Brain Metastases, AdultPhase 2ESTRONNCT03285932
Stereotactic Radiotherapy of the Resection Cavity of Brain Metastases vs. Post-operative Whole-brain Radiotherapy
A Phase 2 study testing post-operative stereotactic radiosurgery (SRS) and Whole brain radiotherapy (WBRT) in people with Brain Metastases, Adult, run by Juergen Debus at 1 site in Germany.
Trial summary
In advanced cancer disease brain metastases are common, difficult to treat, and are associated with a poor prognosis. As new local and systemic therapies are eventually resulting in improved survival and quality of life for patients with brain metastases, negative neurocognitive effects of radiation therapy are… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Adult
- What is being tested?
- post-operative stereotactic radiosurgery (SRS) and Whole brain radiotherapy (WBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 1 siteGermany
- Study dates
- 1 Feb 2018to 8 Jul 2021
- Phase
- Phase 2
- 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
- histologically confirmed solid cancer
- MRI confirmed cerebral metastases
- Neurosurgical resection of one cerebral metastasis
- age ≥ 18 years of age
- Karnofsky Performance Score >60
- 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 patients to take part in the study
- previous radiotherapy to the brain
- > 10 unresected brain metastases in postoperative MRI
- Patients who have not yet recovered from acute toxicities of prior therapies
- known carcinoma < 2 years ago (excluding carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
- pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Radiotherapy, University of Heidelberg
Heidelberg, 69120
About this study
Official title: Evaluation of Stereotactic Radiotherapy of the Resection Cavity After Surgery of Brain Metastases Compared to Post-operative Whole-brain Radiotherapy
In advanced cancer disease brain metastases are common, difficult to treat, and are associated with a poor prognosis. As new local and systemic therapies are eventually resulting in improved survival and quality of life for patients with brain metastases, negative neurocognitive effects of radiation therapy are becoming increasingly important as well as good loco-regional disease control of brain metastases.
Concerning treatment, brain metastases remain a major clinical problem and a multidisciplinary approach to management should be adopted. Neurosurgical resection with postoperative whole brain radiotherapy (WBRT) is one major treatment option in solitary or symptomatic brain metastases. Furthermore, WBRT is recommended for multiple brain metastases. For a limited number of brain metastases stereotactic radiosurgery (SRS) has been established as a highly effective treatment alternative.
Read more
Recently, a new treatment approach combing neurosurgery with postoperative stereotactic radiotherapy (SRT) of the resection cavity is emerging. Based on available evidence, postoperative SRT of the resection cavity improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated (1).
This protocol is aimed at primarily evaluating the safety and toxicity profile of SRT to the resection cavity following neurosurgical resection combined with SRT of potentially further unresected brain metastases, compared to postoperative whole-brain radiotherapy (WBRT). Secondary, the local effect of SRT in patients with brain metastases will be assessed by measuring time to local recurrence (LR), local and loco-regional progression-free survival (PFS).
Additional systemic treatment will be carried out according to the standards of the National Center for Tumor Therapy (NCT).
Read the detailed description
Scientific Background: Brain metastases (BM) represent a significant healthcare problem. It is estimated that 20% to 40% of patients with cancer will develop metastatic cancer to the brain during the course of their illness 1. The most common primary sites are lung, melanoma, renal, breast and colorectal cancer 2. Options for patients with brain metastases had been limited to whole brain radiotherapy (WBRT) or supportive care alone, and systemic chemotherapy was often discontinued. Historically, the best possible supportive care or whole-brain radiotherapy (WBRT) were the standard of care 1 aiming at temporary symptom relief. For WBRT, efficacy in symptom relief but also in prolongation of the median survival time by 3-6 months is well documented. To date, microsurgical approaches and SRS, both proved to be safe and efficient, offer alternative treatment options that potentially meet these concerns 6,7. After proving its efficacy in achieving local tumor control in the treated volume, SRS was used as a stand-alone treatment option in patients with oligometastases (one to four metastases) in the brain. There is a rapidly expanding recent body of literature on outcomes of single-fraction SRS or hypofractionated SRS targeting the resection cavity after surgical resection of BM. Several retrospective series assessed the efficacy and safety of postoperative SRS to the resection cavity 9 aiming at an enhanced local tumor control but also at avoidance of the neurotoxic late effects of WBRT. WBRT followed by SRS of the tumor bed leads to 1-year local control rates of 70-93 %, which is comparable to results after surgery followed by WBRT. Median survival was 12-18 months with a 1-year incidence of new metastases in the brain of 45-60 %.
