Ignite Creation Date:
2024-05-06 @ 8:20 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06341842
Status:
RECRUITING
Last Update Posted:
2024-04-02
First Post:
2024-03-19
Brief Title:
Potential Protective Role of SGLT-2 Inhibitors for Chemotherapy-induced Cardiotoxicity
Sponsor:
Fondazione IRCCS Policlinico San Matteo di Pavia
Organization:
Fondazione IRCCS Policlinico San Matteo di Pavia
Study Overview
Official Title:
Study Phase II Proof of Concept National Multi-centered Randomised 11 Evaluate Whether Dapagliflozin Reduces Chemotherapy Induced Cardiotoxicity in Participants With Breast Cancer Treated With Neo- Adjuvant Anthracycline-based Chemotherapy - Trastuzumab
Status:
RECRUITING
Status Verified Date:
2024-03
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:
PROTECT
Brief Summary:
The purpose of this study is to evaluate whether dapagliflozin reduces chemotherapy-induced cardiotoxicity in participants with breast cancer treated with neo-adjuvant Anthracycline-based chemotherapy - trastuzumab The study aims to describe the efficacy for dapagliflozin as compared to standard of care Participants will be recruited in participating centers where they are planning on starting neo- adjuvant ACT-based chemotherapy andor trastuzumab for stage I-III breast cancer
Detailed Description:
Anthracyclines AC are among the most widely used chemotherapeutic agents and have been shown to be effective in a wide range of tumors in particular breast cancer Their clinical effectiveness however may be thwarted by the development of cardiotoxicity that negatively affects patients outcomes and seriously limits their oncological therapeutic opportunities A subgroup of breast cancer with overexpressed human epidermal growth factor receptor type 2 HER2 associated with poor prognosis is now treated with highly effective targeted therapies such Trastuzumab Pertuzumab trastuzumab Emtansine T-DM1 Trastuzumab Deruxtecan Based on several large-scale trials of adjuvant therapy in breast cancer the rate of cardiac dysfunction ranged from 7 to 34 with HF NYHA class III or IV rates between 0 and 4 In the last twenty years several randomized and observational trials tried to study a prophylactic intervention in order to avoid drug-induced cardiotoxicity and the onset of heart failure A meta-analysis published in 2019 showed a significant but small benefit of neurohormonal therapies in reducing decline in LV systolic function among patients undergoing chemotherapy SGLT-2 inhibitors are a class of drugs primary developed as oral hypoglycemic medications for diabetic patients In several trials SGLT-2 inhibitors also known as gliflozins have reduced HF hospitalization CV mortality and all-cause mortality to a different extent suggesting a pleiotropic effect which goes beyond glycemic control since some RCTs have employed these medications in non-diabetic patients Currently there is a lack of human evidence in the role of these medications to prevent heart failure induced by chemotherapies Quagliarello et al performed a preliminary cellular studies on mouse cardiomyocytes HL-1 cell line exposed to doxorubicin alone or combined to empaglifozin In preclinical study empaglifozin increased left ventricle ejection fraction and fraction shortening compared to doxorubicin groups p 005 prevented the reduction of radial and longitudinal strain after 10 days of treatment with doxorubicin These findings provides the proof of concept for translational studies designed to reduce adverse cardiovascular outcomes in non-diabetic cancer patients treated with doxorubicin Recently Gongora et al conduct a retrospective study to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines The authors conclude that SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines Additionally SGLT2 inhibitors appeared to be safe These data support the conducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracycline
The PROTECT trial seeks primarily to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic and symptomatic CTRCD during 18 months The key secondary is to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic CTRCD during 18 months Patients will be recruited in participating centers where they are planning on starting neo- adjuvant ACT-based chemotherapy andor trastuzumab for stage I-III breast cancer The enrollment will be ongoing for 1 year until the needed number of patients are recruited
After screening for inclusion and exclusion criteria patients will be randomized using a web-based system stratified by the use of trastuzumab to Active group chemotherapy regimen plus standard of care plus dapagliflozin 10 mgdie during 18 months Control group chemotherapy regimen plus standard of care during 18 monthsDuring follow-up period if a patient develops asymptomatic or symptomatic systolic disfunction should be treated according to good clinical practice in both arms
The sample size is computed based on the primary endpoint and makes use of the data reported in the literature At 18 months we expect a cumulative incidence of CTRCD of 35 in the control arm corresponding to an event-free survival rate of 65 With 316 patients 158 per arm we will be able to elicit an increase in event-free survival in the dapaglifozin arm up to 80 hazard ratio HR 052 78 events with a power of 80 and type I error 2-tailed of 5 This sample size accounts for a 10 dropout rate and is based on the logrank test to compare event-free survivals For calculation we used the Stata command power logrank 65 80 wdprob1 power80 alpha005
The PROTECT trial seeks primarily to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic and symptomatic CTRCD during 18 months The key secondary is to assess whether the administration of dapagliflozin is associated with a lower rate of asymptomatic CTRCD during 18 months Patients will be recruited in participating centers where they are planning on starting neo- adjuvant ACT-based chemotherapy andor trastuzumab for stage I-III breast cancer The enrollment will be ongoing for 1 year until the needed number of patients are recruited
After screening for inclusion and exclusion criteria patients will be randomized using a web-based system stratified by the use of trastuzumab to Active group chemotherapy regimen plus standard of care plus dapagliflozin 10 mgdie during 18 months Control group chemotherapy regimen plus standard of care during 18 monthsDuring follow-up period if a patient develops asymptomatic or symptomatic systolic disfunction should be treated according to good clinical practice in both arms
The sample size is computed based on the primary endpoint and makes use of the data reported in the literature At 18 months we expect a cumulative incidence of CTRCD of 35 in the control arm corresponding to an event-free survival rate of 65 With 316 patients 158 per arm we will be able to elicit an increase in event-free survival in the dapaglifozin arm up to 80 hazard ratio HR 052 78 events with a power of 80 and type I error 2-tailed of 5 This sample size accounts for a 10 dropout rate and is based on the logrank test to compare event-free survivals For calculation we used the Stata command power logrank 65 80 wdprob1 power80 alpha005
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?:
False
Is an FDA AA801 Violation?:
None