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

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

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).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Epirubicin; Drug: Docetaxel; Drug: Capecitabine; Drug: Trastuzumab

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 Type: Interventional
• Enrollment (Actual): 536
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Paracelsus Medical University Salzburg - Oncology
  • Vienna, Austria, 1090
    • Medical University Vienna, General Hospital
  • Vienna, Austria, 1130
    • State Hospital Vienna-Hietzing
  • Vienna, Austria, 1140
    • Hanusch Hospital
  • Burgenland
    • Guessing, Burgenland, Austria, 7540
      • Hospital Guessing
    • Oberpullendorf, Burgenland, Austria, 7350
      • Hospital Oberpullendorf
    • Oberwart, Burgenland, Austria, 7400
      • Hospital Oberwart
  • Carinthia
    • Klagenfurt, Carinthia, Austria, 9026
      • State Hospital Klagenfurt
    • St. Veit a. d. Glan, Carinthia, Austria, 9300
      • Ordination Dr. Wette
    • St. Veit a. d. Glan, Carinthia, Austria, 9330
      • Hospital BHB St. Veit/Glan, Surgery
    • Villach, Carinthia, Austria, 9500
      • State Hospital Villach
    • Wolfsberg, Carinthia, Austria, 9400
      • State Hospital Wolfsberg
  • Lower Austria
    • Baden bei Wien, Lower Austria, Austria, 2500
      • Hospital Baden
    • Krems, Lower Austria, Austria, 3500
      • Hospital Krems
    • Wiener Neustadt, Lower Austria, Austria, 2700
      • Hospital of Wiener Neustadt
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University of Graz, Oncology
    • Graz, Styria, Austria, 8036
      • Gynaegological Medical University Graz
    • Leoben, Styria, Austria, 8700
      • State Hospital Leoben
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University of Innsbruck
    • Kufstein, Tyrol, Austria, 6330
      • District Hospital Kufstein
  • Upper Austria
    • Kirchdorf, Upper Austria, Austria, 4560
      • State Hospital Kirchdorf
    • Linz, Upper Austria, Austria, 4020
      • General Hospital Linz
    • Linz, Upper Austria, Austria, 4010
      • Hospital BHS Linz
    • Steyr, Upper Austria, Austria, 4400
      • State Hospital Steyr
    • Wels, Upper Austria, Austria, 4600
      • Klinikum Wels-Grieskirchen
  • Vorarlberg
    • Rankweil, Vorarlberg, Austria, 6807
      • State Hospital Feldkirch/Rankweil

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pathological complete remissions	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).	20 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Austrian Breast & Colorectal Cancer Study Group
• Collaborators: Sanofi; Hoffmann-La Roche; Amgen; Ebewe Pharma GmbH
• Investigators: Study Chair: Guenther Steger, MD, Austrian Breast & Colorectal Cancer Study Group

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: March 31, 2006
• First Submitted That Met QC Criteria: March 31, 2006
• First Posted (Estimate): April 3, 2006

Study Record Updates

• Last Update Posted (Estimate): December 30, 2011
• Last Update Submitted That Met QC Criteria: December 29, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: Docetaxel; Capecitabine; Breast cancer; Epirubicin; Herceptin
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Docetaxel; Trastuzumab; Capecitabine; Epirubicin
• Other Study ID Numbers: ABCSG-24; Ro 09-1978 (Other Identifier: Roche Study ID)