Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin

NCT ID: NCT02096588

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-20
• Study Completion Date: 2023-07-26

Brief 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. 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.

Conditions

Breast Cancer; Stage I Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Simvastatin

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.

Group Type: EXPERIMENTAL

Simvastatin

Intervention Type: DRUG

Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily.

Doxorubicin/cyclophosphamide

Intervention Type: DRUG

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.

No drug

Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration.

Group Type: ACTIVE_COMPARATOR

Doxorubicin/cyclophosphamide

Intervention Type: DRUG

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.

Interventions

Simvastatin

Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily.

Intervention Type: DRUG

Doxorubicin/cyclophosphamide

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.

Intervention Type: DRUG

Other Intervention Names

Zocor; Adriamycin/Cytoxan

Eligibility Criteria

Inclusion Criteria

• 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:

• 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)

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Avon Foundation

OTHER

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen Smith, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

SKCCC at Johns Hopkins

Locations

Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

J13160

Identifier Type: OTHER

Identifier Source: secondary_id

NA_00091900

Identifier Type: OTHER

Identifier Source: secondary_id

J13160

Identifier Type: -

Identifier Source: org_study_id