Clinical trial NCT06443645: Role of Sodium-glucose Linked Transporter 2 (SGLT2) and Its Inhibitor Over CARdiotoxicity Induced by Anthracyclines and Breast Cancer Tumorigenesis SCARA-B
Official title: Role of Sodium-glucose Linked Transporter 2 (SGLT2) and Its Inhibitor Over CARdiotoxicity Induced by Anthracyclines and Breast Cancer Tumorigenesis - SCARA-B
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Breast Neoplasms
Keywords: Breast cancer
Cardiotoxicities
SGLT2
Anthracyclines
Lead sponsor: Institut de cancérologie Strasbourg Europe
Sponsor class: OTHER
First posted: 2024-06-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The recruited population concerns adult patients followed for localized breast cancer and for whom treatment with anthracycline is indicated in the adjuvant or neoadjuvant situation.

Brief summary: In the context of breast cancer, in case of an indication for chemotherapy, anthracycline-based protocols make it possible to improve the overall survival of patients most at risk. The frequency of anthracycline-related cardiac toxicities (ARCT) increases with the cumulative dose of anthracyclines administered and explains, at least in part, the increased risk of cardiovascular (CV) mortality in patient populations treated for breast cancer. The numerous indications for anthracycline-based protocols have made it possible to describe ARCT, among which heart failure with reduced left ventricular ejection fraction (LVEF) remains one of the most comorbid. In addition to left ventricular dysfunction, anthracyclines have been associated with endothelial dysfunction, microvascular damage and myocardial ischemia responsible for dilated cardiomyopathy.

Different approaches have attempted to better understand and prevent these ARCT. However, apart from the notion of limit cumulative doses of anthracyclines, few of them have made it possible to screen patients at risk and prevent the onset of cardiac dysfunction. The search for biological markers (Troponin I, BNP) or ultrasound markers (Longitudinal Strain) warning of subclinical cardiac damage is still struggling to assert its interest due in particular to significant inter- and intra-observer variability. Therapeutically, ACE inhibitors and beta-blockers have shown a significant improvement in the incidence rate of LVEF reduction during adjuvant treatment of breast cancer. However, despite equivalent signals in other cancers, the studies conducted to date are insufficiently powered and the role of these treatments is limited to secondary prevention or the treatment of objective heart failure. It remains necessary to determine new biological markers that can identify patients most at risk of ARCT and thus adapt our therapeutic prevention strategies. To do this, it is first necessary to better understand the pathophysiology underlying these ARCT.

The objective of this study is to determine whether expression of the receptor among endothelium and circulating cells, SGLT2, is associated with an additional risk of presenting cardiovascular toxicity following treatment with anthracycline. If this association is demonstrated, it will then be possible to better screen and prevent these cardiovascular complications.


Eligibility criteria: Inclusion Criteria:

* Patient \> 18 years old
* Diagnosed with localized breast cancer
* Indication for first-line surgery or anthracycline-based chemotherapy.

Exclusion Criteria:

* History of chemotherapy or targeted therapy or immunotherapy administered before inclusion
* Patient currently being treated with anti-SGLT2, conversion enzyme inhibitor or ARA2
* Patient with known heart disease (ischemic, rhythmic, valvular, etc.)
* Patient with a Glomerular filtration rate \< 45 mL/min/1.73m² according to the pre-therapeutic assessment
* Patient with impaired liver function
* Patient who is pregnant or breastfeeding
* Patient with a second cancer undergoing treatment
* Patient under guardianship or curatorship, protection of justice or deprived of liberty

Primary outcomes:
measure: Evaluate the expression of SGLT2
timeFrame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
measure: Evaluate the expression of SGLT2
timeFrame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
measure: Evaluate the expression of SGLT2
timeFrame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
measure: Evaluate the expression of SGLT2
timeFrame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Secondary outcomes:
measure: Evaluate the ex vivo functional impact at the endothelial and cardiac level of exposure to patient plasma during treatment
timeFrame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
measure: Evaluate the ex vivo functional impact at the endothelial and cardiac level of exposure to patient plasma during treatment
timeFrame: At cycles 1, 2, 3, 4 and 2-3 weeks after end of treatement.
Other outcomes:
Locations:
city: Strasbourg
country: France
facility: Institut de cancérologie Strasbourg Europe
Study officials:
affiliation: Institut de cancérologie Strasbourg Europe
name: Jean-Emmanuel KURTZ
role: PRINCIPAL_INVESTIGATOR
References: