Combination Therapy With MYOCET® (Doxorubicin HCL Liposome for Injection) in Participants With HER2-Positive Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT00712881
- Lead Sponsor
- Cephalon, Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 126
- 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
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 (Any women becoming pregnant during the study will be withdrawn from the study.)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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) Free doxorubicin hydrochloride 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. Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) Liposomal doxorubicin hydrochloride 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 \[6 mg/kg\]). Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) Docetaxel 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 \[6 mg/kg\]). Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) Cyclophosphamide 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 \[6 mg/kg\]). Doxorubicin (MYOCET) + Cyclophosphamide + Trastuzumab (MCH) and Docetaxel + Trastuzumab (TH) Trastuzumab 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 \[6 mg/kg\]). Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) Cyclophosphamide 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. Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) Trastuzumab 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. Doxorubicin (Anthracycline) + Cyclophosphamide (AC) and Docetaxel + Trastuzumab (TH) Docetaxel 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast At the end of Cycle 8 (each cycle length = 21 days) The pCR of breast was based upon histologic examination, as confirmed by a central panel of experts, of resected tissue .
- Secondary Outcome Measures
Name Time Method Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Up to Week 24 AEs were recorded and graded per the NCI CTCAE scale. The NCI CTCAE is a toxicity 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. For summaries for the toxicity grade, participants were counted once at the greatest NCI CTCAE grade.
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) CR: Disappearance of the lesions and no new lesions. In case of bone metastasis a CR is represented by the normalization of radiography or the complete sclerotic healing of lytic area.
PR: In the case of bidimensionally measurable lesions/tumors, a decrease by at least 50% of the sum of the products of the largest perpendicular diameters of each individual lesion/tumor. In the case of unidimensionally measurable lesions a decrease by at least 50% in the largest linear tumour measurement. In the case of non-measurable but evaluable lesions an appreciable change of lesions referable to disease improvement. For bone lesions partial decrease in size or recalcification of lytic areas. No lesion should have progressed and no new lesion should appear.Percentage of Participants Achieving a Pathological Complete Response (pCR) in Breast and Node At the end of Cycle 8 (each cycle length = 21 days) The pCR of breast and node was based upon histologic examination, as confirmed by a central panel of experts, of breast tissue resected.
Number of Participants Undergoing Breast Conservative Surgery At the end of Cycle 8 (each cycle length = 21 days) Percentage of Participants With Progression or Death Up to 5 Years after randomization Progression was defined as a 25% or more increase in the size of the lesion or appearance of new lesion. If the participant did not develop an event (disease progression or death), the participant was censored at the last known tumor assessment date (or last follow-up visit without progression documented).
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) Occurrence of Class III or IV (NYHA) CHF has been reported. Class III: Participants with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. Class IV: Participants with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Baseline, up to 5 years The LVEF is a fraction of blood (in percent) pumped out of the left ventricle of the heart (the main pumping chamber). LVEF was measured using multigated acquisition (MUGA) or echocardiography.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Baseline up to the end of Cycle 8 (cycle length = 21 days) An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. The TEAE was an AE that began or worsened after treatment with study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
Trial Locations
- Locations (22)
Teva Investigational Site 30
🇩🇪Aachen, Germany
Teva Investigational Site 9
🇧🇪Brussels, Belgium
Teva Investigational Site 15
🇦🇹Wien, Austria
Teva Investigational Site 4
🇫🇷Clichy Cedex, France
Teva Investigational Site 29
🇧🇪Yvoir, Belgium
Teva Investigational Site 33
🇫🇷Reims, France
Teva Investigational Site 5
🇫🇷Nancy, France
Teva Investigational Site 26
🇪🇸Barcelona, Spain
Teva Investigational Site 8
🇫🇷Vandoeuvre-Les-Nancy CEDEX, France
Teva Investigational Site 11
🇩🇪Dusseldorf, Germany
Teva Investigational Site 25
🇩🇪Dusseldorf, Germany
Teva Investigational Site 32
🇩🇪Essen, Germany
Teva Investigational Site 34
🇩🇪Lorrach, Germany
Teva Investigational Site 14
🇩🇪Munchen, Germany
Teva Investigational Site 27
🇩🇪München, Germany
Teva Investigational Site 23
🇮🇹Roma, Italy
Teva Investigational Site 20
🇮🇹Napoli, Italy
Teva Investigational Site 21
🇮🇹Verona, Italy
Teva Investigational Site 3
🇪🇸Barcelona, Spain
Teva Investigational Site 2
🇪🇸Zaragoza, Spain
Teva Investigational Site 1
🇪🇸Lleida, Spain
Teva Investigational Site 16
🇦🇹Kufstein, Austria