Brain MetastasesCYBER-SPACENCT03303365
Cyberknife Radiosurgery for Patients With Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence
A study testing stereotactic radiosurgery (SRS) in people with Brain Metastases and Adult Solid Tumor, run by Juergen Debus at 1 site in Germany.
Trial summary
For patients with cerebral oligometastases who are in adequate clinical condition stereotactic radiosurgery (SRS) is the treatment of choice, being recommended by international guidelines for the treatment of one to four lesions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Adult Solid Tumor
- What is being tested?
- stereotactic radiosurgery (SRS)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 203 participants
- Where
- 1 siteGermany
- Study dates
- 1 Feb 2018to 1 Jun 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
- radiologically confirmed metastases of the brain with an underlying history of a malignant illness
- between one and ten suspect intracranial lesions, taking into consideration all available series of the pre-therapeutic MRI (performed at Heidelberg University Hospital and including SPACE sequence)
- age ≥ 18 years of age
- Karnofsky Performance Score (KPS) ≥ 70
- for women with childbearing potential, (and men) adequate contraception.
- ability to understand character and individual consequences of the clinical trial
- written informed consent (must be available before enrolment in the trial)
Who cannot join
- refusal of the patient to take part in the study
- Small-cell lung cancer (SCLC) as primary malignant illness
- More than 10 suspect intracranial lesions in the initial pre-therapeutic MRI imaging (performed at Heidelberg University Hospital and including SPACE sequence)
- metastasis so close to OAR that initial single-session SRS would be impossible due to lacking radiotolerance
- known contraindications against the performing of cranial MRI
- previous radiotherapy of the brain
Show all 9Show fewer
- Patients who have not yet recovered from acute toxicities of prior therapies
- Pregnant or lactating women
- Participation in another clinical study or observation period of competing trials, respectively
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital of Heidelberg, Department of Radiation Oncology
Heidelberg, 69120
About this study
Official title: Cyberknife Radiosurgery for Patients With Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence - A Prospective Randomized Evaluation of Response and Toxicity
For patients with cerebral oligometastases who are in adequate clinical condition stereotactic radiosurgery (SRS) is the treatment of choice, being recommended by international guidelines for the treatment of one to four lesions. Newer findings have shown that for patients with more than four lesions SRS can be considered as a favorable alternative to whole-brain radiotherapy (WBRT), the currently established standard-of-care treatment. With modern techniques highly conformal SRS of multiple lesions has become feasible with comparable clinical effort and minimal toxicity as compared to WBRT. Developments in magnetic resonance imaging (MRI- imaging) have produced highly sensitive contrast-enhanced three-dimensional fast spin echo sequences such as SPACE that facilitate the detection of very small and early-stage lesions in a fashion superior to the established Magnetization Prepared Rapid Gradient Echo (MPRAGE) series.
Since it has been established that the response of brain metastases to SRS is better for smaller lesions and that WBRT can come at the price of significant neurotoxicity, the investigators hypothesize that 1) earlier detection of small brain metastases and 2) early and aggressive treatment of those by SRS will result in an overall clinical benefit by delaying the failure of repeated localized therapy and thus preserving quality of life and potentially prolonging overall survival. On the other hand however, overtreatment might be a valid concern with this approach since it has yet to be proved that a clinical benefit can be achieved.
The current study aims to stretch the boundaries of the term "cerebral oligometastases" by performing SRS for up to ten cerebral metastases, compared to the established clinical standard of four, given that existing data supports the non-inferiority of this approach and given that modern Cyberknife SRS facilitates the treatment of multiple lesions with minimal treatment-associated toxicity.