Trial Objectives: This protocol is primarily aimed at evaluating the safety and toxicity profile of SRS following neurosurgical resection and compares it to that of WBRT as the established standard of care. Secondary, the local effect of radiation therapy in patients with brain metastases will be assessed by measuring time to local and loco-regional recurrence, local and loco-regional PFS and overall survival at 12 months after treatment.
Patients´Selection: Patients with the diagnosis of brain metastases from solid tumors that have undergone neurosurgical resection of one brain metastasis will be evaluated and screened for the protocol. 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 post-operative contrast-enhanced cranial MRI imaging and imaging will be assessed by a radiologist. All available MRI sequences, including SPACE will be taken into consideration for the definition of treatment target lesions. Patients for whom the post-operative MRI reveals more than 10 suspect intracranial lesions (all sequences taken into account) will not be included in the trial.
- Conditions
- Brain Metastases, Adult
- Being tested
- post-operative stereotactic radiosurgery (SRS), Whole brain radiotherapy (WBRT)
- Keywords
- Brain Metastase, Radiation of resection cavity, WBRT (whole brain radiotherapy), SRS (stereotactic radiosurgery)
- 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.
post-operative stereotactic radiosurgery (SRS)Radiation
For radiosurgery, patients will be immobilized. Treatment planning including the MRI and planning CT should be performed 1 -2 weeks before SRT and treatment finished at latest 3-4 weeks after surgery. Planning should be as close to SRT as possible.
Organs at risk such as the brain stem, optic nerves, chiasm and spinal cord will be contoured. The Clinical Target Volume 1 (CTV1) will be defined as the resection cavity based on MRI and CT including T1 contrast enhanced changes around the resection cavity. The Clinical Target Volume 2 (CTV2) will be defined as a 3mm margin added to CTV1 by isotropic expansion and slightly adjusted as deemed appropriated by the experienced contouring physician. The Planning Target Volume (PTV) will be an additional margin of 1mm added to CTV2 by isotropic expansion.
Treatment planning will be performed using Accuray's Multiplan or subsequent approved treatment planning systems for Cyberknife.
Whole brain radiotherapy (WBRT)Radiation
For WBRT, an individual head fixation mask is manufactured for each patient, and treatment planning is performed as virtual simulation or 3D-conformal RT planning based on CT-imaging. The portals include the whole brain with special focus as including the skull base areas and lamina cribrosa. For low infratentorial lesions, the treatment volume may include the whole brain down to the second cervical vertbra.
RT will be applied with two portals (e.g. 87°and 273°) using a 6 MeV linear accelerator.
For WBRT, a total dose of 30 Gy in 3 Gy fractions will be applied.
| Study group | Role | What they receive |
|---|---|---|
| Post-operative SRS of resection cavity | Experimental | High-resolution contrast-enhanced post-operative MRI imaging in preparation for Cyberknife SRS. Cyberknife SRS of the resection cavity and all potential additional metastases diagnosed in the treatment planning MRI (up to 10 lesions)
Resection cavity:
7 x 5 Gy @ 95%-isodose
Potential additional brain metastases:
20 Gy @ 70%-isodose (lesions < 2 cm max. diameter) 18 Gy @ 70%-isodose (lesions 2 - 3 cm max. diameter) 6 x 5 Gy @ 70%-isodose (lesions > 3 cm max. diameter) Receives: Radiation: post-operative stereotactic radiosurgery (SRS) |
| Post-operative WBRT | Other | Post-operative WBRT will be performed according to the following dose regimen: 10 x 3 Gy Receives: Radiation: Whole brain radiotherapy (WBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
neurological progression-free survival (PFS)
Neurologic progression-free survival in follow-up imaging is the primary endpoint of the study. The duration is defined as the time interval between the date start of RT and the date of local and loco-regional progression or death, or the date of leaving the study without local and loco-regional progression (e.g., lost to follow up non-local progression) whatever occurs first. Patients not reported local and loco-regional progressive or dead, or lost to follow-up or non-local progressive will be censored at the date of the last follow-up examination where no signs of local and loco-regional progression were observed.
