HER2 Positive Breast CancerPhase 2NCT02993198
A Prospective Study of Breast Cancer Patients With Abnormal Strain Imaging
A Phase 2 study testing Carvedilol in people with HER2 Positive Breast Cancer and Cardiovascular Abnormalities, run by Northwestern University at 1 site in United States.
Trial 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 and/or trastuzumab and pertuzumab-based chemotherapies, which are known to cause cardiac… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- HER2 Positive Breast Cancer, Cardiovascular Abnormalities
- What is being tested?
- Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 134 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to Dec 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients > 18 years of age with HER2-overexpressing early stage breast cancer (Stages I - III)
- Pathology report must include HER2 expression, estrogen and progesterone receptor status
- Normal LV function (EF > 53%) on baseline echocardiogram
- NYHA functional class I-II (no symptoms, dyspnea with more than 2 blocks)
- Scheduled to receive treatment with anthracycline and/or trastuzumab and pertuzumab-based regimens
- Patients with a history of HTN, hyperlipidemia, diabetes, mild CAD, mild valvular disease are permitted
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- Patients on concomitant cardiac medications other than beta-blockers (BB) or ace-inhibitors (ACE) therapy are permitted. Other non-cardiac medications are not prohibited.
- Women of childbearing potential and sexually active men and women should use effective contraception.
- Patients must have a signed informed consent prior to registration
Who cannot join
- LV dysfunction (EF < 53%)
- New York Heart Association (NYHA) functional class III-IV (heart failure symptoms at less than 2 blocks to advanced symptoms at rest)
- NYHA Classification: I - No limitations to activity II - Slight limitation to ordinary activity, no symptoms at rest III - Marked limitation to less than ordinary activity, no symptoms at rest IV - Inability to carry out activity without symptoms, symptoms at rest
- Pre-existing cardiac disease (moderate-severe coronary artery disease, moderate-severe valvular heart disease, constrictive/restrictive cardiomyopathies)
- Metastatic breast cancer
- Patients who have ever taken BB/ACE therapy are excluded.
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- 2nd and 3rd degree AV block
- Sick sinus syndrome
- Patients with severe bradycardia (< 50 bpm) or severe hypotension (SBP < 85 mmHg)
- Severe liver dysfunction defined as Child-Turcotte-Pugh class B \& C (significant functional compromise - decompensated disease)
- Moderate-severe Asthma
- Hypersensitivity to beta-blockers
- Patients who are pregnant/lactating are not eligible
- Unwilling to consent/assent to blood donation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective Study of Early Stage Breast Cancer Patients With Abnormal Myocardial Deformation Treated With Anthracycline and/or Trastuzumab and Pertuzumab-based Cancer Therapy
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 and/or 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:
- 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 and/or trastuzumab and pertuzumab-based chemotherapy regimens.
- 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.
- 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.
- 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.
- To identify DNA biomarkers of predilection to cardiotoxicity.
- To generate hiPSC to validate markers predictive of cardiotoxicity.
Read the detailed description
150 patients will be prospectively consented/screened. Over the course of the study, 30 patients are expected to develop abnormal strain with a normal EF > 53%. They will be randomized in 1:1 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 trastuzumab/pertuzumab 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 1:1 to receive prophylactic carvedilol (Arm B) vs. no treatment (Arm C). Prophylactic carvedilol will be initiated at the starting dose of 3.125 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 and/or 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 patient's 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.
- Being tested
- Carvedilol
- Medical subject headings
- Cardiovascular Abnormalities
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
| Study group | Role | What they receive |
|---|---|---|
| Prophylactic Carvedilol | Experimental | Carvedilol 3.125 mg by mouth every 12 hours, titrated to a max dose of 25 mg by mouth every 12 hours, depending on blood pressure and heart rate, until completion of study. Receives: Drug: Carvedilol |
| No Therapy | No intervention | Standard of care monitoring without prophylactic treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Global Longitudinal Strain
Improvement or stability in strain from baseline (i.e., increase in strain or decrease by no more than 3%).
