A Study of Pertuzumab in Combination With Herceptin and Chemotherapy in Participants With HER2-Positive Breast Cancer

Hoffmann-La Roche225 enrolled

Overview

This 3 arm study will assess the tolerability, safety and efficacy of 3 neoadjuvant treatment regimens in participants with locally advanced, inflammatory or early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Before surgery, participants will be randomized to receive either A) 6 cycles of pertuzumab plus trastuzumab (Herceptin), with 5-fluorouracil/epirubicin/cyclophosphamide (FEC) for cycles 1-3 and docetaxel for cycles 4-6, or B) FEC for cycles 1-3 followed by pertuzumab plus trastuzumab with docetaxel for cycles 4-6, or C) 6 cycles of pertuzumab plus trastuzumab with docetaxel and carboplatin. Pertuzumab will be administered at a loading dose of 840 mg intravenously (iv), then 420 mg iv 3-weekly, trastuzumab at a loading dose of 8 mg/kg iv, then 6 mg/kg iv 3-weekly, docetaxel at 75 mg/m\^2 iv, increased to 100 mg/m\^2 iv 3-weekly, and FEC and carboplatin iv 3-weekly at standard doses. Following surgery participants will receive trastuzumab 6 mg/kg iv 3-weekly for a total of 1 year, as well as adequate chemo-, radio- and hormone therapy. Anticipated time on study treatment is 4-12 months, and target sample size is 200-300.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

225

Conditions

Breast Cancer

Interventions

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * female participants, age \>/=18 years * advanced, inflammatory or early stage unilateral invasive breast cancer * HER2-positive breast cancer * baseline left ventricular ejection fraction (LVEF) \>/=55% Exclusion Criteria: * metastatic disease (Stage IV) or bilateral breast cancer * previous anticancer therapy or radiotherapy for any malignancy * other malignancy, except for carcinoma in situ of the cervix, or basal cell carcinoma * clinically relevant cardiovascular disease * current chronic treatment with corticosteroids of \>10mg methylprednisolone or equivalent

Locations (55)

Unnamed facility

Banja Luka, Bosnia and Herzegovina

Unnamed facility

Sarajevo, Bosnia and Herzegovina

Unnamed facility

Porto Alegre, Rio Grande do Sul, Brazil

Unnamed facility

São Paulo, São Paulo, Brazil

Unnamed facility

Vancouver, British Columbia, Canada

Unnamed facility

Outcomes

Primary Outcomes

Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator

Left ventricular systolic dysfunction (LVSD) as assessed by the Investigator, including Grade 3, 4 or 5 symptomatic LVSD with symptomatic cardiac events.

Time frame: From baseline up to approximately 3.5 years

Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period

Percentage of participants with LVEF measures decline of ≥ 10% from baseline and to a value of \<50% during the pre-operative (neoadjuvant) period.

Time frame: From baseline up to approximately 18 weeks

Secondary Outcomes

Efficacy: Percentage of Participants With Complete Pathological Response (pCR)

pCR is defined as the absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. pCR is evaluated after 6 cycles of treatment and surgery or following withdrawal from the study whichever occurs sooner.

Time frame: At surgery, after 18 weeks (6 cycles) of treatment

Efficacy: Clinical Response Rate

Tumor response is defined as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) and is identified as per local practice. Clinical response rate is defined as the percentage of participants who achieve a response of CR or PR at any time pre-surgery. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by mammogram or magnetic resonance imaging (MRI) and clinical breast examination (CBE), CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions.

Time frame: During each 3-week cycle of 6 total cycles: up to 18 weeks

Efficacy: Time to Clinical Response

Time to clinical response is defined as the time from the date of first dose received to the first date of assessment of clinical response. Clinical response is defined as a response of CR or PR at any time pre-surgery. Per RECIST v1.0 for target lesions and assessed by mammogram or MRI and CBE, CR is disappearance of all target lesions; PR is \>=30% decrease in the sum of the longest diameter of target lesions.

Time frame: Up to 18 weeks

Efficacy: Percentage of Participants Achieving Breast Conserving Surgery

This is the percentage of participants who achieved breast conserving surgery out of the intent-to-treat population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant (pre-operative) treatment.

Time frame: At approximately 18 weeks

Efficacy: Percentage of Participants Without an Overall Survival (OS) Event

Overall survival (OS) was defined as the time from randomization to the date of death from any cause. Participants who were alive or lost to follow-up were censored at the last known alive date. Participants with no post-baseline information were censored at the date of randomization plus one day.

Time frame: From baseline to end of study up to 5 years

Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event

The DFS was defined as the time from the first date of no disease (i.e., date of surgery) to the first documentation of progressive disease (PD) or death. PD was assessed using RECIST v1.0 and MRI and CBE. It was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Any evidence of contralateral disease in situ was not considered as PD. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be disease-free.

Time frame: From baseline to end of study up to 5 years

Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event

Progression-free survival was defined as the time from the date of randomization to the first documentation of PD or death from any cause, whichever occurred first. PD was assessed using RECIST v1.0 and MRI and CBE. It was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be free from PD. Participants without post-baseline assessments but known to be alive were censored at the time of randomization plus one day.

Time frame: From baseline to end of study up to 5 years

Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)

Percentage of participants with signs or symptoms of cardiac events.

Time frame: From Baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)

Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events

Percentage of participants with LVEF events without signs or symptoms of cardiac events.

Time frame: From baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)

Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures

Maximum decrease in LVEF measures is the change from baseline at worst treatment value. LVEF is measured as percentage.

Time frame: From baseline up to approximately 3.5 years