Ignite Creation Date:
2024-05-06 @ 9:30 AM
Last Modification Date:
2024-10-26 @ 12:15 PM
Study NCT ID:
NCT02993198
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-06-03
First Post:
2016-12-02
Brief Title:
A Prospective Study of Breast Cancer Patients With Abnormal Strain Imaging
Sponsor:
Northwestern University
Organization:
Northwestern University
Study Overview
Official Title:
A Prospective Study of Early Stage Breast Cancer Patients With Abnormal Myocardial Deformation Treated With Anthracycline andor Trastuzumab and Pertuzumab-based Cancer Therapy
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
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:
None
Brief Summary:
The Cardio-Oncology program at Northwestern offers care to cancer patients who develop cardiac toxicities from chemotherapy Breast cancer patients with the tumor marker for HER2 necessitate treatment with anthracycline andor trastuzumab and pertuzumab-based chemotherapies which are known to cause cardiac toxicities Breast cancer patients will undergo a cardio-oncology echocardiogram which incorporates advanced left ventricular assessment by utilizing deformation or strain imaging during chemotherapy treatment for surveillance of cardiac toxicities The aims of this project are
1 To create a registry of both clinical and echocardiographic variables biomarkers and genetic analysis that will be used to develop a risk model to predict LV dysfunction in early stage breast cancer patients undergoing chemotherapy with anthracycline andor trastuzumab and pertuzumab-based chemotherapy regimens
2 To propose a new management algorithm for initiation of prophylactic beta-blocker therapy for early stage breast cancer patients with preclinical cardiac toxicities demonstrated by strain parameters
3 To determine if initiation of prophylactic beta-blocker therapy in patients with early cardiac toxicity can delay or prevent a drop in LV EF and the development of clinical heart failure
4 To explore serial measurements of a suite of novel biomarkers during ongoing anticancer treatment that are presumed but not yet proven to be predictive of cardiac dysfunction in women with breast cancer
5 To identify DNA biomarkers of predilection to cardiotoxicity
6 To generate hiPSC to validate markers predictive of cardiotoxicity
1 To create a registry of both clinical and echocardiographic variables biomarkers and genetic analysis that will be used to develop a risk model to predict LV dysfunction in early stage breast cancer patients undergoing chemotherapy with anthracycline andor trastuzumab and pertuzumab-based chemotherapy regimens
2 To propose a new management algorithm for initiation of prophylactic beta-blocker therapy for early stage breast cancer patients with preclinical cardiac toxicities demonstrated by strain parameters
3 To determine if initiation of prophylactic beta-blocker therapy in patients with early cardiac toxicity can delay or prevent a drop in LV EF and the development of clinical heart failure
4 To explore serial measurements of a suite of novel biomarkers during ongoing anticancer treatment that are presumed but not yet proven to be predictive of cardiac dysfunction in women with breast cancer
5 To identify DNA biomarkers of predilection to cardiotoxicity
6 To generate hiPSC to validate markers predictive of cardiotoxicity
Detailed Description:
150 patients will be prospectively consentedscreened Over the course of the study 30 patients are expected to develop abnormal strain with a normal EF 53 They will be randomized in 11 fashion to open label carvedilol vs no treatment
All consenting patients will receive a baseline echocardiogram and blood draw for biomarkers and genetic testing Patients will be followed with echocardiograms at 3 month intervals for 12 months until completion of trastuzumabpertuzumab therapy
Based on echocardiogram findings patient will fall into four study arms A B C D Patients in Arm A normal EF and normal strain and Arm D decrease in EF 10 to a value 53 will receive current standard of care treatment and will be followed in a registry arm Arms B and C will comprise of 30 patients with normal EF who develop preclinical cardiac dysfunction as defined as a change in global longitudinal strain of 15 from baseline strain or -15 absolute longitudinal strain will be prospectively assigned 11 to receive prophylactic carvedilol Arm B vs no treatment Arm C Prophylactic carvedilol will be initiated at the starting dose of 3125 mg PO BID and titrated based on blood pressure and heart rate