Measured: 12 months PFS rate
Secondary outcomes (7)
Overall survival (OS)
Time interval (days) 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. Patients not reported dead or lost to follow-up will be censored at the date of the last follow-up or the time when last seen alive.
Measured: 12 months survival rate
Local PFS
lenght of time (days) till local disease progression
Measured: 12 months after treatment
Quality of life (QLQ-C30)
Units on a Scale
Measured: up to 12 months after treatment
Loco-regional recurrence
Time to loco-regional recurrence
Measured: up to 12 months after treatment
Quality of life (BN20)
Units on a Scale
Measured: up to 12 months after treatment
Local recurrence
Time to local recurrence
Measured: up to 12 months after treatment
Loco-regional PFS
lenght of time (days) till loco-regional disease progression
Measured: 12 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2017
- Study start1 Feb 2018
- Primary completion30 May 2021
- Study completion8 Jul 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 Metastases, AdultStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 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
- NCT03285932
- Sponsor's protocol ID
- ESTRON
- Acronym
- ESTRON
- Status last verified
- Nov 2022
- First submitted
- 13 Sep 2017
- Last updated
- 3 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, Xu W, Sahgal A. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012 Apr 18;2012(4):CD003869. doi: 10.1002/14651858.CD003869.pub3.
PubMed 22513917Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004 Jul 15;22(14):2865-72. doi: 10.1200/JCO.2004.12.149.
PubMed 15254054Linskey 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 19960227Soliman H, Das S, Larson DA, Sahgal A. Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases. Oncotarget. 2016 Mar 15;7(11):12318-30. doi: 10.18632/oncotarget.7131.
PubMed 26848525Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012 Feb 1;30(4):419-25. doi: 10.1200/JCO.2011.38.0527. Epub 2011 Dec 27.
PubMed 22203767Nieder C, Grosu AL, Gaspar LE. Stereotactic radiosurgery (SRS) for brain metastases: a systematic review. Radiat Oncol. 2014 Jul 12;9:155. doi: 10.1186/1748-717X-9-155.
PubMed 25016309Gans JH, Raper DM, Shah AH, Bregy A, Heros D, Lally BE, Morcos JJ, Heros RC, Komotar RJ. The role of radiosurgery to the tumor bed after resection of brain metastases. Neurosurgery. 2013 Mar;72(3):317-25; discussion 325-6. doi: 10.1227/NEU.0b013e31827fcd60.
PubMed 23208065Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, Raco A, Bozzao A, Maurizi Enrici R. Multidose stereotactic radiosurgery (9 Gy x 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):623-9. doi: 10.1016/j.ijrobp.2013.03.037. Epub 2013 May 15.
PubMed 23683828Connolly EP, Mathew M, Tam M, King JV, Kunnakkat SD, Parker EC, Golfinos JG, Gruber ML, Narayana A. Involved field radiation therapy after surgical resection of solitary brain metastases--mature results. Neuro Oncol. 2013 May;15(5):589-94. doi: 10.1093/neuonc/nos328. Epub 2013 Mar 3.
PubMed 23460323Wang CC, Floyd SR, Chang CH, Warnke PC, Chio CC, Kasper EM, Mahadevan A, Wong ET, Chen CC. Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity after excision of large cerebral metastasis: efficacy and safety of an 800 cGy x 3 daily fractions regimen. J Neurooncol. 2012 Feb;106(3):601-10. doi: 10.1007/s11060-011-0697-z. Epub 2011 Aug 31.
PubMed 21879395Jensen CA, Chan MD, McCoy TP, Bourland JD, deGuzman AF, Ellis TL, Ekstrand KE, McMullen KP, Munley MT, Shaw EG, Urbanic JJ, Tatter SB. Cavity-directed radiosurgery as adjuvant therapy after resection of a brain metastasis. J Neurosurg. 2011 Jun;114(6):1585-91. doi: 10.3171/2010.11.JNS10939. Epub 2010 Dec 17.
