Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000161527
Ethics application status
Approved
Date submitted
13/10/2014
Date registered
19/02/2015
Date last updated
19/02/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
Epirubicin/Paclitaxel/Cyclophosphamide-Methotrexate-Fluorouracil (E-T-CMF) as adjuvant chemotherapy in high-risk patients with operable breast cancer
Scientific title
High-risk patients with operable breast cancer treated with adjuvant Epirubicin/Paclitaxel/Cyclophosphamide-Methotrexate-Fluorouracil (E-T-CMF). An observational study of the prognostic role of selected biomarkers on disease free survival and overall survival (HE10/08).
Secondary ID [1] 285444 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 293210 0
Condition category
Condition code
Cancer 293480 293480 0 0
Breast

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Patients were treated with epirubicin [110 mg/m2 intravenous infusion (IV)] every 2 weeks for 3 cycles followed by 3 cycles of paclitaxel (200mg/m2 IV) every 2 weeks and 3 cycles of CMF (cyclophosphamide; 600 mg/m2 IV , methotrexate; 45 mg/m2 IV and fluorouracil; 600 mg/m2 IV) every 2 weeks.
Filgrastim was recommended in each cycle. Ondansetron + Dexamethazone was recommended as antiemetic treatment in all patients. All patients entered the study who were eligible to receive trastuzumab, received it for 1 year after the completion of chemotherapy. In these patients hormonal treatment with tamoxifen or anastrazole (orally) was started concurrently with initiation of treatment with trastuzumab. All premenopausal patients with receptor positive status received tamoxifen daily for 5 years and goserelin (zoladex) every 3 months for 2 years. All postmenopausal patients with receptor positive status will be treated with anastrazole daily for 5 years. Radiotherapy (RT) was required for all patients (pre- or post -menopausal), providing that they had either a partial mastectomy or tumor size > 5cm and /or more than 4 positive lymph nodes, irrespectively the type of surgery (conservative or radical).
The study was used as a validation study.
The aim was to observe the prognostic role of selected biomarkers on disease-free survival (DFS) and overall survival (OS) as well as the acute and long-term toxicity. Time of observation: 10 years
Intervention code [1] 290383 0
Not applicable
Comparator / control treatment
NA
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293308 0
To evaluate the prognostic role of selected biomarkers on the tiime from study entry to recurrence (disease free survival-DFS)
Timepoint [1] 293308 0
3 years. All patients will be followed at the clinic every 6 months and annually thereafter with clinical examination, CBC, complete biochemistry, serological markers, chest X- ray, bone scan (only for the first 3 years of follow-up and thereafter if clinical indicated) and mammography (annually). Since this is an adjuvant study, follow-up will be continued for the following years (until progression or death for individual patients).
Primary outcome [2] 293309 0
To evaluate the prognostic role of selected biomarkers (gene mutation identified by next generation sequencing and DFS, OS according to immunohistochemically defined subtypes) on overall survival
Timepoint [2] 293309 0
The biomarkers are collected prospectively prior to commencement of treatment.
Secondary outcome [1] 310776 0
The secondary objective is the evaluation of the acute toxicity.
Timepoint [1] 310776 0
1 month since the last administration of chemotherapy for acute toxicity.1 month since the last infusion of Trastuzumab for those patients who receive the drug. Toxicity is assessed by laboratory evaluation of hematology and biochemistry, physical examination etc.
Secondary outcome [2] 311067 0
The secondary objective is the evaluation of long-term toxicity
Timepoint [2] 311067 0
Toxicity is assessed by laboratory evaluation of hematology and biochemistry, physical examination etc. throughout the follow-up period of the patients (for up to 10 years post completion of treatment).

