Brain MicrometastasesNCT02220127
RCT of the 4mm vs. the 8mm Collimator for GKR of Brain Micrometastases
A study testing GKR with a single shot of the 8 mm collimator and GKR with a single shot of the 4 mm collimator in people with Brain Micrometastases, run by University College, London at 3 sites in United Kingdom.
Trial summary
Gamma Knife Radiosurgery (GKR) is a well-established treatment modality for brain metastasis (Chiou 2013; Salvetti, Nagaraja et al. 2013). Large multicentre series have been published on patients with single and multiple cerebral metastases, treated with GKR over a period of 30 years (Karlsson, Hanssens et al. 2009). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Micrometastases
- What is being tested?
- GKR with a single shot of the 8 mm collimator and GKR with a single shot of the 4 mm collimator
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 298 participants
- Where
- 3 sitesUnited Kingdom
- Study dates
- Sep 2014to Apr 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients with brain metastasis from any primary tumour receiving GKR.
- All intracranial micro-metastases including lesions located in the cerebral hemispheres, thalamus, basal ganglia and cerebellum and excluding lesions located in the brain stem below the level of the superior colliculi.
- Target volume < 0.14 cc3 and maximum diameter < 7 mm.
- The subject consents to participate in the study.
Who cannot join
- Inability to consent
- Younger than 18 years of age.
- Lesions in the brainstem (below the level of the superior colliculi) are better treated with the 4 mm collimator and they will be excluded from the study.
- Patients with more than 25 brain lesions suitable for randomisation will be excluded from the study.
- Co-morbidity or previous treatment such as surgery, chemotherapy or WBRT is not to be considered as exclusion criteria.
- Pregnancy in the context of brain metastases is not a contraindication for GKR, and therefore it will not be considered as exclusion criteria for this trial.
Trial locations and contacts
3 sites in 1 country.
United Kingdom3 sites, 3 recruiting
- Not yet recruiting
Gamma Knife Centre at BUPA Cromwell Hospital
London, SW5 0TU
Bodo Lippitz, MD, 020 7460 5938, bodo.lippitz@cromwellhospital.com
Bodo Lippitz, MD
- Recruiting
The Gamma Knife Centre at Queen Square
London, WC1N 3BG
Alvaro Villabona, Dr, +44 020 3448 4076, a.villabona.11@ucl.ac.uk
Ian Paddick, MSc,MIPM
- Not yet recruiting
BMI Thornbury Hospital
Sheffield, S10 3BR
Andras Kemeny, FRCS, MD, 01142674651, aakemeny@gmail.com
Andras Kemeny, FRCS, MD
About this study
Official title: Optimal Radiation Method for Gamma Knife Radiosurgery of Brain Micrometastases: A Multi-centre Randomised Clinical Trial (RCT) of the 4mm vs. the 8mm Collimator.
Gamma Knife Radiosurgery (GKR) is a well-established treatment modality for brain metastasis (Chiou 2013; Salvetti, Nagaraja et al. 2013). Large multicentre series have been published on patients with single and multiple cerebral metastases, treated with GKR over a period of 30 years (Karlsson, Hanssens et al. 2009). Multiple institutions have reported a consistently high local tumour control rate of 80%-90% following GKR (Chang, Lee et al. 2000; Da Silva, Nagayama et al. 2009; Salvetti, Nagaraja et al. 2013).
There is controversy over the use of GKR and/or Whole Brain Radiotherapy (WBRT) in patients with multiple metastases. WBRT provides a lower rate of distant recurrences, whereas GKR achieves good local control of treated lesions without the deleterious side effects of radiotherapy (Lippitz, Lindquist et al. 2014). This discussion is mainly focused on the risk of distant recurrences, which is lower if WBRT is given. There is evidence showing that Radiosurgery (RS) based on high contrast/resolution stereotactic MRI decreases the incidence and lengthens the time to distant recurrences (Hanssens, Karlsson et al. 2011). As a result, the current tendency is to treat all the lesions visible in high contrast/resolution images the day of Gamma Knife; which is followed by regular MRI follow ups and subsequent GKR for distant recurrences in order to avoid/delay WBRT.
