Condition category
Cancer
Date applied
02/04/2007
Date assigned
02/04/2007
Last edited
19/11/2009
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

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

http://www.ottawaheart.ca/UOHI/

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

Publication citations

Additional files

Editorial Notes