Eligibility
Key inclusion criteria
Histology-confirmed epithelial cancer of the mammary gland. -Pre and post menopausal patients with operable breast cancer and involved axillary lymph nodes (T 1-3 N1-2 Mo) or patients without involved axillary nodes (T1-3 N0 Mo) (i.e. those with >= 2cm or T>1cm with at least one of the following: grade 3, age < 34 years, negative hormonal status, infiltration of blood vessels or lymphatic vessels or nerves, HER-2 (receptor tyrosine kinase) overexpression, high S fraction). WBC > 4 x 109 / l, platelets > 100 x 109 / l. Serum creatinine, SGOT, SGPT, gamma-GT, serum bilirubin 1.3 mg/ml inside the normal range of the participating hospital.Performance status (WHO) 0 or 1.Age > 18 years.Previous surgical treatment: Either radical surgery or, for a partial mastectomy, a histologically confirmed safe margin and the results of the axillary node dissection available.No evidence of significant cardiac disease. No previous antitumor chemotherapy or radiation.Time from surgery 2 to 8 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
-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 (BP> 200/110 mm Hg). A normal baseline LVEF should be demonstrated by MUGA scan or ECHO. -Documented residual or metastatic disease. -Prior chemotherapy, hormonal or radiation treatment -Pregnant or in puerperium period women, or patients unwilling to follow adequate contraceptive methods during treatment period. -History of prior cancer except for curatively treated basal-cell carcinoma of the skin or in situ carcinoma of the cervix uteri. -Patients who can not fully understand and complete the inform consent form, or patients who can not follow treatment or follow up schedule.

Study design
Purpose
Duration
Selection
Timing
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
8/02/2008
Actual
8/02/2008
Date of last participant enrolment
Anticipated
Actual
22/10/2010
Date of last data collection
Anticipated
Actual
Sample size
Target
1000
Accrual to date
Final
Recruitment outside Australia
Country [1] 6396 0
Greece
State/province [1] 6396 0

Funding & Sponsors
Funding source category [1] 290058 0
Other Collaborative groups
Name [1] 290058 0
Hellenic Cooperative Oncology Group
Country [1] 290058 0
Greece
Primary sponsor type
Other Collaborative groups
Name
Hellenic Cooperative Oncology Group
Address
18, Hatzikostanti str, 11524, Athens
Country
Greece
Secondary sponsor category [1] 288747 0
None
Name [1] 288747 0
Address [1] 288747 0
Country [1] 288747 0

Ethics approval
Ethics application status
Approved

Summary
Brief summary
The HE10/08 trial was a large observational single-arm adjuvant study, with prospective collection of biological material. It was specifically designed to be used as a validation study to our previously conducted randomized trial (ACTRN12610000151033), in our continuous quest for pivotal molecular predictors of outcome or treatment effect in patients with operable breast cancer. Patients received dose-dense Epirubicin/Paclitaxel/Cyclophosphamide-Methotrexate-Fluorouracil (E-T-CMF). Granulocyte colony-stimulating factor was given prophylactically. Ondansetron + Dexamethazone was recommended as antiemetic treatment in all patients. All patients entered the study who were eligible to receive trastuzumab (HER-2 overexpression or HER-2 gene amplification), received the drug every 3 weeks for 1 year after the completion of chemotherapy. In these patients hormonal treatment with tamoxifen or anastrazole started concurrently with initiation of treatment with trastuzumab. All premenopausal patients with receptor positive status were to receive tamoxifen p.o. daily for 5 years and goserelin (zoladex) p.o. every 3 months for 2 years. All postmenopausal patients with receptor positive status were to be treated with anastrazole for 5 years. RT was required for all patients (pre- or post -menopausal), providing that they had either a partial mastectomy or tumor size > 5cm and /or more than 4 positive lymph nodes, irrespectively the type of surgery (conservative or radical).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 51898 0
Prof George Fountzilas
Address 51898 0
Hellenic Cooperative Oncology Group, 18, Hatzikostanti str, 11524 Athens
Country 51898 0
Greece
Phone 51898 0
+302106912520
Fax 51898 0
Email 51898 0
[email protected]
Contact person for public queries
Name 51899 0
Maria Moschoni
Address 51899 0
Hellenic Cooperative Oncology Group, 18, Hatzikostanti str, 11524 Athens
Country 51899 0
Greece
Phone 51899 0
+302106912520 (ext. 12)
Fax 51899 0
Email 51899 0
[email protected]
Contact person for scientific queries
Name 51900 0
George Fountzilas
Address 51900 0
Hellenic Cooperative Oncology Group, 18, Hatzikostanti str, 11524 Athens
Country 51900 0
Greece
Phone 51900 0
+302106912520
Fax 51900 0
Email 51900 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
EmbaseAssociation between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy-A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study.2022https://dx.doi.org/10.3390/cancers14225635
N.B. These documents automatically identified may not have been verified by the study sponsor.