Metastatic Malignant Neoplasm to the Adult BrainNCT01667640
Sector Irradiation Versus Whole Brain Irradiation for Brain Metastasis
A study testing sector irradiation and whole brain irradiation in people with Metastatic Malignant Neoplasm to the Adult Brain, run by Medical University Innsbruck at 1 site in Austria.
Trial summary
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients. To minimize the risk of intracranial recurrence whole brain irradiation has been established as standard adjuvant treatment in those patients. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Metastatic Malignant Neoplasm to the Adult Brain
- What is being tested?
- sector irradiation and whole brain irradiation
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteAustria
- Study dates
- Apr 2012to Apr 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Solitary/singular brain metastasis
- Karnofsky Performance Index > 60%
- Stable extracranial disease /CUP
- Informed consent
Who cannot join
- Small cell lung cancer
- Squamous cell lung cancer
- HER2-negative breast cancer
- Deep-seated location (e.g. basal ganglia)
- Expected surgery related neurological deficit
- Tumor diameter < 3cm
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Department of neurosurgery - Innsbruck
Innsbruck, Tyrol, 6020
Sabine Strauss, Mag, +43-512-504-27286
About this study
Official title: Sector Irradiation Versus Whole Brain Irradiation After Resection of Singular or Solitary Brain Metastasis - a Prospective Randomized Monocentric Trial
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients.
To minimize the risk of intracranial recurrence whole brain irradiation has been established as standard adjuvant treatment in those patients. Sector irradiation resembles a brain - tissue - sparing method by focusing the irradiation in the area of the tumor bed and a surrounding 1mm security margin.
The aim of this study is to investigate whether adjuvant "sector""-irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.
Read the detailed description
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients. Traditionally whole-brain irradiation is the treatment of choice following surgical resection. Whole brain irradiation has been the standard approach to minimize the risk of intracranial recurrence following resection of brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of resection of solitary metastases followed by whole brain irradiation compared with whole brain irradiation alone with regard to survival, local control, and length of functional independence. A following study by the same group failed to show a survival advantage for the addition of whole brain irradiation compared to surgical resection alone in patients with a solitary intracranial metastasis, although the likelihood of local and distant recurrence and death from neurological causes were significantly reduced by whole brain irradiation. Due to potential delayed neurocognitive effects associated with whole brain irradiation, investigators have evaluated the use of partial brain irradiation in the form of stereotactic radiosurgery instead of whole brain irradiation after resection of brain metastases. They showed that despite whole brain irradiation means superior control of brain recurrence in sites other than the resection bed, stereotactic radiosurgery after resection resulted in equivalent survival times and neurological preservation. In a retrospective series of 52 patients Karlovits et al. could show that stereotactic radiosurgery following surgical resection leads to equal local control compared to standard whole brain irradiation.
Study objective
The aim of this study is to investigate whether adjuvant "sector" -irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.
Hypothesis
- Sector irradiation is equal to whole-brain irradiation in local tumor control after 3, 6, 12 and 36 months and
- Sector irradiation" is superior to whole-brain irradiation in terms of quality of life and neurocognitive function
Patients and Methods
Patients with a single brain metastasis amenable to surgical resection fulfilling the inclusion criteria will be consecutively enrolled in this study. After microsurgical complete resection documented by early postoperative MRI within 72 hours and histological proven brain metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy and 6 and 12 months postoperatively. In case of local recurrence or developing further metastases a cross over to whole brain radiotherapy or focal irradiation is possible.
- Being tested
- sector irradiation, whole brain irradiation
- Keywords
- Brain metastases, radiation, sector, singular, solitary, neurocognition
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sector irradiationRadiation
Gross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin.
A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm.
Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules.
Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions.
Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported.
whole brain irradiationRadiation
For whole brain radiation the entire brain, the base of the skull and the meninges are included.
Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC.
The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented.
| Study group | Role | What they receive |
|---|---|---|
| whole brain irradiation | Active comparator | whole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges Receives: Radiation: whole brain irradiation |
| sector irradiation | Experimental | irradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions Receives: Radiation: sector irradiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
local tumor control
Measured: time from date of randomization until the date of first documented progression, assessed up to 36 months
Secondary outcomes (7)
distant brain metastasis
Measured: Time from date of randomization until the date of first documented progression elsewhere than the resection cavity, assessed at 3, 6, 12 and 36 months
time to clinical deterioration
Measured: Time from randomization to clinical deterioration, assessed by neurosurgeon in regular follow up visits at 3, 6, 12 and 36 months
local progression free survival
Measured: Time from randomization to the first documented tumor progressions in the resection cavity borders, assessed up to 36 months
quality of life
standardized assessment via "EORTC QLQ-C30/BN20" and the "FACT-Br" - questionary at 3, 6, 12 and 36 months after date of randomization
Measured: 3, 6, 12 and 36 months
neurocognitive functions
Neurocognitive testing by independent neuropsychologist at 3, 6, 12 and 36 months after date of randomization
Measured: 3, 6, 12 and 36 months postoperative
steroid dosage
Need of adjuvant steroid, assessed at 3, 6, 12 and 36 months after date of randomization
Measured: 3, 6, 12 and 36 months postoperative
overall survival
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2012 (estimated)
- Study startApr 2012
- Primary completionApr 2016 (estimated)
- Study completionApr 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Malignant Neoplasm to the Adult BrainStudies of the same condition, open and under way.
