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

Cephalon

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: Docetaxel; Drug: Liposomal doxorubicin hydrochloride; Drug: Cyclophosphamide; Drug: Trastuzumab; Drug: Free doxorubicin hydrochloride

Study type: Interventional

Funder types: Industry

Identifiers

NCT00712881

2008-000709-12 (EudraCT Number)

C19562/2037

Details and patient eligibility

About

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.

Enrollment: 126 patients

Sex: Female

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 (Any women becoming pregnant during the study will be withdrawn from the study.)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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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126 participants in 2 patient groups

Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH)

Experimental group

Description:

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 \[6 mg/kg\]).

Treatment:

Drug: Trastuzumab

Drug: Docetaxel

Drug: Liposomal doxorubicin hydrochloride

Drug: Cyclophosphamide

Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH)

Active Comparator group

Description:

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.

Treatment:

Drug: Free doxorubicin hydrochloride

Drug: Trastuzumab

Drug: Docetaxel

Drug: Cyclophosphamide