Ignite Creation Date:
2024-05-06 @ 8:07 PM
Last Modification Date:
2024-10-26 @ 3:21 PM
Study NCT ID:
NCT06261918
Status:
RECRUITING
Last Update Posted:
2024-02-15
First Post:
2024-02-08
Brief Title:
Transcriptional and Epimetabolic Profile of Breast Carcinoma With Luminal or HER2 or Locally Advanced Triple-negative Histotype in Patients WithWithout Previous Clinical History of Metabolic Syndrome
Sponsor:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Organization:
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Study Overview
Official Title:
Transcriptional and Epimetabolic Profile of Breast Carcinoma With Luminal or HER2 or Locally Advanced Triple-negative Histotype in Patients WithWithout Previous Clinical History of Metabolic Syndrome
Status:
RECRUITING
Status Verified Date:
2024-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PROMETA
Brief Summary:
This prospective pilot study of biological specimens aims to identify new prognostic and predictive biomarkers of response to standard therapy for local advanced BC as well as to identify new targets for the development of immuno- therapeutic protocols First aim is therefore to expand our knowledge to increase the response to preoperative treatment intensify treatment patterns and select patients based on clinical parameters In this regard it appears imperative to investigate yet under-investigated factors that might impair the response to standard therapy for local advanced BC including association to metabolic syndrome and analysis of tumoral and stromal features supporting a tumor microenvironment impenetrable to both drugs and immune system cells
Detailed Description:
Breast cancer BC represents the most common cancer disease among women In Italy according to the Aiom-Airtum Report Cancer Numbers 2020 there are an estimated 54976 new cases in the female population which represents 303 of all cancers Although adherence to screening programs has improved in recent years the diagnosis of locally advanced BC accounts for about 30 of new diagnoses
Neo-adjuvant therapy NCT which is the administration of chemotherapy drugs combined with biologic therapies if indicated is the gold-standard in the setting of patients with locally advanced BC 1 It allows down-staging of the primary neoplasm so that conservative rather than demolitive surgical treatment can be performed NCT also allows prognostic evaluation based on the response obtained to the treatment itself Noteworthy a large meta-analysis conducted on 11955 patients enrolled in 12 different clinical trials reported a significant correlation between obtaining a pathological complete response pathological complete response pCR ie absence of invasive disease in both breast and lymph nodes and both event-free survival EFS and overall survival OS in all tumor subtypes albeit more pronounced for HER-2 positive neoplasms EFS HR 0 39 CI 95 031-050 OS HR 034 CI 95 024-047 or triple negative EFS HR 024 CI 95 018-033 OS HR 016 CI 95 011-025 2 To date about 30 of BC patients go on to pCR following NCT 2 thus highlighting the need for further investigation to expand the proportion of these patients who may benefit from long-lasting clinical responses following such therapy The consideration of a preexisting history of metabolic syndrome might open new avenues in therapeutic and prognostic perspectives
Despite the numerous drugs currently available for the NCT classic chemotherapy CT represents the most widely used class of drugs Growing pieces of evidence show that the efficacy of CT depends not only on its ability to directly inhibit or kill malignant cells but also on features of the tumor microenvironment in term of metabolic alterations which might influence the anti-tumoral response 3 Specifically tumor cell death promoted by cytotoxic drugs causes the release of cancer-associated antigens that in turn activate and recruit immune cells within the tumor 4 A recent Italian phase 2 study the GIADA trial showed that the number of tumor-infiltrating lymphocytes is significantly associated with pCR and that anthracycline-based chemotherapy treatment results in the establishment of a more immunogenic tumor microenvironment 5 Early results show that despite an improvement in pCR a considerable number of treated individuals still do not respond or lack long-term responses 6 This evidence suggests that such combinatorial regimens often fail to neutralize all of the immunosuppressive activities that BC enacts to resist CT evade the anti-tumor immune response and progress 7 To date the identification of a system that can predict responses to NCT and the delineation of mechanisms of immunosuppressive resistance in patients with BC unresponsive to NCT remain unresolved issues
The complex network of interactions between immune cells and other components of the tumor microenvironment results in significant heterogeneity in clinical practice to the response to precision medicine therapeutic options Consequently it will be increasingly important to decipher the functional status of the metabolic status of the tumor microenvironment in each patient in order to move from standardized therapy to individualized treatment that in the future could increase survival and improve the quality of life of a greater numbers of BC patients
Neo-adjuvant therapy NCT which is the administration of chemotherapy drugs combined with biologic therapies if indicated is the gold-standard in the setting of patients with locally advanced BC 1 It allows down-staging of the primary neoplasm so that conservative rather than demolitive surgical treatment can be performed NCT also allows prognostic evaluation based on the response obtained to the treatment itself Noteworthy a large meta-analysis conducted on 11955 patients enrolled in 12 different clinical trials reported a significant correlation between obtaining a pathological complete response pathological complete response pCR ie absence of invasive disease in both breast and lymph nodes and both event-free survival EFS and overall survival OS in all tumor subtypes albeit more pronounced for HER-2 positive neoplasms EFS HR 0 39 CI 95 031-050 OS HR 034 CI 95 024-047 or triple negative EFS HR 024 CI 95 018-033 OS HR 016 CI 95 011-025 2 To date about 30 of BC patients go on to pCR following NCT 2 thus highlighting the need for further investigation to expand the proportion of these patients who may benefit from long-lasting clinical responses following such therapy The consideration of a preexisting history of metabolic syndrome might open new avenues in therapeutic and prognostic perspectives
Despite the numerous drugs currently available for the NCT classic chemotherapy CT represents the most widely used class of drugs Growing pieces of evidence show that the efficacy of CT depends not only on its ability to directly inhibit or kill malignant cells but also on features of the tumor microenvironment in term of metabolic alterations which might influence the anti-tumoral response 3 Specifically tumor cell death promoted by cytotoxic drugs causes the release of cancer-associated antigens that in turn activate and recruit immune cells within the tumor 4 A recent Italian phase 2 study the GIADA trial showed that the number of tumor-infiltrating lymphocytes is significantly associated with pCR and that anthracycline-based chemotherapy treatment results in the establishment of a more immunogenic tumor microenvironment 5 Early results show that despite an improvement in pCR a considerable number of treated individuals still do not respond or lack long-term responses 6 This evidence suggests that such combinatorial regimens often fail to neutralize all of the immunosuppressive activities that BC enacts to resist CT evade the anti-tumor immune response and progress 7 To date the identification of a system that can predict responses to NCT and the delineation of mechanisms of immunosuppressive resistance in patients with BC unresponsive to NCT remain unresolved issues
The complex network of interactions between immune cells and other components of the tumor microenvironment results in significant heterogeneity in clinical practice to the response to precision medicine therapeutic options Consequently it will be increasingly important to decipher the functional status of the metabolic status of the tumor microenvironment in each patient in order to move from standardized therapy to individualized treatment that in the future could increase survival and improve the quality of life of a greater numbers of BC patients
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None