HA-WBRT vs SRS in Patients With Multiple Brain Metastases

Phase 3

• Conditions: Brain Metastases
• Interventions: Radiation: Hippocampal Avoiding Whole Brain Radiation Therapy with Simultaneous Integrated Boost; Radiation: Single session or hypofractionated stereotactic radiosurgery

• Registration Number: NCT04277403
• Lead Sponsor: Medical University Innsbruck

Brief Summary

This study compares the effectiveness and safety of two radiation treatment techniques for patients with multiple brain metastases.

Detailed Description

For patients suffering from multiple brain metastases whole brain radiation therapy still constitutes a standard therapy. However, because of the risk of neurocognitive side effects as well as reduced local tumor control, employment of stereotactic radiosurgery (SRS) is becoming more common. The disadvantage of SRS alone may be poor intracranial tumor control because of frequent appearance of new distant brain metastases after therapy. In recent years hippocampal avoidance whole brain therapy has been shown to minimize treatment related side effects while reducing the rate of distant intracranial failure.

In this study patients will be randomized to receive either hippocampal avoidance whole brain radiation therapy with integrated tumor boost (HA-WBRT+SIB) or stereotactic radiosurgery. The investigators hypothesize that HA-WBRT+SIB can improve intracranial tumor control compared to stereotactic radiosurgery, while avoiding additional neurocognitive side effects.

Study Timeline

• Study First Submitted: 2020-02-06
• Study Start: 2020-02-15
• Study First Submitted QC: 2020-02-17
• Study First Posted: 2020-02-20
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-02
• Last Update Posted: 2021-09-05
• Primary Completion: 2023-02
• Study Completion: 2023-02

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• At least 4 and not exceeding 15 brain metastases not exceeding a combined total volume of 25ml and not previously treated with radiotherapy
• KPI ≥ 70, ECOG ≤ 2
• Age ≥ 18 years, Male or female

Exclusion Criteria

• Neuroendocrine, SCLC, germinoma or lymphoma histology
• Brain stem metastasis
• Life expectancy < 3 months
• Suspicion of meningeosis carcinomatosa
• Previous WBRT
• Inability to participate in radiologic follow-up, contraindication to MR imaging (e.g. not MRI compatible pacemaker, severe claustrophobia)
• Inability to participate in neurocognitive function testing, insufficient German language skills, aphasia, graphomotor impairment, insufficient vision, insufficient attention span
• Pregnancy, nursing or unwillingness to prevent pregnancy using effective methods of contraception during treatment
• Known abuse of medication, drugs or alcohol
• Known severe dementia (z-score < 2) or major cognitive function disorder that is not caused by intracranial tumour
• Known clinical depression or psychotic disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HA-WBRT+SIB	Hippocampal Avoiding Whole Brain Radiation Therapy with Simultaneous Integrated Boost	Hippocampal avoiding Whole brain radiation therapy (HA-WBRT) with volumetric modulated arc therapy (VMAT) with a simultaneously integrated boost (SIB) to each brain metastasis
SRS	Single session or hypofractionated stereotactic radiosurgery	Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases

Primary Outcome Measures

Name	Time	Method
Intracranial Progression free survival	up to 18 months	survival with freedom from both local and distant intracranial progression, measured in months from end of treatment until progression or death, assessed in follow-up imaging (MRI, FET-PET)

Secondary Outcome Measures

Name	Time	Method
Neurocognitive function assessed by TMT	up to 18 months	Change of z-scores of TMT (trail making test) to baseline examination
Quality of Life Score assessed by EORTC QLQ-C30 questionnaire	up to 18 months	Change in Quality of Life Score of EORTC QLQ-C30 (Quality of life core module) relative to baseline
Neurocognitive function assessed by VLMT	up to 18 months	Change of z-scores of VLMT (Verbaler Lern- und Merkfähigkeitstest) to baseline examination
Neurocognitive function assessed by COWAT	up to 18 months	Change of z-scores of COWAT (controlled oral word association test) to baseline examination
Local control rate	up to 18 months	rate of progression of treated metastases assessed in follow-up imaging (MRI, FET-PET)
Survival time	up to 18 months	time from end of treatment to death
Quality of Life Score assessed by QLQ-BN20 questionnaire	up to 18 months	Change in Quality of Life Score of QLQ-BN20 (quality of life brain cancer module) relative to baseline

Trial Locations

Locations (1)

Medical University Innsbruck; 🇦🇹 Innsbruck, Austria