PubMed 21166567Iorio-Morin C, Masson-Cote L, Ezahr Y, Blanchard J, Ebacher A, Mathieu D. Early Gamma Knife stereotactic radiosurgery to the tumor bed of resected brain metastasis for improved local control. J Neurosurg. 2014 Dec;121 Suppl:69-74. doi: 10.3171/2014.7.GKS141488.
PubMed 25434939Kelly PJ, Lin YB, Yu AY, Alexander BM, Hacker F, Marcus KJ, Weiss SE. Stereotactic irradiation of the postoperative resection cavity for brain metastasis: a frameless linear accelerator-based case series and review of the technique. Int J Radiat Oncol Biol Phys. 2012 Jan 1;82(1):95-101. doi: 10.1016/j.ijrobp.2010.10.043. Epub 2010 Dec 17.
PubMed 21168282Atalar B, Modlin LA, Choi CY, Adler JR, Gibbs IC, Chang SD, Harsh GR 4th, Li G, Nagpal S, Hanlon A, Soltys SG. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):713-8. doi: 10.1016/j.ijrobp.2013.07.034. Epub 2013 Sep 18.
PubMed 24054875Ojerholm E, Lee JY, Thawani JP, Miller D, O'Rourke DM, Dorsey JF, Geiger GA, Nagda S, Kolker JD, Lustig RA, Alonso-Basanta M. Stereotactic radiosurgery to the resection bed for intracranial metastases and risk of leptomeningeal carcinomatosis. J Neurosurg. 2014 Dec;121 Suppl:75-83. doi: 10.3171/2014.6.GKS14708.
PubMed 25434940
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
- Evaluation of Stereotactic Radiotherapy of the Resection Cavity After Surgery of Brain Metastases Compared to Post-operative Whole-brain Radiotherapy
- ClinicalTrials.gov ID
- NCT03285932
- Acronym / sponsor ID
- ESTRON / ESTRON
- Conditions
- Brain Metastases, Adult
- Keywords
- Brain Metastase, Radiation of resection cavity, WBRT (whole brain radiotherapy), SRS (stereotactic radiosurgery)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Juergen DebusUniversity, hospital or other
- Collaborators
- Heidelberg University
- Study start
- 1 Feb 2018 (actual)
- Primary completion
- 30 May 2021 (actual)
- Study completion
- 8 Jul 2021 (actual)
- First posted
- 18 Sep 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.
In advanced cancer disease brain metastases are common, difficult to treat, and are associated with a poor prognosis. As new local and systemic therapies are eventually resulting in improved survival and quality of life for patients with brain metastases, negative neurocognitive effects of radiation therapy are becoming increasingly important as well as good loco-regional disease control of brain metastases.
Concerning treatment, brain metastases remain a major clinical problem and a multidisciplinary approach to management should be adopted. Neurosurgical resection with postoperative whole brain radiotherapy (WBRT) is one major treatment option in solitary or symptomatic brain metastases. Furthermore, WBRT is recommended for multiple brain metastases. For a limited number of brain metastases stereotactic radiosurgery (SRS) has been established as a highly effective treatment alternative.
Recently, a new treatment approach combing neurosurgery with postoperative stereotactic radiotherapy (SRT) of the resection cavity is emerging. Based on available evidence, postoperative SRT of the resection cavity improves local control following surgery, reduces the number of patients who require whole brain radiotherapy, and is well tolerated (1).
This protocol is aimed at primarily evaluating the safety and toxicity profile of SRT to the resection cavity following neurosurgical resection combined with SRT of potentially further unresected brain metastases, compared to postoperative whole-brain radiotherapy (WBRT). Secondary, the local effect of SRT in patients with brain metastases will be assessed by measuring time to local recurrence (LR), local and loco-regional progression-free survival (PFS).
Additional systemic treatment will be carried out according to the standards of the National Center for Tumor Therapy (NCT).