Read the detailed description
Scientific Background: Brain metastases are the most common intracranial cancer manifestations, affecting up to one third of adult cancer patients with systemic spread. Prognosis is generally poor with overall survival ranging below 6 months on average. However, a more detailed inspection reveals a prognostic subgroup, for which improved overall survival and clinical symptom control can be achieved and that is most descriptively characterized by favorable clinical performance (KPI ≥ 70%) and extracranially controlled disease. Whereas for most patients with brain metastases whole-brain radiotherapy, steroids or best supportive care represent the palliation treatment of choice, the abovementioned subgroup is eligible to profit from a locally radical therapy concept and in those cases neurosurgical resection and stereotactic radiosurgery have both produced favorable results. In patients unsuitable for neurosurgical resection, single- or multifraction, SRS has several distinct advantages over WBRT, the most significant being short treatment time, less posttherapeutic neurocognitive impairment, better local tumor control and little to no hair loss. Furthermore, SRS can be repeated multiple times or performed before or after WBRT. Current clinical guidelines recommend SRS in cases of cerebral oligometastases, defined as one to four intracranial lesions with an extracranially controlled systemic disease status. However, recent data suggests that it may be a suitable treatment for patients with five to ten or even more than ten lesions, being non-inferior to the SRS of four or less lesions. There are several factors supporting this rationale: On the one hand technical improvements in the field of SRS have significantly facilitated the treatment of a higher number of target lesions with little to no increase in toxicity and comparable clinical effort. On the other hand, the ever improving sensitivity of medical imaging has caused an increase in the detection of oligometastatic constellations, enabling their treatment in an earlier stage. For a long time the contrast-based high-resolution cranial computer tomography (cCT) had been the gold standard of detecting cerebral metastases. This was significantly improved by the introduction of magnetic resonance imaging (MRI) with contrast-enhanced T1-weighted sequences. Sensitivity was further improved with the introduction of 3T MRI into clinical routine and the development of high-resolution three-dimensional gradient-echo sequences such as the contrast-based T1-weighted MPRAGE, featuring a slice thickness of 0.9 mm and multiplanar reconstruction, thus enabling the detection of very small sized lesions in the range of one to a few millimeters. However, the use of gradient-echo (GE) techniques to obtain three-dimensional high-spatial-resolution images comes at the cost of inferior contrast enhancement and higher susceptibility to artifacts than is the case with two-dimensional spin-echo (SE) techniques. Recent developments in MRI research have produced another sequence that might prove even superior to MPRAGE in the specific detection of very small and early brain metastases: Sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) is a three-dimensional fast SE sequence that combines high contrast enhancement superior to MPRAGE with a high spatial resolution and multiplanar reconstruction. Kato et al. have found this sequence to be significantly superior to MPRAGE in the detection of contrast enhanced parenchymal lesions, especially if those are < 5mm in size as is characteristic of small very-early-stage cerebral metastases.
Trial Objectives: It is the purpose of this study to evaluate treatment response and toxicity after SRS of up to ten simultaneous cerebral metastases, treating either all lesions visible in the highly sensitive SPACE MRI sequence or only those visible in the conventional contrast-based MPRAGE sequence. Treatment response is evaluated with respect to the ineligibility for further cerebral SRS at 12 months after initial SRS, defined by simultaneous new occurrence or progression of > 10 brain metastases (as a surrogate parameter for overall local control), furthermore overall survival and cognitive function and quality of life.
Patients´Selection: A total of n=200 patients will be enrolled into the trial (n=100 per treatment group). All patients fulfilling the inclusion and exclusion criteria will be informed about the study and included into the study if they declare informed consent. Registration for the study must be performed before the start of RT.
Trial Design: The trial will be performed as a single-center two-armed prospective randomized Phase II study. Patients will be randomized into an experimental arm and a control arm. All patients will receive pre-therapeutic MRI imaging as described in (Chapter 6) and imaging will be assessed by a radiologist. For patients in the experimental arm, all available MRI series, including SPACE will be taken into consideration for the definition of treatment target lesions. For patients in the control arm the assessing radiologist will be blinded with respect to the SPACE sequence and for the definition of treatment target lesions primarily contrast-based three-dimensional MPRAGE, complemented by all non-SPACE MRI sequences will be taken into consideration.
- Conditions
- Brain Metastases, Adult Solid Tumor
- Being tested
- stereotactic radiosurgery (SRS)
- Keywords
- Brain Metastases, WBRT (whole brain radiotherapy), SRS (stereotactic radiosurgery), CYBER-Knife
- Medical subject headings
- Brain Neoplasms, Snyder Robinson syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stereotactic radiosurgery (SRS)Radiation
All patients will receive a pre-treatment cranial MRI for diagnostic and treatment planning purposes.
