Phase IIIb Study to Evaluate the Safety and Tolerability of Herceptin SC With Perjeta and Docetaxel in Patients With HER2-positive Advanced Breast Cancer

Study Overview
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Brief Summary
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This is an open-label, single-arm, multicenter, Phase IIIb study to evaluate the safety and tolerability of Herceptin SC in combination with Perjeta IV plus docetaxel in female patients with HER2-positive metastatic or locally recurrent breast cancer. Enrolled patients are to receive study medication until disease progression, unacceptable toxicity, withdrawal of consent, death, or predefined study end, whichever occurs first. The anticipated time on study treatment is approximately 24 months. The target sample size is 400.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: pertuzumab [Perjeta]
* Drug: trastuzumab [Herceptin]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally recurrent disease not amenable to curative resection. Patients with measurable and/or non-measurable disease evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 are eligible. HER2-positive disease (defined as either immunohistochemistry [IHC] 3 + or in situ hybridization [ISH] positive) as assessed by local laboratory on primary tumor or metastatic site if primary tumor not available Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Left ventricular ejection fraction (LVEF) of at least 50% Negative serum pregnancy test result at baseline and use of effective contraception as defined by the protocol Exclusion Criteria: Previous systemic non-hormonal anti-cancer therapy for the metastatic or locally recurrent disease. Note: Prior to study entry, up to two lines of hormonal therapy for metastatic or locally recurrent disease are permitted, one of which may be in combination with everolimus. Disease-free interval of less than 6 months from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of breast cancer Previous approved or investigative anti-HER2 agents as neoadjuvant or adjuvant therapy for any breast cancer treatment, except Herceptin History of persistent Grade 2 or higher hematological toxicity resulting from previous adjuvant or neoadjuvant therapy Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI), unless they have been treated and have been stable for at least 3 months and do not require ongoing corticosteroid treatment Current peripheral neuropathy of Grade 3 or greater History of other malignancy within the last 5 years prior to first dose of study drug administration, except for carcinoma in situ of the cervix or basal cell carcinoma Inadequate organ function Uncontrolled hypertension with or without medication Clinically significant cardiovascular disease History of LVEF decline to below 50% during or after prior Herceptin neo-adjuvant or adjuvant therapy Current known infection with HIV, hepatitis B virus, or hepatitis C virus Severe uncontrolled concomitant disease that would contraindicate the use of any of the investigational drugs used in this study or that would put the patient at high risk for treatment-related complications, including severe pulmonary conditions/illness Pregnant or lactating women Dyspnea at rest due to complications of advanced malignancy or other disease requiring continuous oxygen therapy History of receiving any investigational treatment within 28 days prior to first dose of study drug administration (dosing) or concurrent participation in any interventional clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Herceptin SC + Perjeta IV + docetaxel IV<br>Single arm | Drug: Docetaxel<br>* Intravenous administration according to local label/clinical practice, after Herceptin and Perjeta.<br>Drug: pertuzumab [Perjeta]<br>* Intravenous infusion every 3 weeks. First dose: 840 mg. Subsequent doses: 420 mg<br>* Other names: RO4368451;Drug: trastuzumab [Herceptin]<br>* Subcutaneous administration of 600 mg/5 mL every 3 weeks<br>* Other names: RO0452317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 24 months after the last patient has been enrolled, approximately 3.5 years | 
| Incidence and severity of adverse events Grade >/= 3, according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 |  | Up to 24 months after the last patient has been enrolled, approximately 3.5 years | 
| Incidence of cardiac events (composite outcome measure): congestive heart failure (CHF) and cardiac death |  | Up to 24 months after the last patient has been enrolled, approximately 3.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, tumor assessments according to RECIST v1.1 |  | Up to 3.5 years | 
| Overall survival |  | Up to 3.5 years | 
| Objective response rate, defined as a complete response (CR) or a partial response (PR) |  | Up to 3.5 years | 
| Incidence of anti-Herceptin, anti-rHuPH20 antibodies |  | Up to 3.5 years |