Clinical trial NCT00309556: Randomized Neoadjuvant Study of Epirubicin and Docetaxel With/Without Capecitabine in Early Breast Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Keywords: Epirubicin
Docetaxel
Capecitabine
Herceptin
Breast cancer
Lead sponsor: Austrian Breast & Colorectal Cancer Study Group
Sponsor class: NETWORK
Collaborators: name: Amgen
name: Ebewe Pharma GmbH
name: Hoffmann-La Roche
name: Sanofi
First posted: 2006-04-03
Enrollment: 536
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Rate of pathological complete remissions
timeFrame: 20 weeks
Secondary outcomes:
measure: Rates of axillary lymph node involvement and breast-conserving procedures
timeFrame: 20 weeks
Other outcomes:
Locations:
city: Guessing
country: Austria
facility: Hospital Guessing
state: Burgenland
city: Oberpullendorf
country: Austria
facility: Hospital Oberpullendorf
state: Burgenland
city: Oberwart
country: Austria
facility: Hospital Oberwart
state: Burgenland
city: Klagenfurt
country: Austria
facility: State Hospital Klagenfurt
state: Carinthia
city: St. Veit a. d. Glan
country: Austria
facility: Ordination Dr. Wette
state: Carinthia
city: St. Veit a. d. Glan
country: Austria
facility: Hospital BHB St. Veit/Glan, Surgery
state: Carinthia
city: Villach
country: Austria
facility: State Hospital Villach
state: Carinthia
city: Wolfsberg
country: Austria
facility: State Hospital Wolfsberg
state: Carinthia
city: Baden bei Wien
country: Austria
facility: Hospital Baden
state: Lower Austria
city: Krems
country: Austria
facility: Hospital Krems
state: Lower Austria
city: Wiener Neustadt
country: Austria
facility: Hospital of Wiener Neustadt
state: Lower Austria
city: Graz
country: Austria
facility: Gynaegological Medical University Graz
state: Styria
city: Graz
country: Austria
facility: Medical University of Graz, Oncology
state: Styria
city: Leoben
country: Austria
facility: State Hospital Leoben
state: Styria
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
state: Tyrol
city: Kufstein
country: Austria
facility: District Hospital Kufstein
state: Tyrol
city: Kirchdorf
country: Austria
facility: State Hospital Kirchdorf
state: Upper Austria
city: Linz
country: Austria
facility: Hospital BHS Linz
state: Upper Austria
city: Linz
country: Austria
facility: General Hospital Linz
state: Upper Austria
city: Steyr
country: Austria
facility: State Hospital Steyr
state: Upper Austria
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen
state: Upper Austria
city: Rankweil
country: Austria
facility: State Hospital Feldkirch/Rankweil
state: Vorarlberg
city: Salzburg
country: Austria
facility: Paracelsus Medical University Salzburg - Oncology
city: Vienna
country: Austria
facility: Medical University Vienna, General Hospital
city: Vienna
country: Austria
facility: State Hospital Vienna-Hietzing
city: Vienna
country: Austria
facility: Hanusch Hospital
Study officials:
affiliation: Austrian Breast & Colorectal Cancer Study Group
name: Guenther Steger, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.