Fractionated Stereotactic Radiotherapy vs. Single Session Radiosurgery in Patients With Larger Brain Metastases

Phase 3

Recruiting

• Conditions: Cerebral Metastases of Solid Cancers
• Interventions: Radiation: Radiosurgery; Radiation: Fractionated stereotactic radiotherapy

• Registration Number: NCT03697343
• Lead Sponsor: University of Erlangen-Nürnberg Medical School

Brief Summary

Phase III trial comparing local control and side effects after fractionated stereotactic radiotherapy and single session radiosurgery in patients with larger brain metastases (2-4 cm)

Detailed Description

This is a prospective, multicenter randomized trial comparing local control and side effects after fractionated stereotactic radiotherapy with 12 x 4 Gy and single session radiosurgery according to RTOG 9005 in patients with larger brain metastases (2-4 cm). Patients will be randomized to either fractionated stereotactic radiotherapy with 12 x 4 Gy or radiosurgery with 1 x 18 Gy (2-3 cm) or 1 x 15 Gy (3-4 cm) as defined by the RTOG 9005. Randomization will be stratified by metastasis volume and histology.

Study Timeline

• Study First Submitted: 2018-09-26
• Study First Submitted QC: 2018-10-04
• Study First Posted: 2018-10-05
• Study Start: 2021-05-18
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-09
• Last Update Posted: 2022-12-13
• Primary Completion: 2026-05
• Study Completion: 2026-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 382

Inclusion Criteria

• Age > 18 years, no upper age limit
• Karnofsky Performance Score > 50 points
• Expected Survival > 3 months
• 1-10 cerebral metastases of metastatic solid cancer
• Indication for local radiotherapy
• Patients must be able to understand the protocol and provide informed consent

Exclusion Criteria

• Whole Brain radiotherapy no longer than 6 weeks before the start of stereotactic radiotherapy or planned whole brain radiotherapy after stereotactic radiotherapy
• Prior irradiation of the cerebral metastasis that is to be treated in the study
• Relevant overlap of prior radiation fields with the metastasis that is to be treated in the study
• Metastasis in the brainstem
• Contraindication for cerebral MRI
• Metastasis that is to be treated in the study can't be visualized in contrast-enhanced T1 MRI sequence
• Pregnant or lactating women
• Abuse of illicit drugs, alcohol or medication
• Patient not able or willing to behave according to protocol
• Participation in another clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Radiosurgery with 1 x 18 Gy (2-3 cm) or 1 x 15 Gy (3-4 cm) and	Radiosurgery	Radiosurgery with 1 x 18 Gy (2-3 cm) or 1 x 15 Gy (3-4 cm) and no margin as defined by the RTOG 9005
Fractionated stereotactic radiotherapy with 12 x 4 Gy and 2 mm	Fractionated stereotactic radiotherapy	Fractionated stereotactic radiotherapy with 12 x 4 Gy and 2 mm margin

Primary Outcome Measures

Name	Time	Method
Time to local progression - TTLP	12 months	Local progression will be defined according to the RANO-BM criteria by an increase of at least 20% in the longest diameter of the metastasis relative to nadir or baseline. In addition to the relative increase of 20% the lesion must increase by an absolute value of 5 mm or more.; TTLP is defined as the time from randomization until the detection of progression as per the RANO-BM criteria. Patients will be censored if they have no signs of local progression at the time of last tumor monitoring during follow-up or at the onset of one of the following competing risk events not associated with local progression: death, lost to follow up, unauthorized non-protocol treatment of the target lesion.; Confirmatory analysis of the primary endpoint variable will be performed using a p-value of p≤0.05 as the global significance level.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	24 months	Overall Survival
Quality of Life according to EORTC QLQ-BN20	Change from baseline to 3, 6, 12 and 24 months	Quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ BN20
CNS toxicity according to CTCAE v5.0	12 months	CNS toxicity according to CTCAE v5.0
Time to local progression (Volumetric RANO-BM criteria)	12 months	Based on the RANO-BM criteria, progression is defined as an increase in volume of 72.8% or more (corresponds to a 20% increase in diameter for a perfect sphere).
Quality of Life according to EORTC QLQ-C30	Change from baseline to 3, 6, 12 and 24 months	Quality of life measured by European Organization for Research and Treatment of Cancer (EORTC) questionnaire QLQ C30
Local-Progression-Free Survival	12 months	Local-Progression-Free Survival is defined like TTLP except that death not associated with local progression will not be censored but assessed as a separate event

Trial Locations

Locations (13)

Klinik für Strahlentherapie und Radioonkologie Stuttgart; 🇩🇪 Stuttgart, Baden-Württemberg, Germany

Klinik für Strahlentherapie Bayreuth; 🇩🇪 Bayreuth, Bayern, Germany

Strahlentherapie Coburg; 🇩🇪 Coburg, Bayern, Germany

Radio-Log Strahlentherapie Hof; 🇩🇪 Hof, Bayern, Germany

Strahlentherapie Süd Kempten; 🇩🇪 Kempten, Bayern, Germany

Klinik und Poliklinik für Strahlentherapie Regensburg; 🇩🇪 Regensburg, Bayern, Germany

Klinik für Strahlentherapie und Radioonkologie; 🇩🇪 Bonn, Nordrhein-Westfalen, Germany

Universitätsklinik und Poliklinik für Strahlentherapie Halle; 🇩🇪 Halle, Sachsen-Anhalt, Germany

Klink und Praxis für Radioonkologie Chemnitz; 🇩🇪 Chemnitz, Sachsen, Germany

Klinik für Strahlentherapie und Radioonkologie Universitätsklinikum Jena; 🇩🇪 Jena, Thüringen, Germany

Klinik für Radioonkologie und Strahlentherapie Charité Berlin; 🇩🇪 Berlin, Germany

Erlangen, Universitätsklinikum Strahlenklinik; 🇩🇪 Erlangen, Germany

Klinik und Poliklinik für RadioOnkologie und Strahlentherapie München (TUM); 🇩🇪 München, Bayern, Germany