Clinical trial NCT04785521: Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery
Official title: Glutamate Excitotoxicity in Brain Metastases From Lung, Breast and Melanoma Treated With Stereotactic Radiosurgery
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Brain Metastases, Adult
Keywords: Brain metastases
Glutamate
Stereotactic radiosurgery
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2021-03-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria (Target group)

* Adult patients carrying melanoma, breast or lung cancer BM of new diagnosis
* Patients eligible to SRS-GK treatment

Inclusion Criteria (Control group 1)

- Adult patients carrying melanoma, breast or lung cancer without BM

Inclusion Criteria (Control group 2)

* Adult patients carrying intracranial extra-axial benign tumor
* Patients eligible to SRS-GK treatment

Exclusion Criteria:

* Acute or chronic liver disease
* Severe anemia (Hb \<8g/dl)
* Pregnant or breastfeeding patient
* Pediatric patients
* Patients not able to express informed consent

Primary outcomes:
measure: Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, before SRS treatment.
timeFrame: Baseline (pre-SRS);
measure: Serum markers determination in newly diagnosed BM (lung, breast and melanoma) patients, after SRS treatment.
timeFrame: Baseline (pre-SRS) and at 3, 6 and 9 months
measure: Serum markers determination in melanoma, lung or breast cancer patients without BM.
timeFrame: Baseline
measure: Serum markers determination in patients carrying benign intracranial lesions before and after SRS treatment.
timeFrame: Baseline (pre-SRS) and at 3, 6 and 9 months
Secondary outcomes:
measure: Studying correlation of serum markers levels with MRI changes following SRS-GK
timeFrame: 3, 6 and 9 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele Scientific Institute
Study officials:
affiliation: IRCCS San Raffaele
name: Pietro Mortini, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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