Brain MetastasesNCT04847284
Intraoperative Radiotherapy in Patients With Brain Metastases
A study testing Intraoperative radiotherapy in people with Brain Metastases, run by Parc de Salut Mar at 1 site in Spain.
Trial summary
Intraoperative radiotherapy (IORT) is a new alternative for local radiotherapy with the advantages of dose escalation, reduced overall treatment time, and enhanced patient convenience, however the degree of efficacy is unknown, as well as and which is the most efficient dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases
- What is being tested?
- Intraoperative radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteSpain
- Study dates
- 5 May 2021to Dec 2025
- 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
- Age ≥ 18 years
- Karnofsky Performance Status ≥ 70
- Newly diagnosed cerebral or cerebellar lesion (contrast enhancing on a T1-weighted MRI scan) amenable to total resection with no dural attachment
- Frozen section confirming a metastasis of an extracranial ( Central Nervous System i.e. non-CNS) tumor
- Adequate distance to optic nerve(s), chiasm and brainstem (organs at risk for radiotherapy)
- Adequate birth control
Who cannot join
- Leptomeningeal spread and dural attachment (assessed pre- and intraoperatively)
- Frozen section reveals primary CNS tumor, lymphoma, SCLC (Small-cell lung cancer) or germinoma
- More than one brain metastasis
- Psychiatric or social condition potentially interfering with compliance
- Contraindication against anesthesia, surgery, MRI and/or contrast agents
- Pregnant or breast-feeding women
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Hospital del Mar
Barcelona, 08003
Palmira Foro Arnalot, MD, PhD, 93248357, pforo@parcdesalutmar.cat
Palmira Foro Arnalot, MD, PhD
About this study
Intraoperative radiotherapy (IORT) is a new alternative for local radiotherapy with the advantages of dose escalation, reduced overall treatment time, and enhanced patient convenience, however the degree of efficacy is unknown, as well as and which is the most efficient dose.
The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.
Read the detailed description
- INTRODUCTION Brain metastases occur in roughly 30% of all cancer patients during their course of disease. Their incidence is believed to rise due to the aging population that develops more cancer per se, an increase in overall survival due to more effective extracranial therapies but with only few (novel) substances crossing the blood-brain barrier and more broadly available and more advanced imaging techniques. Neurosurgical treatment remains a cornerstone in the management of brain metastasis, especially for lesions causing mass effects or neurological deficits or in case tissue is necessary to establish a diagnosis. As local recurrence rates are as high as 50-60% after surgical resection alone, adjuvant therapies to prevent such are necessary. Whole brain radiotherapy (WBRT) does not influence survival but rather impairs neurocognitive functions and, as histologic in-depth exams of cavity borders showed that most brain metastases infiltrate only 0.3-1.2 mm into the surrounding healthy brain tissue, therefore treatment is to date usually confined to the cavity margin. Thus, the currently recommended standard of care is post-operative stereotactic radiosurgery (SRS) to the resection cavity. One of the drawbacks of this modality is the incidence of radionecrosis, especially in large tumor volumes. As an alternative to radiosurgery, hypofractionated local radiotherapy is also used, reducing the risk of radionecrosis in large volumes. There are no prospective randomized studies comparing both techniques. The need to find a modality of radiotherapy that achieves al least the efficacy of radiosurgery or hypofractionated local radiotherapy, without the disadvantages thereof, makes IORT as a possible treatment alternative. The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.
- OBJECTIVES Primary Objective
- Median local progression free survival (lPFS), defined as time span (in months) between surgery and recurrence within a 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
- Radiation-related (acute / late) neurotoxicity, assessed by regular neurological examinations and serial MRI scans. Secondary objectives
- Median regional PFS (rPFS), resembling the time (in months) from surgery to any progression outside of the 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
- Global PFS (gPFS), defined as the time (in months) from surgery to any intra- and extracranial tumor progress.