Patients will be seen every 3 weeks during the titration phase at their chemotherapy appointments At each visit vitals and symptoms will be assessed for dizziness and side-effects from carvedilol If patient complains of dizziness or HR 50 bpm or SBP 100 mmHg then the dose titration should stop and the dose should be reduced to the dose at the last increased increment If there is a 10 decrease in EF to a value 53 on the next echocardiogram then standard heart failure therapy will be initiated beta-blocker andor ace-inhibitors and chemotherapy will be held as per standard of care If patients require other standard of care treatments for heart failure such as diuretic therapy or aldosterone antagonists then this will also be initiated At this point these patients will be considered to have met the study endpoint However if there is an improvement or no change in strain and EF then patients will continue with cardiac surveillance with an echo at 3 month intervals Patients who have been assigned to receive prophylactic carvedilol will continue treatment for duration of chemotherapy up to 1 year Prophylactic carvedilol will be stopped at the completion of study
A biomarker substudy will be conducted on 100 patients These patients will have labs drawn every at ten time points baseline and every 6 weeks for 12 months and 1 year post-chemotherapy A separate blood draw for generation of hiPSC and DNA testing would be done for 100 patients The blood collection will coincide with the patients chemotherapy infusions with trastuzumab These biomarkers will allow for further characterization of patients at risk for developing CTRCD
A cardio-oncology echocardiogram will include standard 2D M-mode and Doppler echocardiography 2D strain imaging and 3D LV volume This data will be processed on-line or off-line within 24 hours of completion of the echocardiogram to determine randomization
All consenting patients will receive a baseline echocardiogram and blood draw for biomarkers and genetic testing Patients will be followed with echocardiograms at 3 month intervals for 12 months until completion of trastuzumabpertuzumab therapy
Based on echocardiogram findings patient will fall into four study arms A B C D Patients in Arm A normal EF and normal strain and Arm D decrease in EF 10 to a value 53 will receive current standard of care treatment and will be followed in a registry arm Arms B and C will comprise of 30 patients with normal EF who develop preclinical cardiac dysfunction as defined as a change in global longitudinal strain of 15 from baseline strain or -15 absolute longitudinal strain will be prospectively assigned 11 to receive prophylactic carvedilol Arm B vs no treatment Arm C Prophylactic carvedilol will be initiated at the starting dose of 3125 mg PO BID and titrated based on blood pressure and heart rate
Patients will be seen every 3 weeks during the titration phase at their chemotherapy appointments At each visit vitals and symptoms will be assessed for dizziness and side-effects from carvedilol If patient complains of dizziness or HR 50 bpm or SBP 100 mmHg then the dose titration should stop and the dose should be reduced to the dose at the last increased increment If there is a 10 decrease in EF to a value 53 on the next echocardiogram then standard heart failure therapy will be initiated beta-blocker andor ace-inhibitors and chemotherapy will be held as per standard of care If patients require other standard of care treatments for heart failure such as diuretic therapy or aldosterone antagonists then this will also be initiated At this point these patients will be considered to have met the study endpoint However if there is an improvement or no change in strain and EF then patients will continue with cardiac surveillance with an echo at 3 month intervals Patients who have been assigned to receive prophylactic carvedilol will continue treatment for duration of chemotherapy up to 1 year Prophylactic carvedilol will be stopped at the completion of study
A biomarker substudy will be conducted on 100 patients These patients will have labs drawn every at ten time points baseline and every 6 weeks for 12 months and 1 year post-chemotherapy A separate blood draw for generation of hiPSC and DNA testing would be done for 100 patients The blood collection will coincide with the patients chemotherapy infusions with trastuzumab These biomarkers will allow for further characterization of patients at risk for developing CTRCD
A cardio-oncology echocardiogram will include standard 2D M-mode and Doppler echocardiography 2D strain imaging and 3D LV volume This data will be processed on-line or off-line within 24 hours of completion of the echocardiogram to determine randomization
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None