Brain Metastases, AdultNCT04785521
Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery
An observational study of Brain Metastases, Adult, run by IRCCS San Raffaele at 1 site in Italy.
Trial summary
Brain metastases (BM) represents a devastating clinical reality, carrying an estimated survival time of less than one year. Number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. 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?
- Stereotactic radiosurgery and Blood samples
- Type of treatment
- Surgery or procedure
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 1 Jul 2020to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Target group: Adult patients affected by melanoma, breast or lung cancer BM of new diagnosis as confirmed by MRI ongoing SRS-GK treatment. Control group 1: Adult patients affected by melanoma, breast or lung cancer without BM. Control group 2: Adult patients affected by intracranial extra-axial benign tumor as confirmed by MRI ongoing SRS-GK treatment.
Who may be able to join
- Adult patients carrying melanoma, breast or lung cancer BM of new diagnosis
- Patients eligible to SRS-GK treatment
- Adult patients carrying melanoma, breast or lung cancer without BM
- Adult patients carrying intracranial extra-axial benign tumor
- Patients eligible to SRS-GK treatment
Who cannot join
- Acute or chronic liver disease
- Severe anemia (Hb <8g/dl)
- Pregnant or breastfeeding patient
- Pediatric patients
- Patients not able to express informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Brain metastases (BM) represents a devastating clinical reality, carrying an estimated survival time of less than one year. Number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. BM are indeed the most frequent neoplasm in the central nervous system (CNS) and is estimated that up to 14% of all newly diagnosed cancers will metastasize to the brain. A number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. Present knowledge regarding alterations in Glutamate (Glu) homeostasis and BM is poor. This study aims at investigating Glu balance in BM patients and providing supporting evidence to the identification of new putative biomarkers to be used as potential therapeutic targets.
Read the detailed description
Experimental procedure:
Serum levels of glutamic oxaloacetic transaminase (GOT1), glutamate Pyruvate Transaminase (GPT) and lactate dehydrogenase (LDH) levels and serum glutamate, aspartate and lactate levels of a total of 100 patients will be collected and divided in three different groups:
- A: BM group (n=50), patients affected by BM from lung, breast and melanoma, candidates to SRS
- B: Control group 1 (n=25), patients with the same primary controlled tumors without nor brain nor extracranial metastases
- C: Control group 2 (n=25), patients with benign intracranial lesions candidates to SRS treatment.
In A) and C) serum GOT1, GPT and LDH levels and serum glutamate, aspartate, lactate levels will be evaluated before and after SRS treatment (at 3, 6 and 9 months follow-up).
In B) serum biomarkers levels will be only collected at baseline.
- Oncological and imaging data will be collected during follow-up in patients enrolled in the present studies. MRI imaging will be performed at definite timepoints (baseline and 3, 6 and 9 months follow-up).
Serum levels of markers will be analyzed in each group and results will be compared between them. Moreover, MRI changes and oncological relevant outcomes will be investigated.
- Conditions
- Brain Metastases, Adult
- Being tested
- Stereotactic radiosurgery, Blood samples
- Keywords
- Brain metastases, Glutamate, Stereotactic radiosurgery
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic radiosurgeryRadiation
Gamma Knife stereotactic radiosurgery (SRS-GK)
Blood samplesDiagnostic test
Serum Glu levels and Glu-regulation markers assessed prior to and following SRS-GK in BM or benign lesions or at baseline in non-BM patients.
| Study group | Role | What they receive |
|---|---|---|
| BM patients | Adult patients carrying new diagnosed BM confirmed by MRI Receives: Radiation: Stereotactic radiosurgery; Diagnostic Test: Blood samples | |
| No BM patients | Adult patients carrying extracranial tumor without BM as confirmed by MRI Receives: Diagnostic Test: Blood samples | |
| Benign lesion patients | Adult patients carrying intracranial extra-axial tumor as as confirmed by MRI Receives: Radiation: Stereotactic radiosurgery; Diagnostic Test: Blood samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, before SRS treatment.
GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl.
Measured: Baseline (pre-SRS);
Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, after SRS treatment.
GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl.
Measured: Baseline (pre-SRS) and at 3, 6 and 9 months
Serum markers determination in melanoma, lung or breast cancer patients without BM.
Comparison of serum GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels between BM and non-BM patients. All measures in mg/dl.
Measured: Baseline
Serum markers determination in patients carrying benign intracranial lesions before and after SRS treatment.
Comparison of serum GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels between BM and benign lesion patients. All measures in mg/dl.
Measured: Baseline (pre-SRS) and at 3, 6 and 9 months
Secondary outcomes (1)
Studying correlation of serum markers levels with MRI changes following SRS-GK
Correlation between trends of markers and incidence of MRI changes.
Measured: 3, 6 and 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2021
- Study start1 Jul 2020
- Primary completion31 Jul 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Brain Metastases, AdultStudies of the same condition, open and under way.
- More trials run by IRCCS San RaffaeleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pietro Mortini, MD, Prof., IRCCS San Raffaele
- Investigators
- Pietro Mortini, MD, Prof., Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04785521
- Sponsor's protocol ID
- NCH04-2020
- Status last verified
- Jun 2025
- First submitted
- 2 Mar 2021
- Last updated
- 11 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lowery FJ, Yu D. Brain metastasis: Unique challenges and open opportunities. Biochim Biophys Acta Rev Cancer. 2017 Jan;1867(1):49-57. doi: 10.1016/j.bbcan.2016.12.001. Epub 2016 Dec 6.
PubMed 27939792Franzin A, Snider S, Picozzi P, Bolognesi A, Serra C, Vimercati A, Passarin O, Mortini P. Evaluation of different score index for predicting prognosis in gamma knife radiosurgical treatment for brain metastasis. Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):707-13. doi: 10.1016/j.ijrobp.2008.08.062. Epub 2008 Dec 25.
PubMed 19095375Robert SM, Sontheimer H. Glutamate transporters in the biology of malignant gliomas. Cell Mol Life Sci. 2014 May;71(10):1839-54. doi: 10.1007/s00018-013-1521-z. Epub 2013 Nov 27.
PubMed 24281762Miladinovic T, Nashed MG, Singh G. Overview of Glutamatergic Dysregulation in Central Pathologies. Biomolecules. 2015 Nov 11;5(4):3112-41. doi: 10.3390/biom5043112.
PubMed 26569330Sharma MK, Seidlitz EP, Singh G. Cancer cells release glutamate via the cystine/glutamate antiporter. Biochem Biophys Res Commun. 2010 Jan 1;391(1):91-5. doi: 10.1016/j.bbrc.2009.10.168. Epub 2009 Nov 5.
PubMed 19896463Zeng Q, Michael IP, Zhang P, Saghafinia S, Knott G, Jiao W, McCabe BD, Galvan JA, Robinson HPC, Zlobec I, Ciriello G, Hanahan D. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature. 2019 Sep;573(7775):526-531. doi: 10.1038/s41586-019-1576-6. Epub 2019 Sep 18.
PubMed 31534217Willard SS, Koochekpour S. Glutamate signaling in benign and malignant disorders: current status, future perspectives, and therapeutic implications. Int J Biol Sci. 2013 Aug 9;9(7):728-42. doi: 10.7150/ijbs.6475. eCollection 2013.
PubMed 23983606Gagliardi F, Roncelli F, Snider S, De Domenico P, Barzaghi LR, Bulotta A, Ogliari FR, Bandiera A, Zuber V, Pompeo E, Klungtvedt V, Dall'Acqua S, Comai S, Mortini P, Ruban A. Circulating levels of glutamate predict brain disease in patients with advanced lung and breast cancer: a prospective study. J Neurooncol. 2025 Nov;175(2):825-836. doi: 10.1007/s11060-025-05182-y. Epub 2025 Jul 28.