Detailed description
Scientific Background: Brain metastases (BM) represent a significant healthcare problem. It is estimated that 20% to 40% of patients with cancer will develop metastatic cancer to the brain during the course of their illness 1. The most common primary sites are lung, melanoma, renal, breast and colorectal cancer 2. Options for patients with brain metastases had been limited to whole brain radiotherapy (WBRT) or supportive care alone, and systemic chemotherapy was often discontinued. Historically, the best possible supportive care or whole-brain radiotherapy (WBRT) were the standard of care 1 aiming at temporary symptom relief. For WBRT, efficacy in symptom relief but also in prolongation of the median survival time by 3-6 months is well documented. To date, microsurgical approaches and SRS, both proved to be safe and efficient, offer alternative treatment options that potentially meet these concerns 6,7. After proving its efficacy in achieving local tumor control in the treated volume, SRS was used as a stand-alone treatment option in patients with oligometastases (one to four metastases) in the brain. There is a rapidly expanding recent body of literature on outcomes of single-fraction SRS or hypofractionated SRS targeting the resection cavity after surgical resection of BM. Several retrospective series assessed the efficacy and safety of postoperative SRS to the resection cavity 9 aiming at an enhanced local tumor control but also at avoidance of the neurotoxic late effects of WBRT. WBRT followed by SRS of the tumor bed leads to 1-year local control rates of 70-93 %, which is comparable to results after surgery followed by WBRT. Median survival was 12-18 months with a 1-year incidence of new metastases in the brain of 45-60 %.
Trial Objectives: This protocol is primarily aimed at evaluating the safety and toxicity profile of SRS following neurosurgical resection and compares it to that of WBRT as the established standard of care. Secondary, the local effect of radiation therapy in patients with brain metastases will be assessed by measuring time to local and loco-regional recurrence, local and loco-regional PFS and overall survival at 12 months after treatment.
Patients´Selection: Patients with the diagnosis of brain metastases from solid tumors that have undergone neurosurgical resection of one brain metastasis will be evaluated and screened for the protocol. 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 post-operative contrast-enhanced cranial MRI imaging and imaging will be assessed by a radiologist. All available MRI sequences, including SPACE will be taken into consideration for the definition of treatment target lesions. Patients for whom the post-operative MRI reveals more than 10 suspect intracranial lesions (all sequences taken into account) will not be included in the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Post-operative SRS of resection cavity | Experimental | Radiation: post-operative stereotactic radiosurgery (SRS)High-resolution contrast-enhanced post-operative MRI imaging in preparation for Cyberknife SRS. Cyberknife SRS of the resection cavity and all potential additional metastases diagnosed in the treatment planning MRI (up to 10 lesions) Resection cavity: 7 x 5 Gy @ 95%-isodose Potential additional brain metastases: 20 Gy @ 70%-isodose (lesions < 2 cm max. diameter) 18 Gy @ 70%-isodose (lesions 2 - 3 cm max. diameter) 6 x 5 Gy @ 70%-isodose (lesions > 3 cm max. diameter) |
| Post-operative WBRT | Other | Radiation: Whole brain radiotherapy (WBRT)Post-operative WBRT will be performed according to the following dose regimen: 10 x 3 Gy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- histologically confirmed solid cancer
- MRI confirmed cerebral metastases
- Neurosurgical resection of one cerebral metastasis
- age ≥ 18 years of age
- Karnofsky Performance Score >60
Key exclusion criteria (6 listed)
- refusal of the patients to take part in the study
- previous radiotherapy to the brain
- > 10 unresected brain metastases in postoperative MRI
- Patients who have not yet recovered from acute toxicities of prior therapies
- known carcinoma < 2 years ago (excluding carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
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 |
|---|---|---|
| post-operative stereotactic radiosurgery (SRS)For radiosurgery, patients will be immobilized. Treatment planning including the MRI and planning CT should be performed 1 -2 weeks before SRT and treatment finished at latest 3-4 weeks after surgery. Planning should be as close to SRT as possible. Organs at risk such as the brain stem, optic nerves, chiasm and spinal cord will be contoured. The Clinical Target Volume 1 (CTV1) will be defined as the resection cavity based on MRI and CT including T1 contrast enhanced changes around the resection cavity. The Clinical Target Volume 2 (CTV2) will be defined as a 3mm margin added to CTV1 by isotropic expansion and slightly adjusted as deemed appropriated by the experienced contouring physician. The Planning Target Volume (PTV) will be an additional margin of 1mm added to CTV2 by isotropic expansion. Treatment planning will be performed using Accuray's Multiplan or subsequent approved treatment planning systems for Cyberknife. | Radiation | Post-operative SRS of resection cavity |
| Whole brain radiotherapy (WBRT)For WBRT, an individual head fixation mask is manufactured for each patient, and treatment planning is performed as virtual simulation or 3D-conformal RT planning based on CT-imaging. The portals include the whole brain with special focus as including the skull base areas and lamina cribrosa. For low infratentorial lesions, the treatment volume may include the whole brain down to the second cervical vertbra. RT will be applied with two portals (e.g. 87°and 273°) using a 6 MeV linear accelerator. For WBRT, a total dose of 30 Gy in 3 Gy fractions will be applied. | Radiation | Post-operative WBRT |
Primary outcome
neurological progression-free survival (PFS)
Time frame: 12 months PFS rate
Neurologic progression-free survival in follow-up imaging is the primary endpoint of the study. The duration is defined as the time interval between the date start of RT and the date of local and loco-regional progression or death, or the date of leaving the study without local and loco-regional progression (e.g., lost to follow up non-local progression) whatever occurs first. Patients not reported local and loco-regional progressive or dead, or lost to follow-up or non-local progressive will be censored at the date of the last follow-up examination where no signs of local and loco-regional progression were observed.
