Contact information
Type
Scientific
Primary contact
Dr Benjamin Chow
ORCID ID
Contact details
University of Ottawa Heart Institute
40 Ruskin Street
Ottawa
Ontario
K1Y 4W7
Canada
+1 613 761 4044
bchow@ottawaheart.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00247975
Protocol/serial number
MCT-78520
Study information
Scientific title
Acronym
PPACC
Study hypothesis
Primary hypothesis:
Compared to placebo, L-carnitine will reduce the cytotoxic effects of epirubicin on Left Ventricular Ejection Fraction (LVEF).
Secondary hypothesis:
Compared to placebo, patients treated with L-carnitine will have:
1. Smaller increases in LV end-systolic and end-diastolic volumes
2. Lower serum Troponin T (TnT) and Brain Natriuretic Peptide (BNP) levels
3. A reduced incidence of "anthracycline-induced cardiotoxicity"
4. Higher serum L-carnitine levels
5. Similar occurrence of adverse events (breast cancer response, seizures, etc.,)
We will also test the hypothesis that TnT, BNP, serum L-carnitine levels correlate with changes in LVEF, end systolic volume, and end diastolic volume.
Ethics approval
Approval received from the Human Research Ethics Board of University of Ottawa Heart Institute (Canada) on the 7th October 2005 (ref: UOHI 2006-124).
Study design
One centre, two arm, double blind, randomised, parallel group, placebo controlled trial, with study participant, study investigator, caregiver, outcome assessor and data-analyst blinding
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Breast Cancer
Intervention
Experimental group: L-Carnitine therapy plus chemotherapy (FEC-100):
Oral L-carnitine (3 grams daily) for three days prior to chemotherapy, 1 gram of intravenous L-carnitine (5 cc over five minutes, prior to chemotherapy) on the day of chemotherapy and oral L-carnitine (3 grams daily) for three days after chemotherapy.
Control group: placebo (matching L-Carnitine therapy) plus chemotherapy (FEC-100):
Oral placebo for three days prior to chemotherapy, intravenous placebo (5 cc over five minutes, prior to chemotherapy) on the day of chemotherapy and oral placebo for three days after chemotherapy.
Contact for public queries:
Jason King
University of Ottawa Heart Institute
40 Ruskin Street
Ottawa, Ontario
Canada
K1Y 4W7
Tel: +1 613 761 9703
Fax: +1 613 761 4596
Email: jking@ottawaheart.ca
Intervention type
Drug
Phase
Not Specified
Drug names
L-Carnitine, 5-fluorouracil, epirubicin, and cyclophosphamide
Primary outcome measures
1. Change in Ejection Fraction (EF) (measure by Radionuclide Angiocardiography [RNA]) at one year, compared to the patient's own baseline. LVEF is used clinically to assess patients' eligibility for continued chemotherapy.
Secondary outcome measures
1. LV end-systolic and end-diastolic volumes (RNA)
2. LV diastolic dysfunction (Echocardiography [ECHO])
3. Serum TnT and BNP measured with each cycle of chemotherapy (immediately prior to and three days after chemotherapy)
4. Composite outcome of: cardiac death, clinical congestive heart failure, reduction in EF requiring termination of anthracycline therapy (LVEF reduction greater than or equal to 10% and LVEF less than 50%), dexrazoxane use or "anthracycline-induced cardiotoxicity"
5. Adverse events (e.g. chemotherapy efficacy, seizures, nausea, diarrhoea)
A secondary analysis of correlation of serum biomarkers (serum L-Carnitine levels, serum TnT, BNP) with surrogate markers of cardiotoxicity (LVEF, LV volumes and diastolic dysfunction) will also be performed.
Overall trial start date
01/11/2005
Overall trial end date
31/10/2008
Reason abandoned
Eligibility
Participant inclusion criteria
1. Breast cancer patients (stages I, II, III) eligible for adjuvant epirubicin chemotherapy (5-Fluorouracil, Epirubicin, and Cyclophosphamide [FEC]-100)
2. Eastern Cooperative Oncology Group (ECOG) performance status equals zero to two
3. Informed consent
Amended as of 20/04/2007:
1. Women, aged greater than or equal to 18 years
2. Breast cancer patients (stages I, II, III) eligible for adjuvant epirubicin chemotherapy (FEC100)
3. HER2 negative breast cancer by immunohistochemistry (IHC3+) and/or fluorescent in-situ hybridization
4. Eastern Cooperative Oncology Group (ECOG) performance status equal to zero to two
5. Ability to understand and the willingness to sign a written informed consent document
6. 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
Participant type
Patient
Age group
Not Specified
Gender
Not Specified
Target number of participants
128 (Amended to 144 as of 20/04/2007)
Participant exclusion criteria
1. Resting LVEF less than 50%
2. Previous anthracycline therapy or contraindication to anthracycline
3. Contraindication to L-carnitine therapy
4. Dexrazoxane therapy at the time of enrolment
5. Participation in another randomised clinical trial
6. Significant cardiac disease (previous myocardial infarction, congestive heart failure, haemodynamically significant valvular heart disease)
7. Medication that may affect LV function or symptoms of heart failure (beta-blockers, amiodarone, Angiotensin Converting Enzyme [ACE]-inhibitors, calcium channel blockers, digoxin)
8. Aged less than 18 years or inability to give informed consent
9. Evidence of metastatic breast cancer
10. Patients unable to participate in a study requiring long term follow up
11. Abnormal baseline: Complete blood count (Haemoglobin [Hb] less than 100 mg/L, Platelets [Plt] less than 100 x 10^9/L, White Blood Cells [WBC] less than 4 x 10^9/L), creatinine, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT) or bilirubin greater than 1.5 times the upper limit of normal
Amended as of 20/04/2007:
1. Resting LVEF less than 50%
2. Previous anthracycline therapy or contraindication to anthracycline
3. Contraindication to L-carnitine therapy
4. Dexrazoxane therapy at the time of enrollment
5. Participation in another randomised clinical trial
6. Significant cardiac disease (previous myocardial infarction, congestive heart failure, hemodynamically significant valvular heart disease)
7. Medication that may affect LV function or symptoms of heart failure (b-blockers, amiodarone, ACE-inhibitors, calcium channel blockers, digoxin)
8. Pregnant or lactating women
9. Evidence of metastatic breast cancer.
10. Patients unable to participate in a study requiring long term follow up
11. Abnormal baseline: Complete blood count (Hb less than 100 mg/L, Plt less than 100 x 10^9/L, WBC less than 4 x 10^9/L), Creatinine AST, ALT or Bilirubin greater than or equal to 1.5 the upper limit of normal
Recruitment start date
01/11/2005
Recruitment end date
31/10/2008
Locations
Countries of recruitment
Canada
Trial participating centre
University of Ottawa Heart Institute
Ontario
K1Y 4W7
Canada
Sponsor information
Organisation
University of Ottawa Heart Institute (Institut de cardiologie de l'Université d'Ottawa) (Canada)
Sponsor details
40 Ruskin Street
Ottawa
Ontario
K1Y 4W7
Canada
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca/ (ref: MCT-78520)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary