Human epidermal growth factor receptor 2 (HER2)-positive Early Breast Cancer. MedDRA version: 23.0 Level: PT Classification code 10065430 Term: HER2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >= 18 years - Ability to comply with the study protocol, in the investigator’s judgment - Eastern Cooperative Oncology Group Performance Status 2 cm in diameter, or node-positive disease - HER2-positive breast cancer confirmed by a central laboratory prior to study enrollment. HER2-positive status will be determined based on pretreatment breast biopsy material - Hormone receptor status of the primary tumor, centrally confirmed - Patient agreement to undergo mastectomy or breast conserving surgery after neoadjuvant therapy - Availability of formalin-fixed, paraffin-embedded tumor tissue block for central confirmation of HER2 and hormone receptor status and additional biomarker research - Baseline left ventricular ejection fraction (LVEF) >= 55% measured by echocardiogram or multiple-gated acquisition scan - For women of childbearing potential (WOCBP) who are sexually active: agreement to remain abstinent or use one highly effective non-hormonal contraceptive method with a failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: - Stage IV breast cancer - Patients with a history of invasive breast cancer - Patients with a history of concurrent or previously treated non-breast malignancies except for appropriately treated 1) non-melanoma skin cancer and/or 2) in situ carcinomas, including cervix, colon, and skin - Patients who have received any previous systemic therapy for treatment or prevention of breast cancer, or radiation therapy for treatment of cancer - Patients who have a past history of ductal carcinoma in situ or lobular carcinoma in situ if they have received any systemic therapy for its treatment or radiation therapy to the ipsilateral breast - Patients with high-risk for breast cancer who have received chemo preventative drugs in the past are not allowed to enter the study - Patients with multi-centric breast cancer, unless all tumors are HER2-positive - Patients with bilateral breast cancer - Patients who have undergone an excisional biopsy of primary tumor and/or axillary lymph nodes - Axillary lymph node dissection prior to initiation of neoadjuvant therapy - Sentinel lymph node biopsy prior to neoadjuvant therapy - Treatment with any investigational drug within 28 days prior to randomization - Serious cardiac illness or medical conditions - Inadequate bone marrow function, renal function or impaired liver function - Current severe, uncontrolled systemic disease that may interfere with planned treatment - Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the last dose of HER2-targeted therapy - Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in and completion of the study - Known active liver disease, for example, active viral hepatitis infection, autoimmune hepatic disorders, or sclerosing cholangitis - Concurrent, serious, uncontrolled infections, or known infection with HIV - Known hypersensitivity to study drugs, excipients, and/or murine proteins - Current chronic daily treatment with corticosteroids - History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, colon, skin, and/or non-melanoma skin carcinoma. - History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease, coronary heart disease, clinically significant electrolyte abnormalities, or family history of sudden unexplained death or long QT syndrome
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate the non-inferiority of the Cycle 7 (pre-dose Cycle 8) serum pertuzumab Ctrough of pertuzumab subcutaneous (SC) within the fixed-dose combination (FDC) compared with Perjeta IV (intravenous).;Secondary Objective: • To demonstrate the non-inferiority of the Cycle 7 (pre-dose Cycle 8) serum trastuzumab Ctrough of trastuzumab SC within the FDC compared with Herceptin IV • To evaluate the efficacy of the SC FDC of pertuzumab and trastuzumab + chemotherapy compared with Perjeta IV and Herceptin IV + chemotherapy based on total pathological complete response • To evaluate the efficacy of the SC FDC of pertuzumab and trastuzumab + chemotherapy compared with Perjeta IV and Herceptin IV + chemotherapy based on invasive disease-free survival ( including and excluding second primary non-breast cancer), event free survival (including and excluding second primary non-breast cancer), distant recurrence-free interval and overall survival • To evaluate the safety of the SC FDC of pertuzumab and trastuzumab compared with Perjeta IV and Herceptin IV;Primary end point(s): 1. Serum pertuzumab Ctrough during Cycle 7 (pre-dose Cycle 8).;Timepoint(s) of evaluation of this end point: 1. Pre-dose at Cycle 8 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Serum trastuzumab Ctrough during Cycle 7 (pre-dose Cycle 8) 2. Total pathological complete response (ypT0/isypN0) 3. Invasive disease-free survival (including and excluding second primary non-breast cancer) 4. Event free survival (including and excluding second primary non-breast cancer) 5. Distant recurrence-free interval 6. Overall survival 7. Incidence and severity of adverse events and serious adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version4 (NCI CTCAE v4) 8. Laboratory test abnormalities according to NCI CTCAE v4 9. Incidence of a symptomatic ejection fraction decrease (“Heart failure”) of New York Heart Association (NYHA) Class III or IV and a drop in LVEF of at least 10-percentage points from baseline and to below 50% 10. Cardiac death 11. Incidence of an asymptomatic or mildly symptomatic left ventricular systolic dysfunction of NYHA Class II, defined as an LVEF decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of <50%;Timepoint(s) of evaluation of this end point: 1. Pre-dose at Cycle 8 2-11. Up to 5.5 years | — |
Countries
Belgium, Brazil, Czech Republic, Germany, Korea, Republic of, Mexico, Poland, Russian Federation, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F.Hoffmann-La Roche Ltd
Outcome results
None listed