A phase III, randomized, open-label study to compare pharmacokinetics, efficacy and safety of subcutaneous (SC) trastuzumab with intravenous (IV) trastuzumab administered in women with HER2 positive early breast cancer (EBC) - ND

Phase 1

• Conditions: ocally advanced, inflammatory or early stage HER2 positive breast cancer; MedDRA version: 9.1Level: LLTClassification code 10006194; MedDRA version: 9.1Level: LLTClassification code 10006195; MedDRA version: 9.1Level: LLTClassification code 10006196; MedDRA version: 9.1Level: LLTClassification code 10021974

• Registration Number: EUCTR2008-007326-19-IT
• Lead Sponsor: F. Hoffmann - La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-14
• Last Update Posted: 3 April 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 552

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/multifocal breast cancer a. with tumor size >= 1 cm by ultrasound or >= 2 cm by palpation b. histologically confirmed c. centrally confirmed HER2 positive (IHC3+ or ISH+) 5. At least one measurable lesion in breast or lymph nodes (>= 1cm by ultrasound or >=2cm by palpation), 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

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: 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 Hematology: i. absolute neutrophil count (ANC) < 1.5 x 109/L ii. platelets < 100 x 109/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

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare between SC trastuzumab and IV trastuzumab in the neoadjuvant setting the serum trough concentrations (Ctrough) observed presurgery the efficacy (pathological complete response, pCR);Primary end point(s): The study has a PK variable (observed Ctrough) and an efficacy variable (pCR) as co-primary endpoints.;Secondary Objective: To compare between SC trastuzumab and IV trastuzumab the observed Ctrough concentrations post-surgery the predicted Ctrough concentrations pre-surgery and postsurgery 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 (OS) safety and tolerability immunogenicity (evaluation of formation of antitrastuzumab antibodies)