In Arm A, the contrast-based T1-weighted SPACE sequence is utilized for GTV definition. In Arm B, the contrast-based T1-weighted three-dimensional MPRAGE sequence is utilized for GTV definition. In both cases the GTV consists of all contrasted tissue associated with the target lesion and all additional tissue judged by an experienced physician to be part of the suspect target lesion. To the GTV a PTV margin of 1 mm is added by isotropic expansion that can be slightly modified if deemed necessary by the treating physician (e.g. intersection with adjoining OAR).
Dose prescription to the PTV for target lesions will be as follows:
- 20 Gy to the 70%-isodose (lesions < 2 cm max. diameter)
- 18 Gy to the 70%-isodose (lesions 2 - 3 cm max. diameter)
- 6 x 5 Gy to the conformally surrounding isodose (lesions > 3 cm max. diameter)
| Study group | Role | What they receive |
|---|---|---|
| Treatment based on SPACE MRI sequence | Experimental | Cyberknife SRS of all suspect intracranial lesions visible in SPACE up to 10 simultaneous lesions Receives: Radiation: stereotactic radiosurgery (SRS) |
| Treatment based on MPRAGE | Active comparator | Cyberknife SRS of all suspect intracranial lesions visible in MPRAGE up to 10 simultaneous lesions Receives: Radiation: stereotactic radiosurgery (SRS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ineligibility for further cerebral SRS
simultaneous new occurrence or progression of > 10 brain metastases
Measured: 12 months after initial SRS
Secondary outcomes (3)
Overall survival (OS)
Time interval between the date of RT begin and the date of death or date of leaving the study e.g., lost to follow up) whatever occurs first.
Measured: 12 months after initial SRS
cognitive function
CANTAB Test (Cambridge Neuropsychological Test Automated Battery )
Measured: 6 months after initial SRS
quality of life
EORTC QLQ-C30 questionnaire to assess the QoL of cancer patients, clinical assessment
Measured: 6 months after initial SRS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2017
- Study start1 Feb 2018
- Primary completion1 Jun 2021
- Study completion1 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- 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
- 203 participants (actual)
Sponsor and investigators
- Lead sponsor
- Juergen Debus
- Sponsor type
- University, hospital or other
- Collaborators
- Heidelberg University
- Responsible party
- Sponsor-investigator, Juergen Debus, University Hospital Heidelberg
- Investigators
- Juergen Debus, Prof. Dr.Dr., Principal investigator, Head of department Radiation Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03303365
- Sponsor's protocol ID
- S-448/2017
- Acronym
- CYBER-SPACE
- Status last verified
- Nov 2022
- First submitted
- 2 Oct 2017
- Last updated
- 3 Nov 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. 1996 Jul;7(3):337-44.
PubMed 8823767Arvold ND, Lee EQ, Mehta MP, Margolin K, Alexander BM, Lin NU, Anders CK, Soffietti R, Camidge DR, Vogelbaum MA, Dunn IF, Wen PY. Updates in the management of brain metastases. Neuro Oncol. 2016 Aug;18(8):1043-65. doi: 10.1093/neuonc/now127.
PubMed 27382120Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51. doi: 10.1016/s0360-3016(96)00619-0.
PubMed 9128946Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):510-4. doi: 10.1016/j.ijrobp.2007.06.074. Epub 2007 Oct 10.
PubMed 17931798Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, Ammirati M, Cobbs CS, Gaspar LE, Loeffler JS, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Paleologos NA, Patchell RA, Ryken TC, Kalkanis SN. The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010 Jan;96(1):45-68. doi: 10.1007/s11060-009-0073-4. Epub 2009 Dec 4.
PubMed 19960227Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10.
PubMed 24621620Wowra B, Muacevic A, Tonn JC. CyberKnife radiosurgery for brain metastases. Prog Neurol Surg. 2012;25:201-9. doi: 10.1159/000331193. Epub 2012 Jan 6.
PubMed 22236681Mugler JP 3rd, Bao S, Mulkern RV, Guttmann CR, Robertson RL, Jolesz FA, Brookeman JR. Optimized single-slab three-dimensional spin-echo MR imaging of the brain. Radiology. 2000 Sep;216(3):891-9. doi: 10.1148/radiology.216.3.r00au46891.
PubMed 10966728Kato Y, Higano S, Tamura H, Mugikura S, Umetsu A, Murata T, Takahashi S. Usefulness of contrast-enhanced T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions in detection of small brain metastasis at 3T MR imaging: comparison with magnetization-prepared rapid acquisition of gradient echo imaging. AJNR Am J Neuroradiol. 2009 May;30(5):923-9. doi: 10.3174/ajnr.A1506. Epub 2009 Feb 12.
PubMed 19213825Mulkern RV, Wong ST, Winalski C, Jolesz FA. Contrast manipulation and artifact assessment of 2D and 3D RARE sequences. Magn Reson Imaging. 1990;8(5):557-66. doi: 10.1016/0730-725x(90)90132-l.
PubMed 2082125Kakeda S, Korogi Y, Hiai Y, Ohnari N, Moriya J, Kamada K, Hanamiya M, Sato T, Kitajima M. Detection of brain metastasis at 3T: comparison among SE, IR-FSE and 3D-GRE sequences. Eur Radiol. 2007 Sep;17(9):2345-51. doi: 10.1007/s00330-007-0599-9. Epub 2007 Feb 22.
PubMed 17318603Chang EL, Hassenbusch SJ 3rd, Shiu AS, Lang FF, Allen PK, Sawaya R, Maor MH. The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases. Neurosurgery. 2003 Aug;53(2):272-80; discussion 280-1. doi: 10.1227/01.neu.0000073546.61154.9a.
PubMed 12925241Aoyama H, Tago M, Kato N, Toyoda T, Kenjyo M, Hirota S, Shioura H, Inomata T, Kunieda E, Hayakawa K, Nakagawa K, Kobashi G, Shirato H. Neurocognitive function of patients with brain metastasis who received either whole brain radiotherapy plus stereotactic radiosurgery or radiosurgery alone. Int J Radiat Oncol Biol Phys. 2007 Aug 1;68(5):1388-95. doi: 10.1016/j.ijrobp.2007.03.048.
PubMed 17674975Chang SD, Main W, Martin DP, Gibbs IC, Heilbrun MP. An analysis of the accuracy of the CyberKnife: a robotic frameless stereotactic radiosurgical system. Neurosurgery. 2003 Jan;52(1):140-6; discussion 146-7. doi: 10.1097/00006123-200301000-00018.
PubMed 12493111Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys. 1991 May 15;21(1):109-22. doi: 10.1016/0360-3016(91)90171-y.
PubMed 2032882
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cyberknife Radiosurgery for Patients With Brain Metastases Diagnosed With Either SPACE or MPRAGE Sequence - A Prospective Randomized Evaluation of Response and Toxicity
- ClinicalTrials.gov ID
- NCT03303365
- Acronym / sponsor ID
- CYBER-SPACE / S-448/2017
- Conditions
- Brain Metastases, Adult Solid Tumor
- Keywords
- Brain Metastases, WBRT (whole brain radiotherapy), SRS (stereotactic radiosurgery), CYBER-Knife
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 203 participants (actual)
- Lead sponsor
- Juergen DebusUniversity, hospital or other
- Collaborators
- Heidelberg University
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jun 2021 (actual)
- First posted
- 6 Oct 2017 (actual)
- 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.
For patients with cerebral oligometastases who are in adequate clinical condition stereotactic radiosurgery (SRS) is the treatment of choice, being recommended by international guidelines for the treatment of one to four lesions. Newer findings have shown that for patients with more than four lesions SRS can be considered as a favorable alternative to whole-brain radiotherapy (WBRT), the currently established standard-of-care treatment. With modern techniques highly conformal SRS of multiple lesions has become feasible with comparable clinical effort and minimal toxicity as compared to WBRT. Developments in magnetic resonance imaging (MRI- imaging) have produced highly sensitive contrast-enhanced three-dimensional fast spin echo sequences such as SPACE that facilitate the detection of very small and early-stage lesions in a fashion superior to the established Magnetization Prepared Rapid Gradient Echo (MPRAGE) series.
Since it has been established that the response of brain metastases to SRS is better for smaller lesions and that WBRT can come at the price of significant neurotoxicity, the investigators hypothesize that 1) earlier detection of small brain metastases and 2) early and aggressive treatment of those by SRS will result in an overall clinical benefit by delaying the failure of repeated localized therapy and thus preserving quality of life and potentially prolonging overall survival. On the other hand however, overtreatment might be a valid concern with this approach since it has yet to be proved that a clinical benefit can be achieved.
