Preoperative chemotherapy with paclitaxel in women with HER2-negative high-risk breast cancer

Phase 1

• Conditions: Patients with HER2-negative, early invasive unilateral breast cancer who are at risk of disease recurrence and suitable for neoadjuvant chemotherapy; MedDRA version: 20.0Level: LLTClassification code 10006283Term: Breast neoplasm malignant femaleSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003481-41-DE
• Lead Sponsor: FONDAZIONE MICHELANGELO - AVANZAMENTO DELLO STUDIO E CURA DEI TUMORI

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2013-03-28
• Last Update Posted: 4 December 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 632

Inclusion Criteria

1. Female patients aged 18 years or older
2. Histologically confirmed invasive unilateral breast cancer
3. HER2-negative disease (defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by either FISH, CISH, or other amplification tests done locally)
4. Known hormone receptor status (estrogen receptor [ER], progesterone receptor [PgR]), tumor grade and, if institutional standard permits, known Ki67 value
5. Available paraffin-embedded tumor block taken at diagnostic biopsy for central confirmation of HER2 eligibility, hormone receptor status, Ki67 value and biomarker evaluation is mandatory
6. One of the following breast cancer stages:
a. T2, T3, T4 a-d disease, triple negative (HER2, ER, PgR) regardless of Ki67 value
b. T2, T3, T4 a-d disease, ER and/or PgR positive. If Ki67 can be performed at the site, local Ki67 value must be =14%. If Ki67 is not available at the site, the tumor grade must be assessed as grade 2 or 3.
7. ECOG performance status 0 or 1
8. Written informed consent to participate in the trial (approved by the Institutional Review Board [IRB]/ Independent Ethics Committee [IEC]) obtained prior to any study specific screening procedures
9. Willing and able to comply with the protocol
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 632
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 632

Exclusion Criteria

1. Synchronous bilateral breast cancer or presence of metastatic disease (M1)
2. Surgical axillary staging procedure prior to study entry. Exceptions: 1) FNA of an axillary node is permitted for any patient, and 2) although not recommended, a pre-neoadjuvant therapy sentinel lymph node biopsy for patients with clinically negative axillary nodes is permitted
3. Pregnant or lactating women. Documentation of a negative pregnancy test must be available for premenopausal women with intact reproductive organs and for women less than one year after the last menstrual cycle
4. Women with childbearing potential unless (1) surgically sterile or (2) using adequate measures of contraception, for example abstinence, an intra-uterine device, or double barrier method of contraception
5. Treatment including radiation therapy, chemotherapy, biotherapy, and/or hormonal therapy for the currently diagnosed breast cancer prior to study entry
6. Previous investigational treatment for any condition within 4 weeks of randomization date
7. Patients on therapy with a strong CYP3A4 inhibitor
8. Previous or concomitant malignancy of any other type that could affect compliance with the protocol or interpretation of results. Patients with curatively treated basal cell carcinoma of the skin or in situ cervix cancer are generally eligible.
9. Pre-existing motor or sensory neuropathy of grade > 1 for any reason
10. Patients with a history of hypersensitivity due to drugs containing polyoxyethylene castor oil (Cremophor EL) (e.g., ciclosporin), or hardened castor oil (e.g., vitamin preparations for injection, etc.)
11. Other serious illness or medical condition including: history of documented congestive cardiac failure; angina pectoris requiring anti-anginal medication; evidence of transmural infarction on ECG; poorly controlled hypertension (e.g. systolic >180 mm Hg or diastolic >100 mm Hg; however, patients with hypertension which is well controlled on medication are eligible); clinically significant valvular heart disease; high-risk uncontrolled arrhythmias
12. Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drugs
13. Serious uncontrolled infections (bacterial or viral) or poorly controlled diabetes mellitus
14. Any of the following abnormal baseline hematological values: a. Absolute Neutrophil Count (ANC) < 1.5 x 109/L b. Platelet count < 100 x 109/L c. Hemoglobin (Hb) < 10 g/dL
15. Any of the following abnormal baseline laboratory tests a. Serum total bilirubin > 1.5 x ULN (upper limit of normal) (except for patients with clearly documented Gilbert’s syndrome) b. Alanine transaminase (ALT) or aspartate transaminase (AST) > 1.25 x ULN c. Alkaline phosphatase > 2.5 x ULN d. Serum creatinine > 1.5 x ULN
16. Baseline left ventricular ejection fraction (LVEF) < 50% by echocardiography or multi-gated scintigraphic scan (MUGA)

Study & Design

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