HA-WBRT vs SRS in Patients With Multiple Brain Metastases (HipSter)
Primary Purpose
Brain Metastases
Status
Unknown status
Phase
Phase 3
Locations
Austria
Study Type
Interventional
Intervention
Hippocampal Avoiding Whole Brain Radiation Therapy with Simultaneous Integrated Boost
Single session or hypofractionated stereotactic radiosurgery
Sponsored by
About this trial
This is an interventional treatment trial for Brain Metastases focused on measuring brain metastases, hippocampal avoidance, radiosurgery
Eligibility Criteria
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
Sites / Locations
- Medical University InnsbruckRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
HA-WBRT+SIB
SRS
Arm Description
Hippocampal avoiding Whole brain radiation therapy (HA-WBRT) with volumetric modulated arc therapy (VMAT) with a simultaneously integrated boost (SIB) to each brain metastasis
Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Neurocognitive function assessed by VLMT
Change of z-scores of VLMT (Verbaler Lern- und Merkfähigkeitstest) to baseline examination
Neurocognitive function assessed by COWAT
Change of z-scores of COWAT (controlled oral word association test) to baseline examination
Neurocognitive function assessed by TMT
Change of z-scores of TMT (trail making test) to baseline examination
Local control rate
rate of progression of treated metastases assessed in follow-up imaging (MRI, FET-PET)
Survival time
time from end of treatment to death
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
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
Full Information
NCT ID
NCT04277403
First Posted
February 6, 2020
Last Updated
September 2, 2021
Sponsor
Medical University Innsbruck
1. Study Identification
Unique Protocol Identification Number
NCT04277403
Brief Title
HA-WBRT vs SRS in Patients With Multiple Brain Metastases
Acronym
HipSter
Official Title
Hippocampal Avoidance Whole Brain Radiotherapy (HA-WBRT) and Stereotactic Radiosurgery (SRS) in Patients With Multiple Brain Metastases
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 15, 2020 (Actual)
Primary Completion Date
February 2023 (Anticipated)
Study Completion Date
February 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Medical University Innsbruck
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases
Keywords
brain metastases, hippocampal avoidance, radiosurgery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Care Provider
Masking Description
Observer-blinding
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
HA-WBRT+SIB
Arm Type
Experimental
Arm Description
Hippocampal avoiding Whole brain radiation therapy (HA-WBRT) with volumetric modulated arc therapy (VMAT) with a simultaneously integrated boost (SIB) to each brain metastasis
Arm Title
SRS
Arm Type
Active Comparator
Arm Description
Single session or hypofractionated stereotactic radiosurgery (SRS) of multiple brain metastases
Intervention Type
Radiation
Intervention Name(s)
Hippocampal Avoiding Whole Brain Radiation Therapy with Simultaneous Integrated Boost
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Single session or hypofractionated stereotactic radiosurgery
Intervention Description
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.
Primary Outcome Measure Information:
Title
Intracranial Progression free survival
Description
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)
Time Frame
up to 18 months
Secondary Outcome Measure Information:
Title
Neurocognitive function assessed by VLMT
Description
Change of z-scores of VLMT (Verbaler Lern- und Merkfähigkeitstest) to baseline examination
Time Frame
up to 18 months
Title
Neurocognitive function assessed by COWAT
Description
Change of z-scores of COWAT (controlled oral word association test) to baseline examination
Time Frame
up to 18 months
Title
Neurocognitive function assessed by TMT
Description
Change of z-scores of TMT (trail making test) to baseline examination
Time Frame
up to 18 months
Title
Local control rate
Description
rate of progression of treated metastases assessed in follow-up imaging (MRI, FET-PET)
Time Frame
up to 18 months
Title
Survival time
Description
time from end of treatment to death
Time Frame
up to 18 months
Title
Quality of Life Score assessed by EORTC QLQ-C30 questionnaire
Description
Change in Quality of Life Score of EORTC QLQ-C30 (Quality of life core module) relative to baseline
Time Frame
up to 18 months
Title
Quality of Life Score assessed by QLQ-BN20 questionnaire
Description
Change in Quality of Life Score of QLQ-BN20 (quality of life brain cancer module) relative to baseline
Time Frame
up to 18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julian Mangesius, MD
Email
julian.mangesius@i-med.ac.at
Facility Information:
Facility Name
Medical University Innsbruck
City
Innsbruck
ZIP/Postal Code
6020
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julian Mangesius, MD
Email
julian.mangesius@i-med.ac.at
First Name & Middle Initial & Last Name & Degree
Ute Maria Ganswindt, MD, PhD
First Name & Middle Initial & Last Name & Degree
Julian Mangesius, MD
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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HA-WBRT vs SRS in Patients With Multiple Brain Metastases
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