It has been estimated that more than a half of distant recurrences will grow from tumour cells that were already in the brain (as micrometastases) when radiosurgery is delivered, but not much has been studied on the optimal prescription and radiation delivery method for these lesions. There is controversy over which collimator should be used when treating micro-metastases (BmM). These lesions can either be treated with the 4mm collimator at an isodose between the 40% and 90%, or the 8mm collimator at an isodose above 90%. The 8 mm collimator is thought to offer better Local Control Rate (LCR) with the advantage of faster delivered treatments, while the 4 mm collimator is considered to be safer, given its steep dose fall-off. It is the aim of this study to find out which of the 4 mm or 8 mm collimators can achieve the higher LCR with less complications. A large number of lesions will be randomised to either the 4 or the 8 mm collimator and the patients followed up to evaluate clinical efficacy.
- Conditions
- Brain Micrometastases
- Being tested
- GKR with a single shot of the 8 mm collimator, GKR with a single shot of the 4 mm collimator
- Keywords
- Brain, Neoplasm Micrometastasis, Gamma Knife Radiosurgery
- Medical subject headings
- Neoplasm Micrometastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GKR with a single shot of the 8 mm collimatorRadiation
Gamma Knife Radiosurgery (GKR) with a single shot of the 8 mm collimator at an isodose above 90%.
GKR with a single shot of the 4 mm collimatorRadiation
Gamma Knife Radiosurgery (GKR) with a single shot of the 4 mm collimator at an isodose between the 40% and 90%.
| Study group | Role | What they receive |
|---|---|---|
| 8 mm collimator | Experimental | GKR with a single shot of the 8 mm collimator Receives: Radiation: GKR with a single shot of the 8 mm collimator |
| 4 mm collimator | Experimental | GKR with a single shot of the 4 mm collimator Receives: Radiation: GKR with a single shot of the 4 mm collimator |
What is being measured
The primary outcome is the main question the study is designed to answer.
Local control rate (LCR)
LCR will be evaluated through volumetric assessment of the lesion the day of Gamma Knife and in subsequent follow up MRI scans
Measured: up to 24 months after treatment
Secondary outcomes (1)
Adverse radiation effects (ARE)
The following radiological and clinical outcomes will be used to assess ARE:
Bleeding from randomised lesions, Perilesional radiation induced necrosis, Severe peri-lesional oedema, New onset or worsened neurological deficit attributable to a randomised lesion
Measured: up to two years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2014 (estimated)
- Study startSep 2014
- Primary completionApr 2020 (estimated)
- Study completionApr 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MicrometastasesStudies of the same condition, open and under way.
- More trials run by University College, LondonThe 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
- Single blind
- Who is masked
- Participant
- Enrolment
- 298 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- University College London Hospitals
- Responsible party
- Sponsor
- Investigators
- Neil Kitchen, Mr, Study chair, National Hospital for Neurology and Neurosurgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02220127
- Sponsor's protocol ID
- 14/0050
- Other IDs
- 14/LO/0791, 145268
- Status last verified
- Mar 2015
- First submitted
- 18 Aug 2014
- Last updated
- 20 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Radiation Method for Gamma Knife Radiosurgery of Brain Micrometastases: A Multi-centre Randomised Clinical Trial (RCT) of the 4mm vs. the 8mm Collimator.
- ClinicalTrials.gov ID
- NCT02220127
- Acronym / sponsor ID
- 14/0050
- Conditions
- Brain Micrometastases
- Keywords
- Brain, Neoplasm Micrometastasis, Gamma Knife Radiosurgery
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 298 participants (estimated)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- University College London Hospitals
- Study start
- Sep 2014
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Apr 2021 (estimated)
- First posted
- 19 Aug 2014 (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.
Gamma Knife Radiosurgery (GKR) is a well-established treatment modality for brain metastasis (Chiou 2013; Salvetti, Nagaraja et al. 2013). Large multicentre series have been published on patients with single and multiple cerebral metastases, treated with GKR over a period of 30 years (Karlsson, Hanssens et al. 2009). Multiple institutions have reported a consistently high local tumour control rate of 80%-90% following GKR (Chang, Lee et al. 2000; Da Silva, Nagayama et al. 2009; Salvetti, Nagaraja et al. 2013).