The current study aims to stretch the boundaries of the term "cerebral oligometastases" by performing SRS for up to ten cerebral metastases, compared to the established clinical standard of four, given that existing data supports the non-inferiority of this approach and given that modern Cyberknife SRS facilitates the treatment of multiple lesions with minimal treatment-associated toxicity.
Detailed description
Scientific Background: Brain metastases are the most common intracranial cancer manifestations, affecting up to one third of adult cancer patients with systemic spread. Prognosis is generally poor with overall survival ranging below 6 months on average. However, a more detailed inspection reveals a prognostic subgroup, for which improved overall survival and clinical symptom control can be achieved and that is most descriptively characterized by favorable clinical performance (KPI ≥ 70%) and extracranially controlled disease. Whereas for most patients with brain metastases whole-brain radiotherapy, steroids or best supportive care represent the palliation treatment of choice, the abovementioned subgroup is eligible to profit from a locally radical therapy concept and in those cases neurosurgical resection and stereotactic radiosurgery have both produced favorable results. In patients unsuitable for neurosurgical resection, single- or multifraction, SRS has several distinct advantages over WBRT, the most significant being short treatment time, less posttherapeutic neurocognitive impairment, better local tumor control and little to no hair loss. Furthermore, SRS can be repeated multiple times or performed before or after WBRT. Current clinical guidelines recommend SRS in cases of cerebral oligometastases, defined as one to four intracranial lesions with an extracranially controlled systemic disease status. However, recent data suggests that it may be a suitable treatment for patients with five to ten or even more than ten lesions, being non-inferior to the SRS of four or less lesions. There are several factors supporting this rationale: On the one hand technical improvements in the field of SRS have significantly facilitated the treatment of a higher number of target lesions with little to no increase in toxicity and comparable clinical effort. On the other hand, the ever improving sensitivity of medical imaging has caused an increase in the detection of oligometastatic constellations, enabling their treatment in an earlier stage. For a long time the contrast-based high-resolution cranial computer tomography (cCT) had been the gold standard of detecting cerebral metastases. This was significantly improved by the introduction of magnetic resonance imaging (MRI) with contrast-enhanced T1-weighted sequences. Sensitivity was further improved with the introduction of 3T MRI into clinical routine and the development of high-resolution three-dimensional gradient-echo sequences such as the contrast-based T1-weighted MPRAGE, featuring a slice thickness of 0.9 mm and multiplanar reconstruction, thus enabling the detection of very small sized lesions in the range of one to a few millimeters. However, the use of gradient-echo (GE) techniques to obtain three-dimensional high-spatial-resolution images comes at the cost of inferior contrast enhancement and higher susceptibility to artifacts than is the case with two-dimensional spin-echo (SE) techniques. Recent developments in MRI research have produced another sequence that might prove even superior to MPRAGE in the specific detection of very small and early brain metastases: Sampling perfection with application-optimized contrasts by using different flip angle evolutions (SPACE) is a three-dimensional fast SE sequence that combines high contrast enhancement superior to MPRAGE with a high spatial resolution and multiplanar reconstruction. Kato et al. have found this sequence to be significantly superior to MPRAGE in the detection of contrast enhanced parenchymal lesions, especially if those are < 5mm in size as is characteristic of small very-early-stage cerebral metastases.
Trial Objectives: It is the purpose of this study to evaluate treatment response and toxicity after SRS of up to ten simultaneous cerebral metastases, treating either all lesions visible in the highly sensitive SPACE MRI sequence or only those visible in the conventional contrast-based MPRAGE sequence. Treatment response is evaluated with respect to the ineligibility for further cerebral SRS at 12 months after initial SRS, defined by simultaneous new occurrence or progression of > 10 brain metastases (as a surrogate parameter for overall local control), furthermore overall survival and cognitive function and quality of life.
Patients´Selection: A total of n=200 patients will be enrolled into the trial (n=100 per treatment group). All patients fulfilling the inclusion and exclusion criteria will be informed about the study and included into the study if they declare informed consent. Registration for the study must be performed before the start of RT.