- Median overall survival (OS), defined as the time (in months) from surgery of brain metastases to death from by any cause.
- DESIGN
This trial is an open, single arm, single institution, prospective trial to determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases. A total of 25 patients will be included.
- Conditions
- Brain Metastases
- Being tested
- Intraoperative radiotherapy
- Keywords
- Brain metastases, Intraoperative radiotherapy, Intrabeam
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intraoperative radiotherapyRadiation
Intraoperative radiotherapy application immediately following resection of brain metastases.
| Study group | Role | What they receive |
|---|---|---|
| Single arms | Experimental | To determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases Receives: Radiation: Intraoperative radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median local progression free survival (lPFS)
Recurrence within a 0.5 cm margin around the resection cavity, assessed by serial magnetic resonance imaging (MRI scans) and response assessment criteria in neuro-oncology (RANO)
Measured: 6 months from the date of surgery.
Radiation-related acute neurotoxicity
Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity
- Acute toxicity: cerebral edema
Measured: 3 months from the date of surgery.
Radiation-related late neurotoxicity
Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity
- Late toxicity: radionecrosis.
Measured: 6 months from the date of surgery.
Secondary outcomes (3)
Median regional PFS (rPFS)
To any progression outside of the 0.5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment in neuro-oncology .
Measured: 6 months from the date of surgery
Global PFS (gPFS)
The time (in months) from surgery to any intra- and extracranial tumor progress
Measured: 6 months from the date of surgery
Median overall survival (OS)
The time (in months) from surgery of brain metastases to death from by any cause.
Measured: 6 months from the date of surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2021
- Study start5 May 2021
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Parc de Salut Mar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04847284
- Sponsor's protocol ID
- 2020/9548/I
- Status last verified
- Oct 2024
- First submitted
- 25 Mar 2021
- Last updated
- 6 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Giordano FA, Brehmer S, Murle B, Welzel G, Sperk E, Keller A, Abo-Madyan Y, Scherzinger E, Clausen S, Schneider F, Herskind C, Glas M, Seiz-Rosenhagen M, Groden C, Hanggi D, Schmiedek P, Emami B, Souhami L, Petrecca K, Wenz F. Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial. Neurosurgery. 2019 Jan 1;84(1):41-49. doi: 10.1093/neuros/nyy018.
PubMed 29528443Weil RJ, Mavinkurve GG, Chao ST, Vogelbaum MA, Suh JH, Kolar M, Toms SA. Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes. J Neurosurg. 2015 Apr;122(4):825-32. doi: 10.3171/2014.11.JNS1449. Epub 2015 Jan 23.
PubMed 25614945Cifarelli CP, Brehmer S, Vargo JA, Hack JD, Kahl KH, Sarria-Vargas G, Giordano FA. Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study. J Neurooncol. 2019 Nov;145(2):391-397. doi: 10.1007/s11060-019-03309-6. Epub 2019 Oct 25.
PubMed 31654248Vargo JA, Sparks KM, Singh R, Jacobson GM, Hack JD, Cifarelli CP. Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery. J Neurooncol. 2018 Nov;140(2):413-420. doi: 10.1007/s11060-018-2968-4. Epub 2018 Aug 9.
PubMed 30094718
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraoperative Radiotherapy in Patients With Brain Metastases
- ClinicalTrials.gov ID
- NCT04847284
- Acronym / sponsor ID
- 2020/9548/I
- Conditions
- Brain Metastases
- Keywords
- Brain metastases, Intraoperative radiotherapy, Intrabeam
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Parc de Salut MarUniversity, hospital or other
- Study start
- 5 May 2021 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 19 Apr 2021 (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.
Intraoperative radiotherapy (IORT) is a new alternative for local radiotherapy with the advantages of dose escalation, reduced overall treatment time, and enhanced patient convenience, however the degree of efficacy is unknown, as well as and which is the most efficient dose.
The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.