There is controversy over the use of GKR and/or Whole Brain Radiotherapy (WBRT) in patients with multiple metastases. WBRT provides a lower rate of distant recurrences, whereas GKR achieves good local control of treated lesions without the deleterious side effects of radiotherapy (Lippitz, Lindquist et al. 2014). This discussion is mainly focused on the risk of distant recurrences, which is lower if WBRT is given. There is evidence showing that Radiosurgery (RS) based on high contrast/resolution stereotactic MRI decreases the incidence and lengthens the time to distant recurrences (Hanssens, Karlsson et al. 2011). As a result, the current tendency is to treat all the lesions visible in high contrast/resolution images the day of Gamma Knife; which is followed by regular MRI follow ups and subsequent GKR for distant recurrences in order to avoid/delay WBRT.
It has been estimated that more than a half of distant recurrences will grow from tumour cells that were already in the brain (as micrometastases) when radiosurgery is delivered, but not much has been studied on the optimal prescription and radiation delivery method for these lesions. There is controversy over which collimator should be used when treating micro-metastases (BmM). These lesions can either be treated with the 4mm collimator at an isodose between the 40% and 90%, or the 8mm collimator at an isodose above 90%. The 8 mm collimator is thought to offer better Local Control Rate (LCR) with the advantage of faster delivered treatments, while the 4 mm collimator is considered to be safer, given its steep dose fall-off. It is the aim of this study to find out which of the 4 mm or 8 mm collimators can achieve the higher LCR with less complications. A large number of lesions will be randomised to either the 4 or the 8 mm collimator and the patients followed up to evaluate clinical efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 8 mm collimator | Experimental | Radiation: GKR with a single shot of the 8 mm collimatorGKR with a single shot of the 8 mm collimator |
| 4 mm collimator | Experimental | Radiation: GKR with a single shot of the 4 mm collimatorGKR with a single shot of the 4 mm collimator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients with brain metastasis from any primary tumour receiving GKR.
- All intracranial micro-metastases including lesions located in the cerebral hemispheres, thalamus, basal ganglia and cerebellum and excluding lesions located in the brain stem below the level of the superior colliculi.
- Target volume < 0.14 cc3 and maximum diameter < 7 mm.
- The subject consents to participate in the study.
Key exclusion criteria (6 listed)
- Inability to consent
- Younger than 18 years of age.
- Lesions in the brainstem (below the level of the superior colliculi) are better treated with the 4 mm collimator and they will be excluded from the study.
- Patients with more than 25 brain lesions suitable for randomisation will be excluded from the study.
- Co-morbidity or previous treatment such as surgery, chemotherapy or WBRT is not to be considered as exclusion criteria.
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 |
|---|---|---|
| GKR with a single shot of the 8 mm collimatorGamma Knife Radiosurgery (GKR) with a single shot of the 8 mm collimator at an isodose above 90%. | Radiation | 8 mm collimator |
| GKR with a single shot of the 4 mm collimatorGamma Knife Radiosurgery (GKR) with a single shot of the 4 mm collimator at an isodose between the 40% and 90%. | Radiation | 4 mm collimator |
Primary outcome
Local control rate (LCR)
Time frame: up to 24 months after treatment
LCR will be evaluated through volumetric assessment of the lesion the day of Gamma Knife and in subsequent follow up MRI scans
1 secondary outcome
Adverse radiation effects (ARE)
Time frame: up to two years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2015.
- Related InfoLink provided by the sponsor.
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.
Neil Kitchen, Mr study chair
National Hospital for Neurology and Neurosurgery
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GKR with a single shot of the 8 mm collimator and GKR with a single shot of the 4 mm collimator in people with Brain Micrometastases, run by University College, London at 3 sites in United Kingdom.
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 20 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom. 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 Alvaro Villabona, Dr (+44 020 3448 4076, a.villabona.11@ucl.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Local control rate (LCR) (time frame: up to 24 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Mar 2015.