Randomized Neoadjuvant Study of Epirubicin and Docetaxel With/Without Capecitabine in Early Breast Cancer

Sponsor

Austrian Breast & Colorectal Cancer Study Group (Other)

Overall Status

Completed

CT.gov ID

NCT00309556

Collaborator

Amgen (Industry), Ebewe Pharma GmbH (Other), Hoffmann-La Roche (Industry), Sanofi (Industry)

536

Enrollment

Locations

Arms

Duration (Months)

20.6

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primarily, this clinical investigation compares the rates (percentages) of pathological complete remissions attained at the time of final surgery following 6 cycles each of epirubicin + docetaxel + capecitabine-containing chemotherapy ± trastuzumab (in HER-2 positive disease) vs. epirubicin + docetaxel-containing chemotherapy ± trastuzumab (in HER-2 negative disease).

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Epirubicin Drug: Docetaxel Drug: Capecitabine Drug: Trastuzumab	Phase 3

Detailed Description

This study is a prospective, randomized, multicentre, phase III trial in the neoadjuvant treatment of patients with primary breast cancer and no distant metastases. Patients will be stratified at inclusion according to the centre, to the clinical tumour stage (T1, T2, T3, T4a-c), the axillary lymph node status (positive, negative), the menopausal status (pre-menopausal, post-menopausal), histology (invasive ductal, invasive lobular, mixed), the hormone-receptor status (positive [ER+/PR+, ER+/PR-, ER-/PR+], negative [ER-/PR-], not determinable]), the HER-2 status (positive, negative, not determinable), the grading (G1/G2, G3, not determinable) and will be randomly assigned to receive either 6 cycles of neoadjuvant epirubicin, docetaxel and capecitabine ± trastuzumab in HER-2 positive disease or 6 cycles of neoadjuvant epirubicin and docetaxel ± trastuzumab in HER-2 positive disease.

Study Design

Study Type:

Interventional

Actual Enrollment :

536 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Randomized Phase III Study Comparing Epirubicin, Docetaxel and Capecitabine + G-CSF to Epirubicin and Docetaxel + G-CSF as Neoadjuvant Treatment for Early HER-2 Negative Breast Cancer and Comparing Epirubicin, Docetaxel and Capecitabine + G-CSF ± Trastuzumab to Epirubicin and Docetaxel + G-CSF ± Trastuzumab as Neoadjuvant Treatment for Early HER-2 Positive Breast Cancer

Study Start Date :

Feb 1, 2005

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A (experimental group) Epirubicin/Docetaxel/Capecitabine-containing chemotherapy ± trastuzumab in HER-2 positive disease	Drug: Epirubicin 6 cycles 75mg/m2 i.v. day 1 q3w Drug: Docetaxel 6 cycles 75mg/m2 i.v. day 1 q3w Other Names: Taxotere Drug: Capecitabine 6 cycles 1000mg/m2 oral, day 1-14 q2d Other Names: Xeloda Drug: Trastuzumab cycle 1: 8mg/kg i.v. day 1 cycle 2-6: 6mg/kg i.v. day 1 (=6 cycles q3w) Other Names: Herceptin
Active Comparator: B (control group) Epirubicin/Docetaxel-containing chemotherapy ± trastuzumab in HER-2 positive disease	Drug: Epirubicin 6 cycles 75mg/m2 i.v. day 1 q3w Drug: Docetaxel 6 cycles 75mg/m2 i.v. day 1 q3w Other Names: Taxotere Drug: Trastuzumab cycle 1: 8mg/kg i.v. day 1 cycle 2-6: 6mg/kg i.v. day 1 (=6 cycles q3w) Other Names: Herceptin

Arm

Intervention/Treatment

Active Comparator: A (experimental group)

Epirubicin/Docetaxel/Capecitabine-containing chemotherapy ± trastuzumab in HER-2 positive disease

Drug: Epirubicin

6 cycles 75mg/m2 i.v. day 1 q3w

Drug: Docetaxel

6 cycles 75mg/m2 i.v. day 1 q3w

Other Names:

Taxotere

Drug: Capecitabine

6 cycles 1000mg/m2 oral, day 1-14 q2d

Other Names:

Xeloda

Drug: Trastuzumab

cycle 1: 8mg/kg i.v. day 1 cycle 2-6: 6mg/kg i.v. day 1 (=6 cycles q3w)

Other Names:

Herceptin

Active Comparator: B (control group)

Epirubicin/Docetaxel-containing chemotherapy ± trastuzumab in HER-2 positive disease

Drug: Epirubicin

6 cycles 75mg/m2 i.v. day 1 q3w

Drug: Docetaxel

6 cycles 75mg/m2 i.v. day 1 q3w

Other Names:

Taxotere

Drug: Trastuzumab

cycle 1: 8mg/kg i.v. day 1 cycle 2-6: 6mg/kg i.v. day 1 (=6 cycles q3w)

Other Names:

Herceptin

Outcome Measures

Primary Outcome Measures

Rate of pathological complete remissions [20 weeks]
at the time of final surgery after 6 cycles of Arm A (Epirubicin/ Docetaxel/ Capecitabine-containing chemotherapy ± Trastuzumab in HER-2 positive disease) vs. Arm B (Epirubicin/Docetaxel-containing chemotherapy ± Trastuzumab in HER-2 positive disease).

