Combination Therapy With MYOCET® (Doxorubicin HCL Liposome for Injection) in Participants With HER2-Positive Breast Cancer

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of treatment with MYOCET® (doxorubicin hydrochloride) in combination with cyclophosphamide and trastuzumab, 4 cycles, followed by docetaxel plus trastuzumab, 4 cycles, in women with stage II or III breast cancer whose tumour overexpresses the human epidermal growth factor receptor 2 (HER2) gene.

Official Title
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Prospective, Open-Label, Randomized Study of Combination Therapy of MYOCET® Plus Cyclophosphamide and Trastuzumab Versus Free Doxorubicin Plus Cyclophosphamide Alone, Each Followed by Docetaxel and Trastuzumab, in Neoadjuvant Setting in Treatment-Naive Patients With HER2-Positive Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Liposomal doxorubicin hydrochloride
* Drug: Cyclophosphamide
* Drug: Trastuzumab
* Drug: Free doxorubicin hydrochloride
* Drug: Docetaxel


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Treatment-naive participants with stage II or III invasive breast cancer (proven histologically/cytologically) and with tests showing an overexpressing of HER2. Participants have at least 1 bidimensionally measurable lesion according to the World Health Organization (WHO) criteria. The participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. The participant has an LVEF of at least 55% as assessed by multigated acquisition (MUGA) scan (preferred) or echocardiography. The participant has hematology and serum chemistry laboratory test results within specific protocol-defined ranges. Women of childbearing potential must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the treatment period and for 6 months after the last administration of study drug. Main Exclusion Criteria: The participant: Has received previous cancer therapy for breast cancer. Has any history of CHF, angina pectoris, or myocardial infarction. Has uncontrolled hypertension. Has infection, peptic ulcer, or unstable diabetes mellitus. Has been treated with live virus vaccines within 8 weeks before the first administration of study drug. Has impaired hepatic or renal function. Is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.) Has used an investigational drug within one month before the screening visit. Has a known hypersensitivity to any of the study drugs or to their active ingredients. Has an inflammatory breast cancer. Has had any other malignancies within five years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer). Note: Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)<br>Participants will receive MCH (liposomal doxorubicin hydrochloride [60 milligrams {mg}/square meter {m^2}], cyclophosphamide (600 mg/m^2), and trastuzumab (8 or 6 mg/kilogram {kg}), administered as intravenous (IV) infusion on Day 1 of each of 4 consecutive 21-day cycles. For the first cycle, the loading dose of trastuzumab will be 8 mg/kg; 6 mg/kg will be used for the remaining cycles. After 4 cycles of MCH, the treatment will be changed to 4 consecutive 21-day cycles of TH (docetaxel [100 mg/m^2] and trastuzumab [6 mg/kg]). | Drug: Liposomal doxorubicin hydrochloride<br>* Liposomal doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.<br>* Other names: Myocet®;Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered per dose and schedule specified in the arm description.<br>Drug: Trastuzumab<br>* Trastuzumab will be administered per dose and schedule specified in the arm description.<br>Drug: Docetaxel<br>* Docetaxel will be administered per dose and schedule specified in the arm description.<br>|
| Active Comparator: Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH)<br>Participants will receive AC (free doxorubicin hydrochloride [60 mg/m^2] and cyclophosphamide [600 mg/m^2]), administered as IV infusion on Day 1 of each of 4 consecutive 21-day cycles. After 4 cycles of AC, the treatment will be changed to 4 consecutive 21-day cycles of TH (docetaxel [100 mg/m^2] and trastuzumab [8 or 6 mg/kg]). For the first cycle, the loading dose of trastuzumab will be 8 mg/kg; 6 mg/kg will be used for the remaining cycles. | Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered per dose and schedule specified in the arm description.<br>Drug: Trastuzumab<br>* Trastuzumab will be administered per dose and schedule specified in the arm description.<br>Drug: Free doxorubicin hydrochloride<br>* Free doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.<br>* Other names: Anthracycline;Drug: Docetaxel<br>* Docetaxel will be administered per dose and schedule specified in the arm description.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast |  | At the end of Cycle 8 (each cycle length = 21 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who Achieved an Objective Response (Complete Response [CR] or Partial Response [PR]), as Defined by World Health Organization (WHO) Guidelines |  | At the end of Cycle 8 (each cycle length = 21 days) | 
| Percentage of Participants With Class III or IV New York Health Association (NYHA) Congestive Heart Failure (CHF) |  | Baseline up to the end of Cycle 8 (each cycle length = 21 days) | 
| Change From Baseline in Left Ventricular Ejection Fraction (LVEF) |  | Baseline, up to 5 years | 
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |  | Baseline up to the end of Cycle 8 (cycle length = 21 days) | 
| Percentage of Participants Without a Progression-Free Survival (PFS) Event |  | Up to 5 Years after randomization | 
| Percentage of Participants Achieving a Pathological Complete Response (pCR) in Breast and Node |  | At the end of Cycle 8 (each cycle length = 21 days) | 
| Percentage of Participants Undergoing Breast Conservative Surgery |  | At the end of Cycle 8 (each cycle length = 21 days) | 
| Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) | The NCI CTCAE is a scale used to grade the severity of adverse events experienced with cancer treatment. Grade 1= Mild; Grade 2= Moderate; Grade 3= Severe; Grade 4= Life-threatening or disabling; Grade 5= Death related to AE. | Up to Week 24 |