Locally advanced, inflammatory or early stage HER2 positive breast cancer MedDRA version: 9.1 Level: LLT Classification code 10006194 Term: Breast cancer NOS stage I MedDRA version: 9.1 Level: LLT Classification code 10006195 Term: Breast cancer NOS stage II MedDRA version: 9.1 Level: LLT Classification code 10006196 Term: Breast cancer NOS stage III MedDRA version: 9.1 Level: LLT Classification code 10021974 Term: Inflammatory breast cancer MedDRA version: 9.1 Level: LLT Classification cod
Conditions
Interventions
Product Name: Trastuzumab SC
Product Code: Ro 045-2317/F04
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Trastuzumab
CAS Number: 180288-69-1
Current Sponsor code: RO0452317
Concentr
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have signed and dated an informed consent form 2. Female 3. Age = 18 years 4. Non-metastatic primary invasive adenocarcinoma of the breast which is clinical stage I (T1, N0, M0) to IIIC (any T, N3, M0) including inflammatory and multicentric breast cancer a. with tumor size = 1 cm b. histologically confirmed c. centrally confirmed HER2 positive (IHC3+ or ISH+) in the invasive component of the primary tumor 5. At least one measurable lesion in breast or lymph nodes, according to RECIST v1.0 criteria, except for inflammatory carcinoma (T4d) 6. Performance status ECOG of 0-1 7. Baseline LVEF = 55% measured by echocardiography or MUGA scan prior to first dose of trastuzumab 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of any prior (ipsi- and/or contralateral) invasive breast carcinoma 2. Past or current history of malignant neoplasms, except for curatively treated: a. Basal and squamous cell carcinoma of the skin b. in situ carcinoma of the cervix 3. Metastatic disease 4. Any prior therapy with anthracyclines 5. Prior use of anti-HER2 therapy for any reason or other prior biologic or immunotherapy 6. Concurrent anti-cancer treatment in another investigational trial, including immunotherapy 7. Patients with severe dyspnoea at rest or requiring supplementary oxygen therapy, patients with other concurrent serious diseases that may interfere with planned treatment including severe pulmonary conditions/illness 8. Serious cardiac illness or medical conditions that would preclude the use of trastuzumab, specifically: history of documented CHF, high-risk uncontrolled arrhythmias, angina pectoris requiring medication , clinically significant valvular disease, evidence of transmural infarction on ECG, poorly controlled hypertension 9. Medical conditions that would preclude the use of 5-fluorouracil, epirubicin, cyclophosphamide or docetaxel, including: cystitis, urinary obstruction, active infections or severe mucositis 10. History of severe allergic and immunological reactions, e.g. difficult to control asthma 11. Known hypersensitivity to any of the study drugs or any of the excipients, known hypersensitivity to murine proteins 12. Known dihydropyrimidine dehydrogenase (DPD) deficiency 13. Any of the following abnormal laboratory tests at baseline: a. Biochemistry: i. serum total bilirubin > 1.25 x upper limit of normal (ULN) ii. alanine amino transferase (SGPT, ALT) or aspartate amino transferase (SGOT, AST) > 2.5 x ULN iii. alkaline phosphatase (ALP) > 2.5 x ULN iv. serum creatinine > 1.5 x ULN; b. Hematology: i. absolute neutrophil count (ANC) < 1.5 x 10e9/L ii. platelets < 100 x 10e9/L iii. haemoglobin < 10 g/dl 14. Pregnant or lactating women 15. Women of childbearing potential or less than one year after menopause (unless surgically sterile) who are unable or unwilling to use adequate contraceptive measures during study treatment 16. Patients unwilling or unable to comply with protocol procedures
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare between SC trastuzumab and IV trastuzumab in the neoadjuvant setting • the serum trough concentrations (Ctrough) observed pre-surgery • the efficacy (pathological complete response, pCR) ;Secondary Objective: To compare between SC trastuzumab and IV trastuzumab • the observed Ctrough concentrations post-surgery • the predicted Ctrough concentrations pre-surgery and post-surgery • the pharmacokinetic profile To evaluate in the SC trastuzumab and IV trastuzumab arm • total pathological complete response (tpCR) • overall response rate (ORR) • time to response (TTR) • event-free survival (EFS) • overall survival • safety and tolerability • immunogenicity (evaluation of formation of anti-trastuzumab antibodies) ;Primary end point(s): The primary efficacy variable is pathological Complete Response (pCR). This is defined as the absence of invasive neoplastic cells of the primary tumor in the breast after surgery. The primary variable for the pharmacokinetic analysis will be the observed trough concentration Ctrough of trastuzumab at cycle 7 (ie. the measured pre-dose concentration value at cycle 8). | — |
Countries
Czech Republic, Estonia, France, Germany, Hungary, Italy, Slovakia, Spain, Sweden, United Kingdom
Outcome results
None listed