PubMed 40720079
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery
- ClinicalTrials.gov ID
- NCT04785521
- Acronym / sponsor ID
- NCH04-2020
- Conditions
- Brain Metastases, Adult
- Keywords
- Brain metastases, Glutamate, Stereotactic radiosurgery
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 1 Jul 2020 (actual)
- Primary completion
- 31 Jul 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 8 Mar 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.
Brain metastases (BM) represents a devastating clinical reality, carrying an estimated survival time of less than one year. Number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. BM are indeed the most frequent neoplasm in the central nervous system (CNS) and is estimated that up to 14% of all newly diagnosed cancers will metastasize to the brain. A number of reasons, including complicated tumor biology and difficulties in modeling metastatic cancer in brain microenvironment, do hinder research on this topic. Present knowledge regarding alterations in Glutamate (Glu) homeostasis and BM is poor. This study aims at investigating Glu balance in BM patients and providing supporting evidence to the identification of new putative biomarkers to be used as potential therapeutic targets.
Detailed description
Experimental procedure:
Serum levels of glutamic oxaloacetic transaminase (GOT1), glutamate Pyruvate Transaminase (GPT) and lactate dehydrogenase (LDH) levels and serum glutamate, aspartate and lactate levels of a total of 100 patients will be collected and divided in three different groups:
- A: BM group (n=50), patients affected by BM from lung, breast and melanoma, candidates to SRS
- B: Control group 1 (n=25), patients with the same primary controlled tumors without nor brain nor extracranial metastases
- C: Control group 2 (n=25), patients with benign intracranial lesions candidates to SRS treatment.
In A) and C) serum GOT1, GPT and LDH levels and serum glutamate, aspartate, lactate levels will be evaluated before and after SRS treatment (at 3, 6 and 9 months follow-up).
In B) serum biomarkers levels will be only collected at baseline.
- Oncological and imaging data will be collected during follow-up in patients enrolled in the present studies. MRI imaging will be performed at definite timepoints (baseline and 3, 6 and 9 months follow-up).
Serum levels of markers will be analyzed in each group and results will be compared between them. Moreover, MRI changes and oncological relevant outcomes will be investigated.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BM patients | – | Radiation: Stereotactic radiosurgery, Diagnostic Test: Blood samplesAdult patients carrying new diagnosed BM confirmed by MRI |
| No BM patients | – | Diagnostic Test: Blood samplesAdult patients carrying extracranial tumor without BM as confirmed by MRI |
| Benign lesion patients | – | Radiation: Stereotactic radiosurgery, Diagnostic Test: Blood samplesAdult patients carrying intracranial extra-axial tumor as as confirmed by MRI |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Target group: Adult patients affected by melanoma, breast or lung cancer BM of new diagnosis as confirmed by MRI ongoing SRS-GK treatment. Control group 1: Adult patients affected by melanoma, breast or lung cancer without BM. Control group 2: Adult patients affected by intracranial extra-axial benign tumor as confirmed by MRI ongoing SRS-GK treatment.
Key inclusion criteria (5 listed)
- Adult patients carrying melanoma, breast or lung cancer BM of new diagnosis
- Patients eligible to SRS-GK treatment
- Adult patients carrying melanoma, breast or lung cancer without BM
- Adult patients carrying intracranial extra-axial benign tumor
- Patients eligible to SRS-GK treatment
Key exclusion criteria (5 listed)
- Acute or chronic liver disease
- Severe anemia (Hb <8g/dl)
- Pregnant or breastfeeding patient
- Pediatric patients
- Patients not able to express informed consent
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 radiosurgeryGamma Knife stereotactic radiosurgery (SRS-GK) | Radiation | BM patients, Benign lesion patients |
| Blood samplesSerum Glu levels and Glu-regulation markers assessed prior to and following SRS-GK in BM or benign lesions or at baseline in non-BM patients. | Diagnostic test | BM patients, Benign lesion patients, No BM patients |
Primary outcome
Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, before SRS treatment.
Time frame: Baseline (pre-SRS);
GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl.
Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, after SRS treatment.
