Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12609001036202
Ethics application status
Approved
Date submitted
20/11/2009
Date registered
4/12/2009
Date last updated
11/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Epirubicin followed by Paclitaxel followed by Cyclophosphamide-Methotrexate-Fluorouracil (E-T-CMF) versus Epirubicin and Paclitaxel followed by Cyclophosphamide-Methotrexate-Fluorouracil (ET-CMF) as adjuvant chemotherapy in node positive patients with operable breast cancer. A phase III study conducted by the Hellenic Cooperative Oncology Group.
Scientific title
Epirubicin followed by Paclitaxel followed by Cyclophosphamide-Methotrexate-Fluorouracil (E-T-CMF) vs Epirubicin and Paclitaxel followed by Cyclophosphamide-Methotrexate-Fluorouracil (ET-CMF) as adjuvant chemotherapy in node positive patients with operable breast cancer.
A phase III study conducted by the Hellenic Cooperative Oncology Group.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
High risk breast cancer patients 252201 0
Condition category
Condition code
Cancer 252396 252396 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Group B will be treated with epirubicin (83mg/m2) intravenous infusions of 30-60 minutes and paclitaxel (187mg/m2) 3-hour intravenous infusion every 3 weeks for four cycles followed by 3 cycles of CMF (cyclophosphamide; 840 mg/m2, methotrexate; 57 mg/m2 and fluorouracil; 840 mg/m2) intravenous infusions of 15 minutes every 2 weeks.
Granulocyte colony stimulating factor/GCSF support will be given as follows: pegulated filgrastim on day 2 of each dose-dense cycle subcutaneously administered by nurse or filgrastim on day 3-10 subcutaneously administered by nurse. Radiation therapy (RT) is mandatory for all patients with breast-conserving surgery or for those with four or more positive lymph nodes and/or tumor size >= 5cm. Hormonal therapy (tamoxifen 20 mg/day orally) will be delivered after the completion of chemotherapy for 5 years in all hormonal receptor-positive patients. All premenopausal patients undergo ovarian suppression for 2 years.
Intervention code [1] 241553 0
Treatment: Drugs
Comparator / control treatment
Group A will be treated with epirubicin (110 mg/m2) intravenous infusions of 30-60 minutes every 2 weeks for 3 cycles followed by 3 cycles of paclitaxel (250 mg/m2) 3-hour intravenous infusion every 2 weeks and 3 cycles of CMF (cyclophosphamide; 840 mg/m2, methotrexate; 57 mg/m2 and fluorouracil; 840 mg/m2) intravenous infusions of 15 minutes every 2 weeks.
Granulocyte colony stimulating factor (GCSF) support will be given following each cycle of chemotherapy. Radiation therapy (RT) and hormonal therapy will be delivered after the completion of chemotherapy.
Control group
Active

Outcomes
Primary outcome [1] 253273 0
Time to recurrence
Timepoint [1] 253273 0
3 years from treatment initiation.
This outcome is assessed by physical examination, laboratory evaluation of hematology and biochemistry, computed tomography (CT) of thorax and abdomen and bone scan (every 6 months for the 1st year and annually since then).
Primary outcome [2] 253274 0
Overall survival
Timepoint [2] 253274 0
3 year from treatment initiation
Secondary outcome [1] 262269 0
To compare the acute and long-term toxicity caused by the two regimens.
Toxicity is assessed by laboratory evaluation of hematology and biochemistry, physical examination etc.
Timepoint [1] 262269 0
1 month since the last administration of the drug for acute toxicity and 3-5 years for long term toxicity

Eligibility
Key inclusion criteria
Histology-confirmed epithelial cancer of the mammary gland.
Pre and post menopausal patients with early breast cancer and involved axillary lymph nodes (T 1-3 N1 Mo)
White Blood Cells > 4 x 109/l, platelets > 100 x 109/l.
Serum creatinine, Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyltransferase (GGT), serum bilirubin 1.3 mg/ml inside the normal range of the participating hospital.
Performance status (World Health Organisation) 0 or 1.
Age >= 18 years
Previous surgical treatment: Either radical surgery or, for a partial mastectomy, a histologically confirmed sane margin of 2 cm or more and the results of the axillary node dissection available.
Time from surgery 2 to 4 weeks
Informed consent of the patient according to the dispositions of the Helsinki convention and its Tokyo and Venice amendments and to individual institutional policy.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Evidence of significant cardiac disease
Patients will be ineligible if they have: History of myocardial infarction within the previous 12 months or heart failure (including cardiac insufficiency controlled by digitalis and diuretics) or arrhythmias requiring medication or uncontrolled arterial hypertension (Blood Pressure> 200/110 mm Hg). A normal baseline Left Ventricular Ejection Fraction (LVEF) should be demonstrated by multiple gate acquisition (MUGA) scan or echocardiogram (ECHO)
No previous antitumor chemotherapy or radiation

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/01/2001
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
1100
Accrual to date
Final
Recruitment outside Australia
Country [1] 2333 0
Greece
State/province [1] 2333 0

Funding & Sponsors
Funding source category [1] 244019 0
Other Collaborative groups
Name [1] 244019 0
Hellenic Cooperative Oncology Group
Country [1] 244019 0
Greece
Primary sponsor type
Other Collaborative groups
Name
Hellenic Cooperative Oncology Group
Address
18, Hatzikostandi str, 11524, Athens
Country
Greece
Secondary sponsor category [1] 251370 0
None
Name [1] 251370 0
Address [1] 251370 0
Country [1] 251370 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
This is a randomized phase III trial in high-risk breast cancer patients, to further explore the impact of dose-density in the adjuvant treatment for breast cancer. Node-positive patients are randomized to sequential dose-dense epirubicin 110 mg/m2 for 3 cycles followed by paclitaxel (Taxol) 250 mg/m2 for 3 cycles, all cycles given every 2 weeks (group A/control group), or concurrent epirubicin 83 mg/m2 and paclitaxel 187 mg/m2 every 3 weeks for 4 cycles (group B/ interventional group), both followed by 3 cycles of ‘intensified’ combination chemotherapy with cyclophosphamide, methotrexate and fluorouracil (CMF). Granulocyte colony-stimulating factor was given prophylactically with the dose-dense treatments. By protocol design, dose-intensity of epirubicin and paclitaxel, the 2 most active drugs of the regimen, were double in the control group while total cumulative dose of all drugs and duration of chemotherapy period were identical in the 2 groups. Hormonal therapy and radiation therapy were given appropriately after the completion of chemotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 30512 0
Address 30512 0
Country 30512 0
Phone 30512 0
Fax 30512 0
Email 30512 0
Contact person for public queries
Name 13759 0
Eleni Papakostaki
Address 13759 0
Hellenic Cooperative Oncology Group, 18, Hatzikostandi str, 11524, Athens
Country 13759 0
Greece
Phone 13759 0
+302106912520
Fax 13759 0
+302106912713
Email 13759 0
[email protected]
Contact person for scientific queries
Name 4687 0
George Fountzilas
Address 4687 0
Hellenic Cooperative Oncology Group, 18, Hatzikostandi str, 11524, Athens
Country 4687 0
Greece
Phone 4687 0
+302106912520
Fax 4687 0
+302106912713
Email 4687 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseComparison of filgrastim and pegfilgrastim to prevent neutropenia and maintain dose intensity of adjuvant chemotherapy in patients with breast cancer.2015https://dx.doi.org/10.1007/s00520-014-2555-y
EmbaseSafety and Tolerability of Anthracycline-Containing Adjuvant Chemotherapy in Elderly High-Risk Breast Cancer Patients.2016https://dx.doi.org/10.1016/j.clbc.2015.12.001
EmbaseComparison of the ability of different clinical treatment scores to estimate prognosis in high-risk early breast cancer patients: A hellenic cooperative oncology group study.2016https://dx.doi.org/10.1371/journal.pone.0164013
EmbaseThe prognostic value of the immunohistochemical expression of phosphorylated RB and p16 proteins in association with cyclin D1 and the p53 pathway in a large cohort of patients with breast cancer treated with taxane-based adjuvant chemotherapy.2017https://dx.doi.org/10.21873/anticanres.11648
EmbaseAssociations of angiogenesis-related proteins with specific prognostic factors, breast cancer subtypes and survival outcome in early-stage breast cancer patients. A Hellenic Cooperative Oncology Group (HeCOG) trial.2018https://dx.doi.org/10.1371/journal.pone.0200302
EmbaseThe Role of CXCL13 and CXCL9 in Early Breast Cancer.2020https://dx.doi.org/10.1016/j.clbc.2019.08.008
EmbasePrognostic impact of stromal and intratumoral CD3, CD8 and FOXP3 in adjuvantly treated breast cancer: do they add information over stromal tumor-infiltrating lymphocyte density?.2020https://dx.doi.org/10.1007/s00262-020-02557-0
EmbaseAndrogen receptor and PIM1 expression in tumor tissue of patients with triple-negative breast cancer.2021https://dx.doi.org/10.21873/CGP.20249
Dimensions AIAssociation of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group2017https://doi.org/10.1186/s12967-017-1134-7
Dimensions AIEvaluation of the prognostic role of centromere 17 gain and HER2/topoisomerase II alpha gene status and protein expression in patients with breast cancer treated with anthracycline-containing adjuvant chemotherapy: pooled analysis of two Hellenic Cooperative Oncology Group (HeCOG) phase III trials2013https://doi.org/10.1186/1471-2407-13-163
Dimensions AIalphaB-crystallin is a marker of aggressive breast cancer behavior but does not independently predict for patient outcome: a combined analysis of two randomized studies2014https://doi.org/10.1186/1472-6890-14-28
Dimensions AIEvaluation of the Prognostic Value of RANK, OPG, and RANKL mRNA Expression in Early Breast Cancer Patients Treated with Anthracycline-Based Adjuvant Chemotherapy2017https://doi.org/10.1016/j.tranon.2017.05.006
Dimensions AIPrognostic Significance of ESR1 Gene Amplification, mRNA/Protein Expression and Functional Profiles in High-Risk Early Breast Cancer: A Translational Study of the Hellenic Cooperative Oncology Group (HeCOG)2013https://doi.org/10.1371/journal.pone.0070634
Dimensions AIDifferential Response of Immunohistochemically Defined Breast Cancer Subtypes to Anthracycline-Based Adjuvant Chemotherapy with or without Paclitaxel2012https://doi.org/10.1371/journal.pone.0037946
N.B. These documents automatically identified may not have been verified by the study sponsor.