Detailed description
- INTRODUCTION Brain metastases occur in roughly 30% of all cancer patients during their course of disease. Their incidence is believed to rise due to the aging population that develops more cancer per se, an increase in overall survival due to more effective extracranial therapies but with only few (novel) substances crossing the blood-brain barrier and more broadly available and more advanced imaging techniques. Neurosurgical treatment remains a cornerstone in the management of brain metastasis, especially for lesions causing mass effects or neurological deficits or in case tissue is necessary to establish a diagnosis. As local recurrence rates are as high as 50-60% after surgical resection alone, adjuvant therapies to prevent such are necessary. Whole brain radiotherapy (WBRT) does not influence survival but rather impairs neurocognitive functions and, as histologic in-depth exams of cavity borders showed that most brain metastases infiltrate only 0.3-1.2 mm into the surrounding healthy brain tissue, therefore treatment is to date usually confined to the cavity margin. Thus, the currently recommended standard of care is post-operative stereotactic radiosurgery (SRS) to the resection cavity. One of the drawbacks of this modality is the incidence of radionecrosis, especially in large tumor volumes. As an alternative to radiosurgery, hypofractionated local radiotherapy is also used, reducing the risk of radionecrosis in large volumes. There are no prospective randomized studies comparing both techniques. The need to find a modality of radiotherapy that achieves al least the efficacy of radiosurgery or hypofractionated local radiotherapy, without the disadvantages thereof, makes IORT as a possible treatment alternative. The objective of this study is to evaluate the efficacy and safety of IORT in patients with surgical excision of brain metastases at a dose of 20 Gy is at least as effective and safe as other forms of radiation therapy in patients with resection of brain metastases.
- OBJECTIVES Primary Objective
- Median local progression free survival (lPFS), defined as time span (in months) between surgery and recurrence within a 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
- Radiation-related (acute / late) neurotoxicity, assessed by regular neurological examinations and serial MRI scans. Secondary objectives
- Median regional PFS (rPFS), resembling the time (in months) from surgery to any progression outside of the 0,5 cm margin around the resection cavity, assessed by serial MRI scans and RANO response assessment criteria for brain metastases .
- Global PFS (gPFS), defined as the time (in months) from surgery to any intra- and extracranial tumor progress.
- Median overall survival (OS), defined as the time (in months) from surgery of brain metastases to death from by any cause.
- DESIGN
This trial is an open, single arm, single institution, prospective trial to determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases. A total of 25 patients will be included.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single arms | Experimental | Radiation: Intraoperative radiotherapyTo determine the efficiency and safety of IORT with low-energy photons to the cavity after resection of brain metastases |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years
- Karnofsky Performance Status ≥ 70
- Newly diagnosed cerebral or cerebellar lesion (contrast enhancing on a T1-weighted MRI scan) amenable to total resection with no dural attachment
- Frozen section confirming a metastasis of an extracranial ( Central Nervous System i.e. non-CNS) tumor
- Adequate distance to optic nerve(s), chiasm and brainstem (organs at risk for radiotherapy)
Key exclusion criteria (6 listed)
- Leptomeningeal spread and dural attachment (assessed pre- and intraoperatively)
- Frozen section reveals primary CNS tumor, lymphoma, SCLC (Small-cell lung cancer) or germinoma
- More than one brain metastasis
- Psychiatric or social condition potentially interfering with compliance
- Contraindication against anesthesia, surgery, MRI and/or contrast agents
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 |
|---|---|---|
| Intraoperative radiotherapyIntraoperative radiotherapy application immediately following resection of brain metastases. | Radiation | Single arms |
Primary outcome
Median local progression free survival (lPFS)
Time frame: 6 months from the date of surgery.
Recurrence within a 0.5 cm margin around the resection cavity, assessed by serial magnetic resonance imaging (MRI scans) and response assessment criteria in neuro-oncology (RANO)
Radiation-related acute neurotoxicity
Time frame: 3 months from the date of surgery.
Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity - Acute toxicity: cerebral edema
Radiation-related late neurotoxicity
Time frame: 6 months from the date of surgery.
Neurotoxicity related to radiotherapy evaluated according to the scale of the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Score from 0 to 5, with 5 being the worst toxicity - Late toxicity: radionecrosis.
3 secondary outcomes
Median regional PFS (rPFS)
Time frame: 6 months from the date of surgery
Global PFS (gPFS)
Time frame: 6 months from the date of surgery
Median overall survival (OS)
Time frame: 6 months from the date of surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2025.
- Results publication: PubMed 29528443Giordano FA, Brehmer S, Murle B, Welzel G, Sperk E, Keller A, Abo-Madyan Y, Scherzinger E, Clausen S, Schneider F, Herskind C, Glas M, Seiz-Rosenhagen M, Groden C, Hanggi D, Schmiedek P, Emami B, Souhami L, Petrecca K, Wenz F. Intraoperative Radiotherapy in Newly Diagnosed Glioblastoma (INTRAGO): An Open-Label, Dose-Escalation Phase I/II Trial. Neurosurgery. 2019 Jan 1;84(1):41-49. doi: 10.1093/neuros/nyy018.
- Results publication: PubMed 25614945Weil RJ, Mavinkurve GG, Chao ST, Vogelbaum MA, Suh JH, Kolar M, Toms SA. Intraoperative radiotherapy to treat newly diagnosed solitary brain metastasis: initial experience and long-term outcomes. J Neurosurg. 2015 Apr;122(4):825-32. doi: 10.3171/2014.11.JNS1449. Epub 2015 Jan 23.
- Results publication: PubMed 31654248Cifarelli CP, Brehmer S, Vargo JA, Hack JD, Kahl KH, Sarria-Vargas G, Giordano FA. Intraoperative radiotherapy (IORT) for surgically resected brain metastases: outcome analysis of an international cooperative study. J Neurooncol. 2019 Nov;145(2):391-397. doi: 10.1007/s11060-019-03309-6. Epub 2019 Oct 25.
- Results publication: PubMed 30094718Vargo JA, Sparks KM, Singh R, Jacobson GM, Hack JD, Cifarelli CP. Feasibility of dose escalation using intraoperative radiotherapy following resection of large brain metastases compared to post-operative stereotactic radiosurgery. J Neurooncol. 2018 Nov;140(2):413-420. doi: 10.1007/s11060-018-2968-4. Epub 2018 Aug 9.
- Individual participant dataSharing planned: No
Related trials for Brain Metastases
RecruitingPhase 2
BrAin Metastasis in tripLe Negateive Breast Cancer: IvoneScimab and Trop2 ADC
Triple-Negative Breast Cancer (TNBC), Brain Metastases
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
Epidural Hydroxyethyl Starch for Post-Dural Puncture Headache in Parturients
Parturients, Accidental Puncture of Dura During Anaesthesia
RecruitingObservational study
Collection of CSF Samples From Participants With Metastatic Triple Negative Breast Cancer (TNBC) and HER2+ Breast Cancer With no Prior History Nor Active Radiographically Detectable Brain Metastases
Breast Cancer, Breast Carcinoma
RecruitingPhase 2/3
RO7771950 Versus Tucatinib in Combination With Trastuzumab and Capecitabine in People With Locally Advanced or Metastatic Breast Cancer That is Human Epidermal Growth Factor Receptor 2 (HER2)-Positive
HER2-positive Breast Cancer
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intraoperative radiotherapy in people with Brain Metastases, run by Parc de Salut Mar at 1 site in Spain.
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 6 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 6 Jun 2025. 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 Spain. 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 Palmira Foro, MD, PhD (628118443, pforo@psmar.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Median local progression free survival (lPFS) (time frame: 6 months from the date of surgery.). The study lists 3 primary outcomes in all. 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 NCT04847284, which also lists 4 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 6 Jun 2025.