- More trials run by Medical University InnsbruckThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University Innsbruck
- Sponsor type
- University, hospital or other
- Collaborators
- Marcel Seiz-Rosenhagen MD, PD, Meinhard Nevinny-Stickel MD, Prof., Christian F Freyschlag MD, Günther Stockhammer MD, Prof., Bernhard Holzner MD, Doz, Johannes Giesinger Mag, Margarete Delazer MD, Prof., Thomas Bodner MD, MSc, Claudius Thomé MD, Prof.
- Responsible party
- Principal investigator, Kerschbaumer Johannes, Medical University Innsbruck
- Investigators
- Marcel Seiz-Rosenhagen, MD, PD, Principal investigator, Department of Neurosurgery, Medical University Innsbruck
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01667640
- Sponsor's protocol ID
- Sektorradv_4.0_04-2012
- Status last verified
- Apr 2015
- First submitted
- 7 Aug 2012
- Last updated
- 29 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kerschbaumer J, Pinggera D, Holzner B, Delazer M, Bodner T, Karner E, Dostal L, Kvitsaridze I, Minasch D, Thome C, Seiz-Rosenhagen M, Nevinny-Stickel M, Freyschlag CF. Sector Irradiation vs. Whole Brain Irradiation After Resection of Singular Brain Metastasis-A Prospective Randomized Monocentric Trial. Front Oncol. 2020 Nov 24;10:591884. doi: 10.3389/fonc.2020.591884. eCollection 2020.
PubMed 33330076
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sector Irradiation Versus Whole Brain Irradiation After Resection of Singular or Solitary Brain Metastasis - a Prospective Randomized Monocentric Trial
- ClinicalTrials.gov ID
- NCT01667640
- Acronym / sponsor ID
- Sektorradv_4.0_04-2012
- Keywords
- Brain metastases, radiation, sector, singular, solitary, neurocognition
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Medical University InnsbruckUniversity, hospital or other
- Collaborators
- Marcel Seiz-Rosenhagen MD, PD, Meinhard Nevinny-Stickel MD, Prof., Christian F Freyschlag MD, Günther Stockhammer MD, Prof., Bernhard Holzner MD, Doz, Johannes Giesinger Mag, Margarete Delazer MD, Prof., Thomas Bodner MD, MSc, Claudius Thomé MD, Prof.
- Study start
- Apr 2012
- Primary completion
- Apr 2016 (estimated)
- Study completion
- Apr 2017 (estimated)
- First posted
- 17 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients.
To minimize the risk of intracranial recurrence whole brain irradiation has been established as standard adjuvant treatment in those patients. Sector irradiation resembles a brain - tissue - sparing method by focusing the irradiation in the area of the tumor bed and a surrounding 1mm security margin.
The aim of this study is to investigate whether adjuvant "sector""-irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.
Detailed description
Microneurosurgical resection of intracerebral metastases leads to prolonged survival and relief of symptoms in selected patients. Traditionally whole-brain irradiation is the treatment of choice following surgical resection. Whole brain irradiation has been the standard approach to minimize the risk of intracranial recurrence following resection of brain metastases. Almost 2 decades ago, Patchell et al. established the superiority of resection of solitary metastases followed by whole brain irradiation compared with whole brain irradiation alone with regard to survival, local control, and length of functional independence. A following study by the same group failed to show a survival advantage for the addition of whole brain irradiation compared to surgical resection alone in patients with a solitary intracranial metastasis, although the likelihood of local and distant recurrence and death from neurological causes were significantly reduced by whole brain irradiation. Due to potential delayed neurocognitive effects associated with whole brain irradiation, investigators have evaluated the use of partial brain irradiation in the form of stereotactic radiosurgery instead of whole brain irradiation after resection of brain metastases. They showed that despite whole brain irradiation means superior control of brain recurrence in sites other than the resection bed, stereotactic radiosurgery after resection resulted in equivalent survival times and neurological preservation. In a retrospective series of 52 patients Karlovits et al. could show that stereotactic radiosurgery following surgical resection leads to equal local control compared to standard whole brain irradiation.
Study objective
The aim of this study is to investigate whether adjuvant "sector" -irradiation following microsurgical resection is equal to adjuvant whole brain irradiation in terms of local control and superior to in terms of quality of life and neurocognitive deficits in a prospective randomized trial.
