Ignite Creation Date:
2024-05-19 @ 5:33 PM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06418139
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-16
First Post:
2024-04-19
Brief Title:
Association of Pembrolizumab Infusion Time and Efficacy in Patients With Non-metastatic Triple-negative Breast Cancer TNBC Treated With Neoadjuvant Chemotherapy and Immunotherapy
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Etude de lEffet de lHoraire de Perfusion de limmunothérapie Sur la réponse et la toxicité Des Traitements Chez Les Patientes Atteintes de Cancer du Sein Triple négatif à Haut Risque traité Par chimiothérapie néoadjuvante et Pembrolizumab
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-04
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:
PEMCLOCK
Brief Summary:
Background Triple negative breast cancer TNBC is characterized by an aggressive biological behaviour responsible for higher risk of recurrence and shorter median survival Pembrolizumab an immune checkpoint inhibitor ICI targeting programmed death PD-1 in association to chemotherapy showed improvement of event-free survival in patients with previously untreated stage II or III TNBC and has been approved in Europe since March 2022 for this indication KEYNOTE-522 Circadian timing system controls many various biological functions in humans including xenobiotic metabolism and elimination immune functions cell cycle event and apoptosis Thus chronotherapeutic approaches have shown improved efficacy and tolerability in the treatment of different types of cancer notably in colorectal cancer Pronounced circadian rhythms in immune functions are generated by cell-autonomous molecular clocks in T and B lymphocytes macrophages neutrophils and dendritic cells Recently first evidence of the effect of timing infusion of immune checkpoint inhibitors on prognosis of patients with cancer has been reported in several retrospective trials Landre et als meta-analysis of 7 retrospective studies including 1019 patients who had metastatic cancer was presented at the American Society of Clinical Oncology ASCO meeting in 2023 An early time-of-day ICI infusions was associated with an increase overall survival HR 049 95 CI 036-069 p 00001
Objectives The aim is to analyze immunotherapy infusion timing impact on histological response toxicity and Event Free-Survival EFS in patients with TNBC treated with Neo-Adjuvant Chemotherapy NAC associated with pembroluzimab Measure of histological response is the primary objective determined by Residual Cancer Burden RCB Secondary endpoints are Event free Survival EFS calculated from the date of diagnosis to invasive local regional or metastatic relapse contralateral breast cancer or death from any cause toxicity which is assessed by recording adverse events CT-CAE v5 occurring from start of treatment to last course
Methods Data from patients with histologically proven early TNBC treated from July 2021 to May 2023 with the association of Pembrolizumab Paclitaxel Carboplatine followed with Pembrolizumab Cyclophosphamide Epirubicine according to KEYNOTE 522 study will be collected Dosing times of each Pembrolizumab and chemotherapy infusions given to consecutive patients as a neoadjuvant standard treatment associated with chemotherapy for early TNBC are retrieved from hospital records Adjuvant Pembrolizumab timing intake will be also recorded as EFS is a secondary endpoint
Statistics First median clock hour of all infusions of Pembrolizumab will be determined Then patients will be dichotomized between morning and afternoon groups using 2 cut-offs 1 median clock of all infusions of pembrolizumab morning group will include the patients who receive the majority of Pembrolizumab infusions before this median clock hour and afternoon group patients who receive the majority of Pembrolizumab infusions after this median clock hour and 2 cut-off optimizing differences of RCB between two groups
Patients characteristics toxicities tumor response and EFS will be compared
Objectives The aim is to analyze immunotherapy infusion timing impact on histological response toxicity and Event Free-Survival EFS in patients with TNBC treated with Neo-Adjuvant Chemotherapy NAC associated with pembroluzimab Measure of histological response is the primary objective determined by Residual Cancer Burden RCB Secondary endpoints are Event free Survival EFS calculated from the date of diagnosis to invasive local regional or metastatic relapse contralateral breast cancer or death from any cause toxicity which is assessed by recording adverse events CT-CAE v5 occurring from start of treatment to last course
Methods Data from patients with histologically proven early TNBC treated from July 2021 to May 2023 with the association of Pembrolizumab Paclitaxel Carboplatine followed with Pembrolizumab Cyclophosphamide Epirubicine according to KEYNOTE 522 study will be collected Dosing times of each Pembrolizumab and chemotherapy infusions given to consecutive patients as a neoadjuvant standard treatment associated with chemotherapy for early TNBC are retrieved from hospital records Adjuvant Pembrolizumab timing intake will be also recorded as EFS is a secondary endpoint
Statistics First median clock hour of all infusions of Pembrolizumab will be determined Then patients will be dichotomized between morning and afternoon groups using 2 cut-offs 1 median clock of all infusions of pembrolizumab morning group will include the patients who receive the majority of Pembrolizumab infusions before this median clock hour and afternoon group patients who receive the majority of Pembrolizumab infusions after this median clock hour and 2 cut-off optimizing differences of RCB between two groups
Patients characteristics toxicities tumor response and EFS will be compared
Detailed Description:
None
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