Secondary Outcome Measures

Rates of axillary lymph node involvement and breast-conserving procedures [20 weeks]
at the time of final surgery in Arm A (± trastuzumab in HER-2 positive disease) vs. Arm B (± trastuzumab in HER-2 positive disease).

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female patients with histologically proven, core-biopsied, invasive breast cancer of any clinical and/or radiological T-stage (except for T4d)
Age 18-70 years
WHO performance status ≤ 2
No prior or current neoplasm except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix
No distant disease / secondary carcinoma judged clinically and at least by chest X-ray, liver sonography, and bone scan upon randomization
No medical and/or cardiologic contraindication to receive an anthracycline- and taxane-containing chemotherapy regimen. Normal cardiac function must be confirmed by LVEF (echocardiography or Muga scan). The result must be above 50% or above the institution's ULN
Results of the following assessments at the time of randomization must be available:

chest wall CT, abdomen CT, bilateral mammography: within 4 weeks before enrolment;
laboratory requirements: within 2 weeks before enrolment
hematology: neutrophils ≥ 4.0 x 109/l, platelets ≥ 150 x 109/l, haemoglobin ≥ 13 g/dl
hepatic function: total bilirubin < 1 x ULN, ASAT (SGOT) and ALAT (SGPT) < 1x ULN, alkaline phosphatase < 1 x ULN. In case of abnormal values, liver function tests have to be repeated within 3 days before study treatment.
renal function: creatinine ≤ 1 x ULN,
histology, grading, hormone receptor status, HER-2/neu status

Signed and dated informed consent before the start of specific protocol procedures
Negative pregnancy test in the presence of childbearing potential

Exclusion Criteria:

Stage T4d / inflammatory breast cancer
Pregnant or lactating patients; patients of childbearing potential must implement adequate contraceptive measures during study participation
Pre-existing motor or sensory neurotoxicity of a severity ≥ WHO grade 2
Preoperative local treatment for breast cancer (i.e. incomplete surgery, radiotherapy)
Prior or concomitant systemic antitumor therapy
Other serious illness or medical condition

congestive heart failure or unstable angina pectoris, even if medically controlled.

Previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high-risk uncontrolled arrythmias

history of significant neurologic or psychiatric disorders, including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
active uncontrolled infection
unstable peptic ulcer, unstable diabetes mellitus or other contraindication for the use of corticosteroids

Concurrent treatment with corticosteroids except as use for the prophylactic regimen, inhalational use, treatment of acute hypersensitivity reactions, treatment of nausea/vomiting or chronic treatment (initiated > 6 months prior to study entry) at low dose (≤ 20 mg methylprednisolone or equivalent)
Known hypersensitivity against taxanes and/or epirubicin and/or fluorouracil/capecitabine
Known dihydropyrimidine-dehydrogenase (DPD) deficit
Treatment with an investigational drug within 30 days prior to study entry
Legally incapacitated and/or other circumstances which make it unfeasible for the subject to understand the nature, meaning and consequences of the clinical study
Concurrent psychiatric illness according to ICD (alcohol addiction) at the time of study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hospital Guessing	Guessing	Burgenland	Austria	7540
2	Hospital Oberpullendorf	Oberpullendorf	Burgenland	Austria	7350
3	Hospital Oberwart	Oberwart	Burgenland	Austria	7400
4	State Hospital Klagenfurt	Klagenfurt	Carinthia	Austria	9026
5	Ordination Dr. Wette	St. Veit a. d. Glan	Carinthia	Austria	9300
6	Hospital BHB St. Veit/Glan, Surgery	St. Veit a. d. Glan	Carinthia	Austria	9330
7	State Hospital Villach	Villach	Carinthia	Austria	9500
8	State Hospital Wolfsberg	Wolfsberg	Carinthia	Austria	9400
9	Hospital Baden	Baden bei Wien	Lower Austria	Austria	2500
10	Hospital Krems	Krems	Lower Austria	Austria	3500
11	Hospital of Wiener Neustadt	Wiener Neustadt	Lower Austria	Austria	2700
12	Gynaegological Medical University Graz	Graz	Styria	Austria	8036
13	Medical University of Graz, Oncology	Graz	Styria	Austria	8036
14	State Hospital Leoben	Leoben	Styria	Austria	8700
15	Medical University of Innsbruck	Innsbruck	Tyrol	Austria	6020
16	District Hospital Kufstein	Kufstein	Tyrol	Austria	6330
17	State Hospital Kirchdorf	Kirchdorf	Upper Austria	Austria	4560
18	Hospital BHS Linz	Linz	Upper Austria	Austria	4010
19	General Hospital Linz	Linz	Upper Austria	Austria	4020
20	State Hospital Steyr	Steyr	Upper Austria	Austria	4400
21	Klinikum Wels-Grieskirchen	Wels	Upper Austria	Austria	4600
22	State Hospital Feldkirch/Rankweil	Rankweil	Vorarlberg	Austria	6807
23	Paracelsus Medical University Salzburg - Oncology	Salzburg		Austria	5020
24	Medical University Vienna, General Hospital	Vienna		Austria	1090
25	State Hospital Vienna-Hietzing	Vienna		Austria	1130
26	Hanusch Hospital	Vienna		Austria	1140