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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00712881
• Other study ID #: C19562/2037
• Secondary ID: 2008-000709-12
• Status: Completed
• Phase: Phase 2
• Start date: October 13, 2008
• Est. completion date: September 17, 2015

Study information

• Verified date: July 2023
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 126
• Est. completion date: September 17, 2015
• Est. primary completion date: September 17, 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Liposomal doxorubicin hydrochloride
Liposomal doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.
• Cyclophosphamide
Cyclophosphamide will be administered per dose and schedule specified in the arm description.
• Trastuzumab
Trastuzumab will be administered per dose and schedule specified in the arm description.
• Free doxorubicin hydrochloride
Free doxorubicin hydrochloride will be administered per dose and schedule specified in the arm description.
• Docetaxel
Docetaxel will be administered per dose and schedule specified in the arm description.

Locations

Country	Name	City	State
Austria	Teva Investigational Site 16	Kufstein
Austria	Teva Investigational Site 15	Wien
Belgium	Teva Investigational Site 9	Brussels
Belgium	Teva Investigational Site 29	Yvoir
France	Teva Investigational Site 4	Clichy Cedex
France	Teva Investigational Site 5	Nancy
France	Teva Investigational Site 33	Reims
France	Teva Investigational Site 8	Vandoeuvre-Les-Nancy CEDEX
Germany	Teva Investigational Site 30	Aachen
Germany	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
Italy	Teva Investigational Site 20	Napoli
Italy	Teva Investigational Site 23	Roma
Italy	Teva Investigational Site 21	Verona
Spain	Teva Investigational Site 26	Barcelona
Spain	Teva Investigational Site 3	Barcelona
Spain	Teva Investigational Site 1	Lleida
Spain	Teva Investigational Site 2	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Cephalon, Inc.

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Exhibiting a Pathological Complete Response (pCR) in Breast	The pCR of breast was based upon histologic examination, as confirmed by a central panel of experts, of resected tissue .	At the end of Cycle 8 (each cycle length = 21 days)
Secondary	Percentage of Participants Who Achieved an Objective Response (Complete Response [CR] or Partial Response [PR]), as Defined by World Health Organization (WHO) Guidelines	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.	At the end of Cycle 8 (each cycle length = 21 days)
Secondary	Percentage of Participants With Class III or IV New York Health Association (NYHA) Congestive Heart Failure (CHF)	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.	Baseline up to the end of Cycle 8 (each cycle length = 21 days)
Secondary	Change From Baseline in Left Ventricular Ejection Fraction (LVEF)	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.	Baseline, up to 5 years
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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'.	Baseline up to the end of Cycle 8 (cycle length = 21 days)
Secondary	Percentage of Participants With Progression or Death	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).	Up to 5 Years after randomization
Secondary	Percentage of Participants Achieving a Pathological Complete Response (pCR) in Breast and Node	The pCR of breast and node was based upon histologic examination, as confirmed by a central panel of experts, of breast tissue resected.	At the end of Cycle 8 (each cycle length = 21 days)
Secondary	Number of Participants Undergoing Breast Conservative Surgery		At the end of Cycle 8 (each cycle length = 21 days)
Secondary	Severity of Adverse Events as Characterized by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)	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.	Up to Week 24