7 secondary outcomes
Overall survival (OS)
Time frame: 12 months survival rate
Local PFS
Time frame: 12 months after treatment
Quality of life (QLQ-C30)
Time frame: up to 12 months after treatment
Loco-regional recurrence
Time frame: up to 12 months after treatment
Quality of life (BN20)
Time frame: up to 12 months after treatment
Local recurrence
Time frame: up to 12 months after treatment
Loco-regional PFS
Time frame: 12 months after treatment
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 22513917Tsao MN, Lloyd N, Wong RK, Chow E, Rakovitch E, Laperriere N, Xu W, Sahgal A. Whole brain radiotherapy for the treatment of newly diagnosed multiple brain metastases. Cochrane Database Syst Rev. 2012 Apr 18;2012(4):CD003869. doi: 10.1002/14651858.CD003869.pub3.
- Background: PubMed 15254054Barnholtz-Sloan JS, Sloan AE, Davis FG, Vigneau FD, Lai P, Sawaya RE. Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System. J Clin Oncol. 2004 Jul 15;22(14):2865-72. doi: 10.1200/JCO.2004.12.149.
- 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 26848525Soliman H, Das S, Larson DA, Sahgal A. Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases. Oncotarget. 2016 Mar 15;7(11):12318-30. doi: 10.18632/oncotarget.7131.
- Background: PubMed 22203767Sperduto PW, Kased N, Roberge D, Xu Z, Shanley R, Luo X, Sneed PK, Chao ST, Weil RJ, Suh J, Bhatt A, Jensen AW, Brown PD, Shih HA, Kirkpatrick J, Gaspar LE, Fiveash JB, Chiang V, Knisely JP, Sperduto CM, Lin N, Mehta M. Summary report on the graded prognostic assessment: an accurate and facile diagnosis-specific tool to estimate survival for patients with brain metastases. J Clin Oncol. 2012 Feb 1;30(4):419-25. doi: 10.1200/JCO.2011.38.0527. Epub 2011 Dec 27.
- Background: PubMed 25016309Nieder C, Grosu AL, Gaspar LE. Stereotactic radiosurgery (SRS) for brain metastases: a systematic review. Radiat Oncol. 2014 Jul 12;9:155. doi: 10.1186/1748-717X-9-155.
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- Background: PubMed 23683828Minniti G, Esposito V, Clarke E, Scaringi C, Lanzetta G, Salvati M, Raco A, Bozzao A, Maurizi Enrici R. Multidose stereotactic radiosurgery (9 Gy x 3) of the postoperative resection cavity for treatment of large brain metastases. Int J Radiat Oncol Biol Phys. 2013 Jul 15;86(4):623-9. doi: 10.1016/j.ijrobp.2013.03.037. Epub 2013 May 15.
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- 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 Phase 2 study testing post-operative stereotactic radiosurgery (SRS) and Whole brain radiotherapy (WBRT) in people with Brain Metastases, Adult, 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 8 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: 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
neurological progression-free survival (PFS) (time frame: 12 months PFS rate). 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 NCT03285932, 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.