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

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ClinicalTrials.gov Identifier: NCT02096588
Recruitment Status : Active, not recruiting
First Posted : March 26, 2014
Last Update Posted : April 24, 2018
Sponsor:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Stage I Breast Cancer Stage II Breast Cancer Stage III Breast Cancer Drug: Simvastatin Drug: Doxorubicin/cyclophosphamide Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin
Study Start Date : May 2014
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.
Drug: Simvastatin
Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily.
Other Name: Zocor

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.
Other Name: Adriamycin/Cytoxan

Active Comparator: 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.
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.
Other Name: Adriamycin/Cytoxan




Primary Outcome Measures :
  1. Change in echocardiographic Global Longitudinal Strain (GLS) [ Time Frame: 10-15 weeks ]
    To compare the absolute change in echocardiographic GLS (Global Longitudinal Strain) from baseline to 2-3 weeks after 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


Secondary Outcome Measures :
  1. Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 52 weeks ]
    To evaluate the safety and tolerability of concurrent administration of simvastatin with (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients

  2. Recurrence free survival (RFS) with concurrent simvastatin [ Time Frame: 5 years ]
    To describe the recurrence free survival (RFS) in early stage breast cancer patients treated with anthracycline-based chemotherapy with and without concurrent simvastatin



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02096588


Locations
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United States, District of Columbia
Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Maryland
Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287-0013
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Investigators
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Principal Investigator: Karen Smith, MD, MPH SKCCC at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02096588     History of Changes
Other Study ID Numbers: J13160
J13160 ( Other Identifier: SKCCC at Johns Hopkins )
NA_00091900 ( Other Identifier: JHMIRB )
First Posted: March 26, 2014    Key Record Dates
Last Update Posted: April 24, 2018
Last Verified: April 2018

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
Breast cancer
Adriamycin
Simvastatin
Statin
Echocardiogram

Additional relevant MeSH terms:
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Breast Neoplasms
Cardiotoxicity
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Pathologic Processes
Drug-Related Side Effects and Adverse Reactions
Chemically-Induced Disorders
Radiation Injuries
Wounds and Injuries
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Simvastatin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anticholesteremic Agents
Hypolipidemic Agents