Breast CancerPhase 2NCT02096588
Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin
A Phase 2 study testing Simvastatin and Doxorubicin/cyclophosphamide in people with Breast Cancer and Stage I Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites in United States.
Trial summary
Doxorubicin (Adriamycin), one of the drugs commonly used for the treatment of breast cancer, is in a class of medications called anthracyclines. Anthracyclines may cause heart damage that can lead to weakening of the heart muscle. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Stage I Breast Cancer, Stage II Breast Cancer
- What is being tested?
- Simvastatin and Doxorubicin/cyclophosphamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 May 2014to 26 Jul 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Female Sex (Note: Patients may be pre-menopausal or post-menopausal)
- Age 18 years or older
- Histologically confirmed invasive breast carcinoma, stage I-III (Note: Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 status must be known. In newly diagnosed patients planning neoadjuvant treatment, a formal assessment of axillary lymph nodes is not required.)
- Planning to initiate adjuvant or neoadjuvant AC (adriamycin and cytoxan) chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2-3 weeks x 4 cycles). (Note: Participants may be planning to receive adjuvant taxane therapy after the completion of AC chemotherapy. HER2 positive patients must be planning to initiate trastuzumab therapy after AC chemotherapy.)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Normal organ function and marrow function as defined by:
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- Absolute neutrophil count (ANC) ≥ 1,000
- Platelet count ≥ 100,000
- Total bilirubin less than or equal to the upper limit of normal
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤1.5 times the upper limit of normal
- Creatinine ≤1.5 times the upper limit of normal
- Creatine kinase (CK) ≤2.5 times the upper limit of normal
- Left ventricular ejection fraction (LVEF) as assessed by baseline echocardiogram at or above the lower limit of normal
- Women of childbearing potential must agree to use adequate contraception (non-hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of participation. Should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician immediately
- Ability to understand the study regimen and the willingness to sign a written informed consent document
- Negative pregnancy test (women of childbearing potential only)
Who cannot join
- Prior anthracycline therapy
- Currently pregnant or lactating
- Currently receiving investigational agents
- Known active liver disease (cirrhosis, chronic viral hepatitis, autoimmune liver disease or other known clinically significant active liver disease)
- Known myopathy or history of rhabdomyolysis
- Uncontrolled hypothyroidism
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- History of allergic reaction or intolerance to statin treatment
- Currently receiving statin therapy or have received any statin therapy within the last 3 months
- Known history of ischemic cardiac disease (including angina requiring anti-anginal medications, myocardial infarction, coronary artery disease documented on cardiac catheterization or ischemia documented on stress test), congestive heart failure, clinically significant arrhythmia or conduction system abnormalities, clinically significant valvular disease, clinically significant pericardial effusion or EF below the lower limit of normal
- Uncontrolled inter-current illness including, but not limited to, ongoing or active serious infection, other active cardiac disease or psychiatric illness/social situations which would limit compliance with study requirements
- Inability to swallow tablets or use of a feeding tube
- Gastrointestinal disease, surgery or malabsorption that could potentially impact the absorption of the study drug
- Daily consumption of alcohol exceeding 3 standard drinks a day (defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine or 30 mL of liquor)
- Women currently taking drugs which are strong inhibitors or inducers of CYP3A4 are not eligible. These may be found at the Indiana University Clinical Pharmacology website at http://medicine.iupui.edu/clinpharm/ddis/main-table/.
- Women taking associated with a substantial risk of myopathy when co-administered with simvastatin are not eligible. These drugs are listed in the simvastatin package insert (available at: http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf).
- Women taking medications for which interaction with simvastatin may result in increased levels are not eligible. Such drugs are listed in the simvastatin package insert (available at: http://www.merck.com/product/usa/pi_circulars/z/zocor/zocor_pi.pdf).
- Any medical condition which, in the opinion of the investigator, puts the patient at risk of potentially serious complications while on study treatment
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, 21287-0013
Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
About this study
Doxorubicin (Adriamycin), one of the drugs commonly used for the treatment of breast cancer, is in a class of medications called anthracyclines. Anthracyclines may cause heart damage that can lead to weakening of the heart muscle. This heart damage may happen right away or may occur many years after the anthracycline is given
Simvastatin is an oral medication approved by the FDA to lower cholesterol. Simvastatin is in a class of medications called statins. Some research has shown that statins may prevent heart damage that can be caused by anthracyclines like Doxorubicin (Adriamycin).
Read more
The purpose of this study is to determine if taking simvastatin while receiving the chemotherapy Doxorubicin (Adriamycin) will minimize damage to the heart.
This study is for women who will be receiving the anthracycline doxorubicin (Adriamycin) as part of their breast cancer treatment.
- Being tested
- Simvastatin, Doxorubicin/cyclophosphamide
- Keywords
- Breast cancer, Adriamycin, Simvastatin, Statin, Echocardiogram
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SimvastatinDrug
Also called Zocor
Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily.
