HA-WBRT vs SRS in Patients With Multiple Brain Metastases (HipSter)

Hippocampal Avoidance Whole Brain Radiotherapy (HA-WBRT) and Stereotactic Radiosurgery (SRS) in Patients With Multiple Brain Metastases

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

Study Overview

• Status: Recruiting
• Conditions: Brain Metastases
• Intervention / Treatment: Radiation: Hippocampal Avoiding Whole Brain Radiation Therapy with Simultaneous Integrated Boost; Radiation: Single session or hypofractionated stereotactic radiosurgery

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 Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Julian Mangesius, MD; Email: julian.mangesius@i-med.ac.at

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Recruiting
    • Medical University Innsbruck
    • Contact: Julian Mangesius, MD; Email: julian.mangesius@i-med.ac.at
    • Principal Investigator: Ute Maria Ganswindt, MD, PhD
    • Sub-Investigator: Julian Mangesius, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HA-WBRT+SIB; Hippocampal avoiding Whole brain radiation therapy (HA-WBRT) with volumetric modulated arc therapy (VMAT) with a simultaneously integrated boost (SIB) to each brain metastasis	Radiation: 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 prescribed dose of 30Gy in 12 fractions, 2.5Gy per fraction and a simultaneously integrated boost (SIB) to each brain metastasis of 51Gy to 95% of PTV in 12 Fractions, 4.25Gy per fraction.
Active Comparator: SRS; Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases	Radiation: Single session or hypofractionated stereotactic radiosurgery; Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases. Single session SRS will be delivered in 18 to 22Gy to the tumour encompassing 80% Isodose. Hypofractionated stereotactic radiosurgery (HfSRS) will be delivered in 5 sessions of 6Gy each to the tumour encompassing 80% isodose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracranial Progression free survival	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)	up to 18 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Medical University Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2020
• Primary Completion (Anticipated): February 1, 2023
• Study Completion (Anticipated): February 1, 2023

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: February 17, 2020
• First Posted (Actual): February 20, 2020

Study Record Updates

• Last Update Posted (Actual): September 5, 2021
• Last Update Submitted That Met QC Criteria: September 2, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: radiosurgery; brain metastases; hippocampal avoidance
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: HIPSTER_2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No