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

Phase 1

• Conditions: Therapeutic area: Diseases [C] - Cancer [C04]; early HER-2 breast cancer

• Registration Number: EUCTR2004-002030-19-AT
• Lead Sponsor: AUSTRIAN BREAST CANCER STUDY GROUP

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2005-01-03
• Last Update Posted: 17 October 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 536

Inclusion Criteria

1. Female patients with histologic proven, core-biopsied, invasive breast cancer of any clinical and/or radiological T-stage (except T4d =inflammatory breast cancer) scheduled to receive preoperative chemotherapy. Patients with bilateral breast cancer can take part in the study if both tumours are histological proven.

2. Age 18-70 years

3. WHO performance-status < 2

4. No prior or current neoplasm except for curatively treated non melanoma skin cancer, in situ carcinoma of the cervix
except curatively treated non melanoma skin cancer or in situ cervical cancer

5. No distant disease/secondary carcinoma judged clinically and at least by chest X-ray, liver-sonography, and bone scan at the time of randomisation.

6. No medical and/or cardiologic contraindication to receive an anthracyclin- and taxan-containing chemotherapy regimen. Normal cardiac function must be confirmed by LVEF (echocardiography or Muga scan). The result must be above 50 % or above the lower normal limit of the institution

7. Results of the following assessments at the time of randomisation must be available:
- anamnesis and physical examination (within 4 weeks before enrolment)
- CT of thorax (within 4 weeks before enrolment)
- CT of abdomen (within 4 weeks before enrolment)
- bilateral Mammography (within 4 weeks before enrolment)
- Laboratory requirements (within 2 weeks before enrolment):
(a) Hematology: Leukocytes * 4.0 x 109/l, Platelets * 150 x 109/l,
(b) Hepatic function : Total bilirubin < 1.5 x ULN, ASAT (SGOT) and ALAT (SGPT) < 1.25 x ULN, Alkaline phosphatases < 1 x ULN. In case of abnormal values, the liver function tests have to be repeated within 3 days before study treatment.
(c) Renal function : Creatinine < 1 x ULN
- histology
- grading
- hormone-receptor-status
- HER2 status

8. Signed and dated Informed Consent before the start of specific protocol procedures

9. If of childbearing potential, negative pregnancy test.

10a. Assessment of HER-2 receptor: Patients may have HER-2 negative or positive disease. HER-2 positive disease is defined as HER-2 over expression measured by immunohistochemistry IHC3+ and/or by HER-2 gene amplification according to fluorescent in situ hybridization (FISH) or chromogenic in-situ hybridization (CISH).
10b. Patients randomized to receive trastuzumab must have HER-2 positive disease
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 536
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 536

Exclusion Criteria

1. Stage T4d/ inflammatory breast cancer
2. Pregnant, or lactating patients; patients of childbearing potential must implement adequate contraceptive measures during study participation except hormonal methods incl. oral contraceptives, 3-month Depo-Provera shots, monthly injections, implants, contraceptive patches
3. Pre-existing motor or sensory neurotoxicity of a severity > grade 2 by WHO criteria
4. Preoperative local treatment for breast cancer (i.e. incomplete surgery, radiotherapy)
5. Prior or concurrent systemic antitumor therapy
6. Other serious illness or medical condition
(a) congestive heart failure or unstable angina pectoris even if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or high risk uncontrolled arrythmias
(b) history of significant neurologic or psychiatric disorders including psychotic disorders, dementia or seizures that would prohibit the understanding and giving of informed consent
(c) active uncontrolled infection.
(d) unstable peptic ulcer, unstable diabetes mellitus or other contraindication for the use of corticosteroids
7. Concurrent treatment with corticosteroids except as use for the prophylactic medication 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)
8. Known hypersensitivity against taxanes and/or Epirubicin and/or Fluorouracil/Capecitabine and/or trastuzumab.
9. Known deficit of dihydropyrimidine-dehydrogenase (DPD)
10. Treatment with an investigational drug within 30 days prior to study entry.
11. Legally incapacitated and/or other circumstances which make it undesirable for the subject to understand the nature, meaning and consequences of the clinical study.
12. Concurrent psychiatric illness according to ICD (alcohol addiction) at the time of study entry.
13. Patients with New Yourk Heart Association (NYHA) class = II heart disease.
14. HER-2 positive Patients with a left ventricular ejection fraction (LVEF) of <55% by echocardiography or Muga Scan.
15. Serious uncontrolled infections (bacterial odr viral) or poorly controlled diabetes mellitus.
16. Positive infraclavicular or supraclavicular lymph node.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Rate (percentage) of pathological complete remissions at the time of final surgery <br>after 6 cycles in Arm A (Epirubicin/Docetaxel/Capecitabine-containing chemotherapy)<br>vs. Arm B (Epirubicin/Docetaxel/-containing chemotherapy)<br>;Secondary Objective: Rate (percentage) of axillary lymph node involvement at the time of final surgery in Arm A vs. Arm B.<br><br>Rate (percentage) of breast-conserving procedures at the time of final surgery in Arm A vs. Arm B.<br><br>;Primary end point(s): Rate of pathological complete remissions in Arm A (Epirubicin/Docetaxel/Capecitabine-containing chemotherapy)<br>vs. Arm B (Epirubicin/Docetaxel/-containing chemotherapy)<br>;Timepoint(s) of evaluation of this end point: at the time of final surgery <br>after 6 cycles

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Rate of axillary lymph node involvement of Arm A (± trastuzumab in HER-2 positive disease) vs. Arm B (± trastuzumab in HER-2 positive disease).;Timepoint(s) of evaluation of this end point: at the time of final surgery after 6 cycles