Doxorubicin/cyclophosphamideDrug
Also called Adriamycin/Cytoxan
The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin | Experimental | Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Receives: Drug: Simvastatin; Drug: Doxorubicin/cyclophosphamide |
| No drug | Active comparator | Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Receives: Drug: Doxorubicin/cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Echocardiographic Global Longitudinal Strain (GLS)
To compare the absolute change in echocardiographic GLS (Global Longitudinal Strain) from baseline (T0) to 2-3 weeks after (T2) completion of 4 cycles of (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who do and do not receive concurrent simvastatin therapy
Measured: up to 15 weeks
Secondary outcomes (2)
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Number of participants with concurrent administration of simvastatin with (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who experience adverse events as defined by NCI CTCAE v4.0.
Measured: 52 weeks
Recurrence Free Survival (RFS) With Concurrent Simvastatin
To describe the recurrence free survival (RFS) in early stage breast cancer patients treated with anthracycline-based chemotherapy with and without concurrent simvastatin
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2014 (estimated)
- Study start20 May 2014
- Primary completion25 Apr 2017
- Study completion26 Jul 2023
Why it stopped: The Principal Investigator left Johns Hopkins
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Avon Foundation
- Responsible party
- Sponsor
- Investigators
- Karen Smith, MD, MPH, Principal investigator, SKCCC at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02096588
- Sponsor's protocol ID
- J13160
- Other IDs
- J13160, NA_00091900
- Status last verified
- Jun 2024
- First submitted
- 14 Mar 2014
- Last updated
- 9 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin
- ClinicalTrials.gov ID
- NCT02096588
- Acronym / sponsor ID
- J13160
- Keywords
- Breast cancer, Adriamycin, Simvastatin, Statin, Echocardiogram
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The Principal Investigator left Johns Hopkins
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsUniversity, hospital or other
- Collaborators
- Avon Foundation
- Study start
- 20 May 2014 (actual)
- Primary completion
- 25 Apr 2017 (actual)
- Study completion
- 26 Jul 2023 (actual)
- First posted
- 26 Mar 2014 (estimated)
- Results
- Posted 26 Jun 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Doxorubicin (Adriamycin), one of the drugs commonly used for the treatment of breast cancer, is in a class of medications called anthracyclines. Anthracyclines may cause heart damage that can lead to weakening of the heart muscle. This heart damage may happen right away or may occur many years after the anthracycline is given
Simvastatin is an oral medication approved by the FDA to lower cholesterol. Simvastatin is in a class of medications called statins. Some research has shown that statins may prevent heart damage that can be caused by anthracyclines like Doxorubicin (Adriamycin).
The purpose of this study is to determine if taking simvastatin while receiving the chemotherapy Doxorubicin (Adriamycin) will minimize damage to the heart.
This study is for women who will be receiving the anthracycline doxorubicin (Adriamycin) as part of their breast cancer treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Simvastatin | Experimental | Drug: Simvastatin, Drug: Doxorubicin/cyclophosphamideSimvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. |
| No drug | Active comparator | Drug: Doxorubicin/cyclophosphamideParticipant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Female Sex (Note: Patients may be pre-menopausal or post-menopausal)
- Age 18 years or older
- Histologically confirmed invasive breast carcinoma, stage I-III (Note: Estrogen Receptor (ER), Progesterone Receptor (PR) and HER2 status must be known. In newly diagnosed patients planning neoadjuvant treatment, a formal assessment of axillary lymph nodes is not required.)
- Planning to initiate adjuvant or neoadjuvant AC (adriamycin and cytoxan) chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 2-3 weeks x 4 cycles). (Note: Participants may be planning to receive adjuvant taxane therapy after the completion of AC chemotherapy. HER2 positive patients must be planning to initiate trastuzumab therapy after AC chemotherapy.)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Key exclusion criteria (17 listed)
- Prior anthracycline therapy
- Currently pregnant or lactating
- Currently receiving investigational agents
- Known active liver disease (cirrhosis, chronic viral hepatitis, autoimmune liver disease or other known clinically significant active liver disease)
- Known myopathy or history of rhabdomyolysis
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 |
|---|---|---|
| SimvastatinAlso: ZocorSimvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. | Drug | Simvastatin |
| Doxorubicin/cyclophosphamideAlso: Adriamycin/CytoxanThe standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician. | Drug | No drug, Simvastatin |
Primary outcome
Change in Echocardiographic Global Longitudinal Strain (GLS)
Time frame: up to 15 weeks
To compare the absolute change in echocardiographic GLS (Global Longitudinal Strain) from baseline (T0) to 2-3 weeks after (T2) completion of 4 cycles of (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who do and do not receive concurrent simvastatin therapy
2 secondary outcomes
Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Time frame: 52 weeks
Recurrence Free Survival (RFS) With Concurrent Simvastatin
Time frame: 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Karen Smith, MD, MPH principal investigator
SKCCC at Johns Hopkins
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Simvastatin and Doxorubicin/cyclophosphamide in people with Breast Cancer and Stage I Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 2 sites 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 16 inclusion and 17 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: stopped early, as of the sponsor's last update on 9 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
Yes. Results are posted in the registry (first posted 26 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Echocardiographic Global Longitudinal Strain (GLS) (time frame: up to 15 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Jul 2024.