Ability of L-carnitine to Prevent Heart Damage in Breast Cancer Patients Receiving Anthracycline Chemotherapy

NCT00247975 | Terminated Phase 2 DMC

• 1 other identifier: CIHR #: 126541
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is very common and afflicts 1 in 9 North American women. The treatment of breast cancer often requires the use of chemotherapy including "anthracyclines". Anthracyclines can damage the heart resulting in heart failure and even death. Clinicians and researchers are continually seeking methods that will reduce the toxic effects of anthracycline treatment. L-carnitine is a substance that is produced naturally in the body and is required for normal heart function. Animal studies have suggested that L-carnitine protects the heart from the effects of anthracyclines, however this has not been verified in humans. This study will assess the potential role of L-carnitine in the prevention of anthracycline induced heart damage. The investigators will enroll 144 patients into this study. Patients will be randomly assigned to L-carnitine therapy or to standard care (no L-carnitine therapy). Patients in the L-carnitine group will receive oral and intravenous L-carnitine prior to and after their anthracycline therapy. Patients will undergo regular follow up and testing to assess heart function. The investigators believe that patients treated with L-carnitine will benefit and have fewer complications associated with anthracycline treatment.

Conditions

Heart Failure

Keywords

L-carnitine; Breast cancer; Anthracycline Cardiotoxicity; Primary prevention; Anthracycline induced cardiotoxicity; Left Ventricular Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• To compare the effects of L-carnitine therapy versus placebo on left ventricular (LV) ejection fraction (EF) as a marker of anthracycline induced cardiotoxicity

  1 year

Secondary Outcomes (7)

• To compare the effects of L-carnitine therapy versus placebo on: other potential markers of anthracycline induced cardiotoxicity such as LV volume, LV systolic and diastolic function, troponin T (TnT) and NT-pro-brain natriuretic peptide (BNP)

  1 year

• "Anthracycline-induced cardiotoxicity" and clinical cardiac outcomes

  1 year

• Serum L-carnitine levels

  4 months

• To assess: the safety of L-carnitine

  1 year

• the predictive value of serum biomarkers (TnT, BNP, and L-carnitine levels) for cardiotoxicity and cardiac outcome (ejection fraction, LV volumes, congestive heart failure, and cardiac death)

  1 year

Interventions

L-carnitine DRUG

Patients will be randomized to L-carnitine therapy or placebo. Patients in the treatment group will receive oral L-carnitine (3 grams daily) for 3 days prior to chemotherapy, 1 gram of intravenous L-carnitine (5 cc over 5 minutes, prior to chemotherapy) on the day of chemotherapy and oral L-carnitine (3 grams daily) for 3 days after chemotherapy.

Also known as: Sigma-Tau

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients must have histologically or cytologically indicated breast cancer (stages I, II, III) eligible for adjuvant anthracycline chemotherapy \[FEC100 or AC-Taxol(paclitaxel) every 21 days.
• HER2 negative or HER2 positive breast cancer by immunohistochemistry (IHC3+) and/or fluorescent in-situ hybridization.
• Eastern cooperative oncology group (ECOG) performance status = 0, 1, 2
• Age ≥ 18 years old.
• Ability to understand and the willingness to sign a written informed consent document.
• The effects of L-carnitine on the developing human fetus at the recommended therapeutic dose are unknown. For this reason, women of child-bearing potential must agree to use adequate contraception prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Patients with evidence of metastatic breast cancer.
• Resting LV ejection fraction \< 50%.
• Patients having received previous anthracycline therapy or contraindication to anthracycline.
• Patients having a contraindication to L-carnitine therapy
• Dexrazoxane therapy at the time of enrollment.
• Patients with abnormal baseline bloodwork:
• hemoglobin ≤ 100 mg/L
• platelets ≤ 100 x 10\^9/L
• white blood cells ≤ 4 x 10\^9/L
• creatinine, AST, ALT, bilirubin \> 1.5 x the upper normal limits
• Participation in another randomized clinical trial.
• Patients having significant cardiac disease (previous myocardial infarction, congestive heart failure, or hemodynamically significant valvular heart disease) that would limit compliance with study requirements.
• Patients taking medication that may affect LV function (b-blockers, amiodarone, ACE-inhibitors, calcium channel blockers, or digoxin).
• Patients with symptoms of heart failure.
• Patients unable to participate in a study requiring long term follow up.

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

MeSH Terms

Conditions

Heart Failure; Breast Neoplasms

Interventions

Carnitine

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals

Study Officials

• Benjamin JW Chow, MD, FRCPC

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

• Rob S Beanlands, MD, FRCPC

  Ottawa Heart Institute Research Corporation

  STUDY CHAIR

• Haissam Haddad, MD, FRCPC

  Ottawa Heart Institute Research Corporation

  STUDY CHAIR

• George Wells, M.Sc., PhD

  Ottawa Heart Institute Research Corporation

  STUDY CHAIR

• Susan Dent, MD, FRCPC

  Ottawa Regional Cancer Centre

  STUDY CHAIR

• Sean Hopkins, B.Sc, RPEBC

  Ottawa Regional Cancer Centre

  STUDY CHAIR

• Michele A Turek, MD, FRCPC

  Ottawa Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2005
• First Posted: November 2, 2005
• Study Start: March 1, 2006
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2011
• Last Updated: August 16, 2022

Record last verified: 2022-08

Locations

CA (1)