Hypothesis
- Sector irradiation is equal to whole-brain irradiation in local tumor control after 3, 6, 12 and 36 months and
- Sector irradiation" is superior to whole-brain irradiation in terms of quality of life and neurocognitive function
Patients and Methods
Patients with a single brain metastasis amenable to surgical resection fulfilling the inclusion criteria will be consecutively enrolled in this study. After microsurgical complete resection documented by early postoperative MRI within 72 hours and histological proven brain metastasis patients will be randomized in arm A or B. Radiotherapy will start after 14th postoperative day within 3 weeks postoperatively. Study arm A means postoperative sector irradiation (30Gy), study arm B includes standard whole brain radiotherapy (40Gy). Follow up MRI will be every 3 months. Neurocognitive evaluation will be performed before radiotherapy and 6 and 12 months postoperatively. In case of local recurrence or developing further metastases a cross over to whole brain radiotherapy or focal irradiation is possible.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| whole brain irradiation | Active comparator | Radiation: whole brain irradiationwhole brain irradiation with 40 Gy, with fixation mask, radiation of the entire brain, skull base and meninges |
| sector irradiation | Experimental | Radiation: sector irradiationirradiation of the resection margin plus 5 mm safety margin with 30 Gy in 5 fractions |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Solitary/singular brain metastasis
- Karnofsky Performance Index > 60%
- Stable extracranial disease /CUP
- Informed consent
Key exclusion criteria (6 listed)
- Small cell lung cancer
- Squamous cell lung cancer
- HER2-negative breast cancer
- Deep-seated location (e.g. basal ganglia)
- Expected surgery related neurological deficit
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sector irradiationGross Tumor Volume (GTV) is defined as the visible margin of the resection on post- operative MRI and planning- CT-scan. The Clinical Treatment Volume (CTV) is the same as the GTV plus a 5 mm margin The Planning Treatment Volume (PTV) includes the CTV plus a 1mm margin. A non-invasive immobilization is used for the planning CT and treatment delivery with an accuracy of ≤ 1mm. Treatment planning will conform to ICRU 50/62 rules for coverage of GTV, CTV and PTV. Additionally, organs at risk are delineated according to the ICRU 62 rules. Treatment with radiotherapy will start 2 to 3 weeks after surgery. The prescribed dose for the PTV is 30 Gy in 5 fractions. Isodose distributions will be calculated through the target in three planes. Dose volume histograms will be reported. | Radiation | sector irradiation |
| whole brain irradiationFor whole brain radiation the entire brain, the base of the skull and the meninges are included. Radiation is performed fractionated with 40 Gy. The caudal boundary of the radiation-target volume is between the 2. and the 3. cervical vertebra. The radiation is performed via two lateral, opposing and isocentric contra fields. The face/ventral skull is shielded with individual blocs or MLC. The used energy for the radiation fields should be between 6 and 16 MV. The specification point of the dose or the standardization point has to be chosen in that way that the point is in the middle of the target volume. The target volume is radiated within the tolerance range of 95% - 107 %. The maximum/minimum doses in the target volume and possible doses peaks are documented. | Radiation | whole brain irradiation |
Primary outcome
local tumor control
Time frame: time from date of randomization until the date of first documented progression, assessed up to 36 months
7 secondary outcomes
distant brain metastasis
Time frame: Time from date of randomization until the date of first documented progression elsewhere than the resection cavity, assessed at 3, 6, 12 and 36 months
time to clinical deterioration
Time frame: Time from randomization to clinical deterioration, assessed by neurosurgeon in regular follow up visits at 3, 6, 12 and 36 months
local progression free survival
Time frame: Time from randomization to the first documented tumor progressions in the resection cavity borders, assessed up to 36 months
quality of life
Time frame: 3, 6, 12 and 36 months
neurocognitive functions
Time frame: 3, 6, 12 and 36 months postoperative
steroid dosage
Time frame: 3, 6, 12 and 36 months postoperative
overall survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2015.
- Derived from this study: PubMed 33330076Kerschbaumer J, Pinggera D, Holzner B, Delazer M, Bodner T, Karner E, Dostal L, Kvitsaridze I, Minasch D, Thome C, Seiz-Rosenhagen M, Nevinny-Stickel M, Freyschlag CF. Sector Irradiation vs. Whole Brain Irradiation After Resection of Singular Brain Metastasis-A Prospective Randomized Monocentric Trial. Front Oncol. 2020 Nov 24;10:591884. doi: 10.3389/fonc.2020.591884. eCollection 2020.
- Study center hompage.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marcel Seiz-Rosenhagen, MD, PD principal investigator
Department of Neurosurgery, Medical University Innsbruck
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing sector irradiation and whole brain irradiation in people with Metastatic Malignant Neoplasm to the Adult Brain, run by Medical University Innsbruck at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 29 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Johannes Kerschbaumer, MD (+43-512-504-82848, johannes.kerschbaumer@uki.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
local tumor control (time frame: time from date of randomization until the date of first documented progression, assessed up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01667640, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2015.