Measured: 1 year
Secondary outcomes (1)
Number of cancer treatments
Rate of cancer treatments held for decrement in EF > 10% among groups.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study startApr 2015
- Primary completionDec 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HER2 Positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 134 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nausheen Akhter, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02993198
- Sponsor's protocol ID
- STU00200675
- Status last verified
- May 2024
- First submitted
- 2 Dec 2016
- Last updated
- 3 Jun 2024
- Results posted
- No
Publications
Gong FF, Grunblatt E, Voss WB, Rangarajan V, Raissi S, Chow K, Jafari L, Patel NP, Vaitenas I, Marion M, Ramirez H, Zhao M, Andrei AC, Baldridge AS, Murtagh G, Maganti K, Rigolin VH, Akhter N. A strain-guided trial of cardioprotection in early-stage breast cancer patients on anti-HER2 therapy (PROTECT HER2). Cardiooncology. 2024 Nov 27;10(1):85. doi: 10.1186/s40959-024-00291-5.
PubMed 39605014
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Study of Early Stage Breast Cancer Patients With Abnormal Myocardial Deformation Treated With Anthracycline and/or Trastuzumab and Pertuzumab-based Cancer Therapy
- ClinicalTrials.gov ID
- NCT02993198
- Acronym / sponsor ID
- STU00200675
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 134 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 15 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 and/or 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:
- 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 and/or trastuzumab and pertuzumab-based chemotherapy regimens.
- 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.
- 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.
- 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.
- To identify DNA biomarkers of predilection to cardiotoxicity.
- To generate hiPSC to validate markers predictive of cardiotoxicity.
Detailed description
150 patients will be prospectively consented/screened. Over the course of the study, 30 patients are expected to develop abnormal strain with a normal EF > 53%. They will be randomized in 1:1 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 trastuzumab/pertuzumab 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 1:1 to receive prophylactic carvedilol (Arm B) vs. no treatment (Arm C). Prophylactic carvedilol will be initiated at the starting dose of 3.125 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 and/or 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 patient's 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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Prophylactic Carvedilol | Experimental | Drug: CarvedilolCarvedilol 3.125 mg by mouth every 12 hours, titrated to a max dose of 25 mg by mouth every 12 hours, depending on blood pressure and heart rate, until completion of study. |
| No Therapy | No intervention | –Standard of care monitoring without prophylactic treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients > 18 years of age with HER2-overexpressing early stage breast cancer (Stages I - III)
- Pathology report must include HER2 expression, estrogen and progesterone receptor status
- Normal LV function (EF > 53%) on baseline echocardiogram
- NYHA functional class I-II (no symptoms, dyspnea with more than 2 blocks)
- Scheduled to receive treatment with anthracycline and/or trastuzumab and pertuzumab-based regimens
Key exclusion criteria (14 listed)
- LV dysfunction (EF < 53%)
- New York Heart Association (NYHA) functional class III-IV (heart failure symptoms at less than 2 blocks to advanced symptoms at rest)
- Pre-existing cardiac disease (moderate-severe coronary artery disease, moderate-severe valvular heart disease, constrictive/restrictive cardiomyopathies)
- Metastatic breast cancer
- Patients who have ever taken BB/ACE therapy are excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carvedilol | Drug | Prophylactic Carvedilol |
Primary outcome
Change in Global Longitudinal Strain
Time frame: 1 year
Improvement or stability in strain from baseline (i.e., increase in strain or decrease by no more than 3%).
1 secondary outcome
Number of cancer treatments
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2024.
- Derived from this study: PubMed 39605014Gong FF, Grunblatt E, Voss WB, Rangarajan V, Raissi S, Chow K, Jafari L, Patel NP, Vaitenas I, Marion M, Ramirez H, Zhao M, Andrei AC, Baldridge AS, Murtagh G, Maganti K, Rigolin VH, Akhter N. A strain-guided trial of cardioprotection in early-stage breast cancer patients on anti-HER2 therapy (PROTECT HER2). Cardiooncology. 2024 Nov 27;10(1):85. doi: 10.1186/s40959-024-00291-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Carvedilol in people with HER2 Positive Breast Cancer and Cardiovascular Abnormalities, run by Northwestern University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Global Longitudinal Strain (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02993198, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2024.