Trial Design: The trial will be performed as a single-center two-armed prospective randomized Phase II study. Patients will be randomized into an experimental arm and a control arm. All patients will receive pre-therapeutic MRI imaging as described in (Chapter 6) and imaging will be assessed by a radiologist. For patients in the experimental arm, all available MRI series, including SPACE will be taken into consideration for the definition of treatment target lesions. For patients in the control arm the assessing radiologist will be blinded with respect to the SPACE sequence and for the definition of treatment target lesions primarily contrast-based three-dimensional MPRAGE, complemented by all non-SPACE MRI sequences will be taken into consideration.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment based on SPACE MRI sequence | Experimental | Radiation: stereotactic radiosurgery (SRS)Cyberknife SRS of all suspect intracranial lesions visible in SPACE up to 10 simultaneous lesions |
| Treatment based on MPRAGE | Active comparator | Radiation: stereotactic radiosurgery (SRS)Cyberknife SRS of all suspect intracranial lesions visible in MPRAGE up to 10 simultaneous lesions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- radiologically confirmed metastases of the brain with an underlying history of a malignant illness
- between one and ten suspect intracranial lesions, taking into consideration all available series of the pre-therapeutic MRI (performed at Heidelberg University Hospital and including SPACE sequence)
- age ≥ 18 years of age
- Karnofsky Performance Score (KPS) ≥ 70
- for women with childbearing potential, (and men) adequate contraception.
Key exclusion criteria (9 listed)
- refusal of the patient to take part in the study
- Small-cell lung cancer (SCLC) as primary malignant illness
- More than 10 suspect intracranial lesions in the initial pre-therapeutic MRI imaging (performed at Heidelberg University Hospital and including SPACE sequence)
- metastasis so close to OAR that initial single-session SRS would be impossible due to lacking radiotolerance
- known contraindications against the performing of cranial MRI
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 |
|---|---|---|
| stereotactic radiosurgery (SRS)All patients will receive a pre-treatment cranial MRI for diagnostic and treatment planning purposes. In Arm A, the contrast-based T1-weighted SPACE sequence is utilized for GTV definition. In Arm B, the contrast-based T1-weighted three-dimensional MPRAGE sequence is utilized for GTV definition. In both cases the GTV consists of all contrasted tissue associated with the target lesion and all additional tissue judged by an experienced physician to be part of the suspect target lesion. To the GTV a PTV margin of 1 mm is added by isotropic expansion that can be slightly modified if deemed necessary by the treating physician (e.g. intersection with adjoining OAR). Dose prescription to the PTV for target lesions will be as follows: * 20 Gy to the 70%-isodose (lesions < 2 cm max. diameter) * 18 Gy to the 70%-isodose (lesions 2 - 3 cm max. diameter) * 6 x 5 Gy to the conformally surrounding isodose (lesions > 3 cm max. diameter) | Radiation | Treatment based on MPRAGE, Treatment based on SPACE MRI sequence |
Primary outcome
Ineligibility for further cerebral SRS
Time frame: 12 months after initial SRS
simultaneous new occurrence or progression of > 10 brain metastases
3 secondary outcomes
Overall survival (OS)
Time frame: 12 months after initial SRS
cognitive function
Time frame: 6 months after initial SRS
quality of life
Time frame: 6 months after initial SRS
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Background: PubMed 8823767Johnson JD, Young B. Demographics of brain metastasis. Neurosurg Clin N Am. 1996 Jul;7(3):337-44.
- Background: PubMed 27382120Arvold ND, Lee EQ, Mehta MP, Margolin K, Alexander BM, Lin NU, Anders CK, Soffietti R, Camidge DR, Vogelbaum MA, Dunn IF, Wen PY. Updates in the management of brain metastases. Neuro Oncol. 2016 Aug;18(8):1043-65. doi: 10.1093/neuonc/now127.
- Background: PubMed 9128946Gaspar L, Scott C, Rotman M, Asbell S, Phillips T, Wasserman T, McKenna WG, Byhardt R. Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials. Int J Radiat Oncol Biol Phys. 1997 Mar 1;37(4):745-51. doi: 10.1016/s0360-3016(96)00619-0.
- Background: PubMed 17931798Sperduto PW, Berkey B, Gaspar LE, Mehta M, Curran W. A new prognostic index and comparison to three other indices for patients with brain metastases: an analysis of 1,960 patients in the RTOG database. Int J Radiat Oncol Biol Phys. 2008 Feb 1;70(2):510-4. doi: 10.1016/j.ijrobp.2007.06.074. Epub 2007 Oct 10.
