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

NCT ID: NCT00309556

Last Updated: 2011-12-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 536 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2011-11-30

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).

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.

Conditions

Breast Cancer

Keywords

Epirubicin; Docetaxel; Capecitabine; Herceptin; Breast cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A (experimental group)

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

Group Type: ACTIVE_COMPARATOR

Epirubicin

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Capecitabine

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

B (control group)

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

Group Type: ACTIVE_COMPARATOR

Epirubicin

Intervention Type: DRUG

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

Docetaxel

Intervention Type: DRUG

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

Trastuzumab

Intervention Type: DRUG

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

Interventions

Epirubicin

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

Intervention Type: DRUG

Docetaxel

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

Intervention Type: DRUG

Capecitabine

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

Intervention Type: DRUG

Trastuzumab

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

Intervention Type: DRUG

Other Intervention Names

Taxotere; Xeloda; Herceptin

Eligibility Criteria

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:

1. chest wall CT, abdomen CT, bilateral mammography: within 4 weeks before enrolment;

2. laboratory requirements: within 2 weeks before enrolment

3. hematology: neutrophils ≥ 4.0 x 109/l, platelets ≥ 150 x 109/l, haemoglobin ≥ 13 g/dl

4. 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.

5. renal function: creatinine ≤ 1 x ULN,

6. 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

1. 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

2. history of significant neurologic or psychiatric disorders, including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent

3. active uncontrolled infection

4. 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

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

Ebewe Pharma GmbH

UNKNOWN

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: collaborator

Austrian Breast & Colorectal Cancer Study Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guenther Steger, MD

Role: STUDY_CHAIR

Austrian Breast & Colorectal Cancer Study Group

Locations

Hospital Guessing

Güssing, Burgenland, Austria

Hospital Oberpullendorf

Oberpullendorf, Burgenland, Austria

Hospital Oberwart

Oberwart, Burgenland, Austria

State Hospital Klagenfurt

Klagenfurt, Carinthia, Austria

Ordination Dr. Wette

Saint Veit A. D. Glan, Carinthia, Austria

Hospital BHB St. Veit/Glan, Surgery

Saint Veit A. D. Glan, Carinthia, Austria

State Hospital Villach

Villach, Carinthia, Austria

State Hospital Wolfsberg

Wolfsberg, Carinthia, Austria

Hospital Baden

Baden, Lower Austria, Austria

Hospital Krems

Krems, Lower Austria, Austria

Hospital of Wiener Neustadt

Wiener Neustadt, Lower Austria, Austria

Paracelsus Medical University Salzburg - Oncology

Salzburg, Salzburg, Austria

Gynaegological Medical University Graz

Graz, Styria, Austria

Medical University of Graz, Oncology

Graz, Styria, Austria

State Hospital Leoben

Leoben, Styria, Austria

Medical University of Innsbruck

Innsbruck, Tyrol, Austria

District Hospital Kufstein

Kufstein, Tyrol, Austria

State Hospital Kirchdorf

Kirchdorf, Upper Austria, Austria

Hospital BHS Linz

Linz, Upper Austria, Austria

General Hospital Linz

Linz, Upper Austria, Austria

State Hospital Steyr

Steyr, Upper Austria, Austria

Klinikum Wels-Grieskirchen

Wels, Upper Austria, Austria

Medical University Vienna, General Hospital

Vienna, Vienna, Austria

State Hospital Vienna-Hietzing

Vienna, Vienna, Austria

Hanusch Hospital

Vienna, Vienna, Austria

State Hospital Feldkirch/Rankweil

Rankweil, Vorarlberg, Austria

Countries

Austria

References

Hoon SN, Lau PK, White AM, Bulsara MK, Banks PD, Redfern AD. Capecitabine for hormone receptor-positive versus hormone receptor-negative breast cancer. Cochrane Database Syst Rev. 2021 May 26;5(5):CD011220. doi: 10.1002/14651858.CD011220.pub2.

Reference Type: DERIVED

PMID: 34037241 (View on PubMed)

Steger GG, Greil R, Lang A, Rudas M, Fitzal F, Mlineritsch B, Hartmann BL, Bartsch R, Melbinger E, Hubalek M, Stoeger H, Dubsky P, Ressler S, Petzer AL, Singer CF, Muss C, Jakesz R, Gampenrieder SP, Zielinski CC, Fesl C, Gnant M; Austrian Breast and Colorectal Study Group (ABCSG). Epirubicin and docetaxel with or without capecitabine as neoadjuvant treatment for early breast cancer: final results of a randomized phase III study (ABCSG-24). Ann Oncol. 2014 Feb;25(2):366-71. doi: 10.1093/annonc/mdt508. Epub 2013 Dec 16.

Reference Type: DERIVED

PMID: 24347519 (View on PubMed)

Related Links

http://www.abcsg.at

Click here for more information about this study: ABCSG-Studien closed

Other Identifiers

Ro 09-1978

Identifier Type: OTHER

Identifier Source: secondary_id

ABCSG-24

Identifier Type: -

Identifier Source: org_study_id