A randomised, multicenter, multinational Phase II study on trastuzumab plus docetaxel versus trastuzumab plus docetaxel plus pertuzumab versus trastuzumab plus pertuzumab in patients with locally advanced, inflammatory or early stage HER2 positive breast cancer.

Conditions: ocally advanced, inflammatory or early stage HER2 positive breast cancer.
MedDRA version: 14.1Level: LLTClassification code 10065430Term: HER-2 positive breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10006200Term: Breast cancer stage IISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: PTClassification code 10006201Term: Breast cancer stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 14.1Level: LLTClassification code 10021974Term: Inflammatory breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2007-001105-13-IT

Lead Sponsor: Hoffman - La Roche

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Female

Target Recruitment: 400

Inclusion Criteria

1. Female patients ≥18 years with locally advanced, inflammatory or early stage, unilateral and histologically confirmed invasive breast cancer . 2. Primary tumor > 2cm in diameter. 3. HER2 positive confirmed by a central laboratory. Tumors must be HER2+++ by IHC or FISH/CISH + (FISH/CISH mandatory for HER2 ++ tumors). 4. Availability of FFPE tissue for central confirmation of HER2 eligibility (FFPE tumor tissue will subsequently be used for assessing status of biomarkers). 5. Age ≥ 18. 6. Baseline LVEF of ≥ 55% (measured by echocardiogram or MUGA). 7. Performance status ECOG Scale ≤ 1. 8. At least 4 weeks since major unrelated surgery, with full recovery. 9. A negative pregnancy test must be available for pre-menopausal women and for women less than 2 years after the onset of menopause. 10. Signed informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Metastatic disease (Stage IV) or bilateral breast cancer. 2. Previous anticancer therapy or radiotherapy for any malignancy. 3. Other malignancy, except for carcinoma in situ of the cervix or basal cell carcinoma. 4. Inadequate bone marrow function (e.g. Absolute Neutrophil Count (ANC) <1.5 x 1,000,000,000/L, Platelet count < 100 x 1,000,000,000/L and Hb < 9 g/dL ). 5. Impaired liver function: (e.g. serum [total] bilirubin > 1.25 x ULN (with the exception of Gilbert s syndrome), AST, ALT > 1.25 x ULN, albumin < 25 g/L 6. Inadequate renal function, serum creatinine >1.5 x ULN. 7. Uncontrolled hypertension (systolic > 150 and/or diastolic > 100), unstable angina, CHF of any NYHA classification, serious cardiac arrhythmia requiring treatment (exception, atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial. infarction within 6 months of enrollment, or LVEF < 55%. 8. Dyspnea at rest or other diseases which require continuous oxygen therapy. 9. Severe uncontrolled systemic disease (e.g. hypertension, clinically significant cardiovascular, pulmonary, metabolic, wound-healing, ulcer, or bone fracture). 10. Subjects with insulin-dependent diabetes. 11. Pregnant and/or lactating women. 12. Subjects with reproductive potential not willing to use highly effective nonhormonal method of contraception or two effective forms of non-hormonal contraception. Contraception use must continue for the duration of study treatment and for at least 6 months post discontinuation of study treatment. For details please see Section 7.2.4. 13. Received any investigational treatment within 4 weeks of study start. 14. Subjects with known infection with HIV, HBV, HCV. 15. Known hypersensitivity to any of the study drugs or excipients. 16. Subjects assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To make a preliminary assessment of the efficacy of neoadjuvant treatment of trastuzumab and docetaxel as compared to trastuzumab, pertuzumab and docetaxel as compared to trastuzumab and pertuzumab, in patients with T2-4d HER2 positive breast cancer, based on complete pathological response rate.;Secondary Objective: To evaluate the safety profiles of each treatment regimen, including pre-operative (neoadjuvant) and post-operative (adjuvant) treatment. To determine the time to clinical response, time-to-response, disease free survival and progression free survival for each treatment arm. To evaluate the biomarkers that may be associated with primary and secondary efficacy endpoints in accordance with each treatment arm. To evaluate the rate of breast conservative surgery for all patients with T2-3 tumors for whom mastectomy was planned at diagnosis.;Primary end point(s): Pathological CR in the active arms

Secondary Outcome Measures