Time frame: Baseline (pre-SRS) and at 3, 6 and 9 months
GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels. All measures in mg/dl.
Serum markers determination in melanoma, lung or breast cancer patients without BM.
Time frame: Baseline
Comparison of serum GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels between BM and non-BM patients. All measures in mg/dl.
Serum markers determination in patients carrying benign intracranial lesions before and after SRS treatment.
Time frame: Baseline (pre-SRS) and at 3, 6 and 9 months
Comparison of serum GOT1, GPT and LDH levels and serum glutamate, aspartate and lactate levels between BM and benign lesion patients. All measures in mg/dl.
1 secondary outcome
Studying correlation of serum markers levels with MRI changes following SRS-GK
Time frame: 3, 6 and 9 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2025.
- Background: PubMed 27939792Lowery FJ, Yu D. Brain metastasis: Unique challenges and open opportunities. Biochim Biophys Acta Rev Cancer. 2017 Jan;1867(1):49-57. doi: 10.1016/j.bbcan.2016.12.001. Epub 2016 Dec 6.
- Background: PubMed 19095375Franzin A, Snider S, Picozzi P, Bolognesi A, Serra C, Vimercati A, Passarin O, Mortini P. Evaluation of different score index for predicting prognosis in gamma knife radiosurgical treatment for brain metastasis. Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):707-13. doi: 10.1016/j.ijrobp.2008.08.062. Epub 2008 Dec 25.
- Background: PubMed 24281762Robert SM, Sontheimer H. Glutamate transporters in the biology of malignant gliomas. Cell Mol Life Sci. 2014 May;71(10):1839-54. doi: 10.1007/s00018-013-1521-z. Epub 2013 Nov 27.
- Background: PubMed 26569330Miladinovic T, Nashed MG, Singh G. Overview of Glutamatergic Dysregulation in Central Pathologies. Biomolecules. 2015 Nov 11;5(4):3112-41. doi: 10.3390/biom5043112.
- Background: PubMed 19896463Sharma MK, Seidlitz EP, Singh G. Cancer cells release glutamate via the cystine/glutamate antiporter. Biochem Biophys Res Commun. 2010 Jan 1;391(1):91-5. doi: 10.1016/j.bbrc.2009.10.168. Epub 2009 Nov 5.
- Background: PubMed 31534217Zeng Q, Michael IP, Zhang P, Saghafinia S, Knott G, Jiao W, McCabe BD, Galvan JA, Robinson HPC, Zlobec I, Ciriello G, Hanahan D. Synaptic proximity enables NMDAR signalling to promote brain metastasis. Nature. 2019 Sep;573(7775):526-531. doi: 10.1038/s41586-019-1576-6. Epub 2019 Sep 18.
- Background: PubMed 23983606Willard SS, Koochekpour S. Glutamate signaling in benign and malignant disorders: current status, future perspectives, and therapeutic implications. Int J Biol Sci. 2013 Aug 9;9(7):728-42. doi: 10.7150/ijbs.6475. eCollection 2013.
- Derived from this study: PubMed 40720079Gagliardi F, Roncelli F, Snider S, De Domenico P, Barzaghi LR, Bulotta A, Ogliari FR, Bandiera A, Zuber V, Pompeo E, Klungtvedt V, Dall'Acqua S, Comai S, Mortini P, Ruban A. Circulating levels of glutamate predict brain disease in patients with advanced lung and breast cancer: a prospective study. J Neurooncol. 2025 Nov;175(2):825-836. doi: 10.1007/s11060-025-05182-y. Epub 2025 Jul 28.
- 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.
Pietro Mortini, MD, Prof. principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Brain Metastases, Adult, run by IRCCS San Raffaele at 1 site in Italy.
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 5 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 11 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 Italy. 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?
This study is still under way. Results are not available in the source record yet.
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?
Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, before SRS treatment. (time frame: Baseline (pre-SRS);). The study lists 4 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 NCT04785521, which also lists 8 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 11 Jun 2025.