HER2-positive, operable, locally advanced or inflammatory early breast cancer. MedDRA version: 20.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10021974 Term: Inflammatory breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - age = 18 years - Histologically confirmed invasive breast cancer with a primary tumor size of > 2 cm - HER2-positive breast cancer - Patients with multifocal tumors (more than one tumor confined to the same quadrant as the primary tumor) if all discrete lesions are sampled and centrally confirmed as HER2-positive - Stage at presentation: cT2-cT4, cN0-cN3, cM0 - Known hormone receptor status of the primary tumor - Patient agreement to undergo mastectomy or breastconserving surgery after neoadjuvant therapy - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Adequate organ function as specified per protocol - Baseline LVEF = 55% measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) - Effective contraception as defined by protocol - Documentation of Hepatitis B and Hepatitis C serologies. 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 368 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 64
Exclusion criteria
Exclusion criteria: - Stage IV (metastatic) breast cancer - Patients with a history of invasive breast cancer - Patients who have received prior anti-cancer therapy for breast cancer except those patients with a history of breast lobular carcinoma in situ (LCIS) that was surgically managed or ductal carcinoma in situ (DCIS) treated exclusively with mastectomy. In case of prior history of LCIS/DCIS, >5 years must have passed from surgery until diagnosis of current breast cancer - Patients with multicentric (multiple tumors involving more than 1 quadrant) or bilateral breast cancer - Patients who have undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes - Axillary lymph node dissection or positive sentinel lymph node prior to start of neoadjuvant therapy - History of concurrent or previous non-breast malignancies except for appropriately treated (1) non-melanoma skin cancer and (2) in situ carcinomas, including cervix, colon, and skin. A patient with previous invasive non-breast cancer is eligible provided he/she has been disease-free >/= 5 years - Treatment with any investigational drug within 28 days prior to randomization - Current National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 Grade >/= 2 peripheral neuropathy - Major surgical or significant traumatic injury within 28 days prior to randomization - Any significant concurrent medical or surgical conditions or findings that would jeopardize the patient's safety or ability to complete the study - Cardiopulmonary dysfunction as defined per protocol - Pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the pathological complete response (pCR) rate (ypT0/is, ypN0) between chemotherapy, TMZ plus pertuzumab (Arm A) and TMZ emtansine plus pertuzumab (Arm B) using local evaluation. ;Secondary Objective: • To evaluate event-free survival (EFS), invasive disease-free survival (IDFS), overall survival (OS) and rate of breast-conserving surgery across treatment arms • To evaluate cardiac, hepatic, and overall safety in each treatment arm • To study the pharmacokinetic (PK) of TMZ emtansine, total TMZ, DM1, and DM1-containing catabolites in patients with early breast cancer (EBC) receiving TMZ emtansine • To study the anti-therapeutic antibody (ATA) responses to TMZ emtansine in patients with EBC receiving TMZ emtansine • To study the PK and ATA of TMZ in patients with EBC receiving TMZ • To evaluate bothersome treatment-related symptoms of systemic chemotherapy • To assess the deterioration in global health status/health-related quality of life (HRQoL) and functional scales on the prespecified scales of the European Organization for Research and reatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 and the modified breast cancer module QLQ-BR23. ;Primary end point(s): Outcome Measure: Locally assessed pathological complete response (pCR) rate (ypT0/is, ypN0).;Timepoint(s) of evaluation of this end point: Approximately 21 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.) - Invasive disease-free survival (IDFS) - Event-free survival (EFS) - Overall survival (OS) - Breast-conserving surgery rate - Incidence of adverse events - Incidence of hepatic events - Incidence of cardiac events 2.) Health related quality of life as assessed by the European organization for research and treatment of cancer (EORTC) quality of life questionnaire (QLQ) C30/BR23. 3.) - Amount of total drug and drug catabolites in serum - Amount of anti-therapeutic antibodies.;Timepoint(s) of evaluation of this end point: 1.) Approximately 36 months 2.) Up to 36 months 3.) Up to 20 months. | — |
Countries
Belgium, Canada, France, Germany, Ireland, Korea, Republic of, Russian Federation, Spain, Taiwan, Ukraine, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed