility Criteria

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

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Age ≥18
Karnofsky performance status ≥60
Histological diagnosis of a malignant primary or metastatic tumour
Ability to take steroids
No contraindication to magnetic resonance imaging (MRI)
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
Survival estimated by primary clinician > 12 months
Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL

Exclusion Criteria:

Radiosensitive histology: germ cell tumour, lymphoma, multiple myeloma
>10 mm midline shift, effacement of the 4th ventricle or other sign of raised intracranial pressure requiring urgent decompressive surgery
More than 4 brain metastases or the diameter of the metastasis for resection >4.0 cm.
More than 1 metastasis requiring resection
Leptomeningeal disease in the CSF or on MRI (unless localized and can be irradiated then resected with the metastasis)
Prior radiation to the brain (SRS/SRT to lesion to be resected and /or WBRT)
Prior resection of a primary or secondary brain tumor
Prior diagnosis of a non-meningioma brain tumor
Prior radionuclide therapy within 30 days
Prior anti-VEGF therapy within 6 weeks
Unable to tolerate radiosurgery immobilization and treatment
Inability to give informed consent
Pregnancy or lactation
Females of reproductive potential not willing to use effective contraception for at least 6 months after radiotherapy
Males of reproductive potential not effective contraception for 3 months after radiotherapy
Lack of likely compliance with protocol and follow-up

Sites / Locations

Kantonsspital AarauRecruiting
Inselspital, Universitätsklinik für Radio-OnkologieRecruiting
Kantonsspital GraubündenRecruiting
Luzerner KantonsspitalRecruiting
Kantonsspital St. GallenRecruiting
Kantonsspital WinterthurRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Preoperative radiosurgery

Postoperative hypofractionated stereotactic radiotherapy

Arm Description

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

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.

Outcomes

Primary Outcome Measures

Leptomeningeal disease

Incidence (%)

Secondary Outcome Measures

Local control of the surgical cavity

No evidence of tumour recurrence on contrsat-enhanced MRI

Distant brain failure

New brain metastases

Radionecrosis

Adverse radiation effects

Quality of life assessment

EORTC questionnaire core questionnaire QLQ30, EORTC questionnaire brain module BN 20 (1-4, low scores reflect better QoL)

Full Information

NCT ID

NCT05124236

First Posted

October 14, 2021

Last Updated

September 7, 2022

Sponsor

Susanne Rogers

Collaborators

University of Basel, Technical University of Munich

1. Study Identification

Unique Protocol Identification Number

NCT05124236

Brief Title

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

Acronym

PREOP-2

Official Title

A Multicenter Prospective, Interventional, Randomized Trial of Preoperative Radiosurgery Compared With Postoperative Stereotactic Radiotherapy for Resectable Brain Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

September 2022

Overall Recruitment Status

Recruiting

Study Start Date

July 29, 2022 (Actual)

Primary Completion Date

December 30, 2025 (Anticipated)

Study Completion Date

December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Susanne Rogers

Collaborators

University of Basel, Technical University of Munich

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

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.

6. Conditions and Keywords

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

Brain Metastases, Adult

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Preoperative radiosurgery

Arm Type

Experimental

Arm Description

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

Arm Title

Postoperative hypofractionated stereotactic radiotherapy

Arm Type

Active Comparator

Arm Description

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.

Intervention Type

Radiation

Intervention Name(s)

preoperative radiosurgery

Intervention Description

single fraction radiosurgery

Intervention Type

Radiation

Intervention Name(s)

postoperative hypofractionated stereotactic radiotherapy

Intervention Description

5 fraction stereotactic radiotherapy /fractionated radiosurgery

Primary Outcome Measure Information:

Title

Leptomeningeal disease

Description

Incidence (%)

Time Frame

12 months after intervention

Secondary Outcome Measure Information:

Title

Local control of the surgical cavity

Description

No evidence of tumour recurrence on contrsat-enhanced MRI

Time Frame

12 months after intervention

Title

Distant brain failure

Description

New brain metastases

Time Frame

12 months after intervention

Title

Radionecrosis

Description

Adverse radiation effects

Time Frame

12 months after intervention

Title

Quality of life assessment

Description

EORTC questionnaire core questionnaire QLQ30, EORTC questionnaire brain module BN 20 (1-4, low scores reflect better QoL)

Time Frame

3,6,12 months after intervention

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Age ≥18 Karnofsky performance status ≥60 Histological diagnosis of a malignant primary or metastatic tumour Ability to take steroids No contraindication to magnetic resonance imaging (MRI) 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 Survival estimated by primary clinician > 12 months Platelet count > 100/ml, INR < 1.3, Hb > 7.5 g/dL Exclusion Criteria: Radiosensitive histology: germ cell tumour, lymphoma, multiple myeloma >10 mm midline shift, effacement of the 4th ventricle or other sign of raised intracranial pressure requiring urgent decompressive surgery More than 4 brain metastases or the diameter of the metastasis for resection >4.0 cm. More than 1 metastasis requiring resection Leptomeningeal disease in the CSF or on MRI (unless localized and can be irradiated then resected with the metastasis) Prior radiation to the brain (SRS/SRT to lesion to be resected and /or WBRT) Prior resection of a primary or secondary brain tumor Prior diagnosis of a non-meningioma brain tumor Prior radionuclide therapy within 30 days Prior anti-VEGF therapy within 6 weeks Unable to tolerate radiosurgery immobilization and treatment Inability to give informed consent Pregnancy or lactation Females of reproductive potential not willing to use effective contraception for at least 6 months after radiotherapy Males of reproductive potential not effective contraception for 3 months after radiotherapy Lack of likely compliance with protocol and follow-up

Central Contact Person:

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

Susanne Rogers, MD PhD

Phone

+41 62 838 5726

Susanne.rogers@ksa.ch

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

Oliver Riesterer, Prof.

Phone

+41 62 838 4249

oliver.riesterer@ksa.ch

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Susanne Rogers, MD PhD

Organizational Affiliation

Kantonsspital Aarau, Zentrum für Radio-Onkologie KSA-KSB

Official's Role

Principal Investigator

Facility Information:

Facility Name

Kantonsspital Aarau

City

Aarau

State/Province

Aargau

ZIP/Postal Code

5001

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Susanne J Rogers, MD PhD

Phone

0041628385726

susanne.rogers@ksa.ch

First Name & Middle Initial & Last Name & Degree

Sonja Schwenne

Phone

0041628386259

sonja.schwenne@ksa.ch

Facility Name

Inselspital, Universitätsklinik für Radio-Onkologie

City

Bern

State/Province

Freiburgstrasse

ZIP/Postal Code

3010

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ekin Ermis, Dr. med.

Phone

+41 31 632 26 32

erkin.ermis@insel.ch

Facility Name

Kantonsspital Graubünden

City

Chur

ZIP/Postal Code

7000

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Brigitta Baumert, Dr. med.

Phone

+41 81 256 64 90

rigitta.baumert@ksgr.ch

Facility Name

Luzerner Kantonsspital

City

Luzern

ZIP/Postal Code

6000

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gabriela Studer, Prof. Dr. med.

Phone

+41 205 58 01

gabriela.studer@luks.ch

Facility Name

Kantonsspital St. Gallen

City

St. Gallen

ZIP/Postal Code

9000

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Guido Henke, Dr. med.

Phone

+41 71 494 2192

guido.henke@kssg.ch

Facility Name

Kantonsspital Winterthur

City

Winterthur

ZIP/Postal Code

8400

Country

Switzerland

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Christoph Oehler, PD Dr. med.

Phone

+41 52 266 26 58

christoph.oehler@ksw.ch

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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