- Background: PubMed 19960227Linskey ME, Andrews DW, Asher AL, Burri SH, Kondziolka D, Robinson PD, Ammirati M, Cobbs CS, Gaspar LE, Loeffler JS, McDermott M, Mehta MP, Mikkelsen T, Olson JJ, Paleologos NA, Patchell RA, Ryken TC, Kalkanis SN. The role of stereotactic radiosurgery in the management of patients with newly diagnosed brain metastases: a systematic review and evidence-based clinical practice guideline. J Neurooncol. 2010 Jan;96(1):45-68. doi: 10.1007/s11060-009-0073-4. Epub 2009 Dec 4.
- Background: PubMed 24621620Yamamoto M, Serizawa T, Shuto T, Akabane A, Higuchi Y, Kawagishi J, Yamanaka K, Sato Y, Jokura H, Yomo S, Nagano O, Kenai H, Moriki A, Suzuki S, Kida Y, Iwai Y, Hayashi M, Onishi H, Gondo M, Sato M, Akimitsu T, Kubo K, Kikuchi Y, Shibasaki T, Goto T, Takanashi M, Mori Y, Takakura K, Saeki N, Kunieda E, Aoyama H, Momoshima S, Tsuchiya K. Stereotactic radiosurgery for patients with multiple brain metastases (JLGK0901): a multi-institutional prospective observational study. Lancet Oncol. 2014 Apr;15(4):387-95. doi: 10.1016/S1470-2045(14)70061-0. Epub 2014 Mar 10.
- Background: PubMed 22236681Wowra B, Muacevic A, Tonn JC. CyberKnife radiosurgery for brain metastases. Prog Neurol Surg. 2012;25:201-9. doi: 10.1159/000331193. Epub 2012 Jan 6.
- Background: PubMed 10966728Mugler JP 3rd, Bao S, Mulkern RV, Guttmann CR, Robertson RL, Jolesz FA, Brookeman JR. Optimized single-slab three-dimensional spin-echo MR imaging of the brain. Radiology. 2000 Sep;216(3):891-9. doi: 10.1148/radiology.216.3.r00au46891.
- Background: PubMed 19213825Kato Y, Higano S, Tamura H, Mugikura S, Umetsu A, Murata T, Takahashi S. Usefulness of contrast-enhanced T1-weighted sampling perfection with application-optimized contrasts by using different flip angle evolutions in detection of small brain metastasis at 3T MR imaging: comparison with magnetization-prepared rapid acquisition of gradient echo imaging. AJNR Am J Neuroradiol. 2009 May;30(5):923-9. doi: 10.3174/ajnr.A1506. Epub 2009 Feb 12.
- Background: PubMed 2082125Mulkern RV, Wong ST, Winalski C, Jolesz FA. Contrast manipulation and artifact assessment of 2D and 3D RARE sequences. Magn Reson Imaging. 1990;8(5):557-66. doi: 10.1016/0730-725x(90)90132-l.
- Background: PubMed 17318603Kakeda S, Korogi Y, Hiai Y, Ohnari N, Moriya J, Kamada K, Hanamiya M, Sato T, Kitajima M. Detection of brain metastasis at 3T: comparison among SE, IR-FSE and 3D-GRE sequences. Eur Radiol. 2007 Sep;17(9):2345-51. doi: 10.1007/s00330-007-0599-9. Epub 2007 Feb 22.
- Background: PubMed 12925241Chang EL, Hassenbusch SJ 3rd, Shiu AS, Lang FF, Allen PK, Sawaya R, Maor MH. The role of tumor size in the radiosurgical management of patients with ambiguous brain metastases. Neurosurgery. 2003 Aug;53(2):272-80; discussion 280-1. doi: 10.1227/01.neu.0000073546.61154.9a.
- Individual participant dataSharing planned: No
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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.
Juergen Debus, Prof. Dr.Dr. principal investigator
Head of department Radiation Oncology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing stereotactic radiosurgery (SRS) in people with Brain Metastases and Adult Solid Tumor, run by Juergen Debus at 1 site in Germany.
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 7 inclusion and 9 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: finished, as of the sponsor's last update on 3 Nov 2022. 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 Germany. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ineligibility for further cerebral SRS (time frame: 12 months after initial SRS). 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 NCT03303365, which also lists 21 linked publications.
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 3 Nov 2022.