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-Naïve Patients With HER2-Positive Breast Cancer

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2008-000709-12-GB
• Date of registration: 15/07/2008
• Prospective Registration: Yes
• Primary sponsor: Cephalon France
• Public 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-Naïve Patients With HER2-Positive Breast Cancer
• Scientific 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-Naïve Patients With HER2-Positive Breast Cancer
• Date of first enrolment: 20/02/2009
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-000709-12
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, France, Italy, Netherlands, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are included in the study if all of the following criteria are met:
(a) Treatment-naïve patients have stage II or III invasive breast cancer histologically/cytologically proven and overexpressing human epidermal growth factor reeptor 2 (HER2) as demonstrated by fluorescence in situ hybridization (FISH) highly preferable or by SISH or by CISH.
(b) Patients have at least 1 bidimensionally measurable lesion according to the WHO criteria.
(c) The patient is a woman 18 to 70 years of age, inclusive.
(d) Written informed consent is obtained.
(e) The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
(f) The patient has an LVEF of at least 55% as assessed by multiple-gated acquisition (MUGA) scan (preferred) or echocardiography.
(g) The patient has haematology and serum chemistry laboratory test results within the following ranges:
• at least 2x10^9 neutrophils/L
• at least 100x10^9 platelets/L
• total bilirubin serum concentrations not exceeding the normal laboratory reference range
• aspartate aminotransferase (AST) serum levels not exceeding 2.5 times the upper limit of normal (ULN)
• alanine aminotransferase (ALT) serum levels not exceeding 2.5xULN
• alkaline phosphatase (ALP) serum levels not exceeding 5.0xULN
• serum creatinine serum levels not exceeding 1.5xULN
(h) Women of childbearing potential (not surgically sterile or 2 years postmenopausal) 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. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
(i) The patient must be willing and able to comply with study assessments and willing to return to the clinic for further treatment and follow-up as specified in this protocol.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients are excluded from participating in this study if 1 or more of the following criteria are met:
(a) The patient has received previous cancer therapy for breast cancer.
(b) The patient has any history of coronary heart failure (CHF), angina pectoris, or myocardial infarction.
(c) The patient has uncontrolled hypertension.
(d) The patient has infection, peptic ulcer, or unstable diabetes mellitus.
(e) The patient has been treated with live virus vaccines within 8 weeks before the first administration of study drug.
(f) The patient has impaired hepatic or renal function.
(g) The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
(h) The patient has used an investigational drug within 1 month before the screening visit.
(i) The patient has a known hypersensitivity to any of the study drugs or to their active ingredients.
(j) The patient has an inflammatory breast cancer.
(k) The patient has any other malignancies within 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer).



Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Patients with human epidermal growth factor receptor-2 (HER2) positive stage II or III breast cancer
MedDRA version: 9.1 Level: LLT Classification code 10065430 Term: HER-2 positive breast cancer

Intervention(s)

Trade Name: MYOCET
Pharmaceutical Form: Powder for concentrate for solution for infusion
Current Sponsor code: CEP-19562
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Trade Name: Cyclophosphamide 1 g
Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
CAS Number: 6055192
Other descriptive name: CYCLOPHOSPHAMIDE MONOHYDRATE
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Cyclophosphamide 500 mg
Product Name: Cyclophosphamide
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
CAS Number: 6055192
Other descriptive name: CYCLOPHOSPHAMIDE MONOHYDRATE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Herceptin
Product Name: Trastuzumab
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Trastuzumab
Other descriptive name: TRASTUZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Taxotere 80 mg
Product Name: Docetaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Docetaxel
CAS Number: 148408-66-6
Other descriptive name: DOCETAXEL TRIHYDRATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Taxotere 20 mg
Product Name: Docetaxel
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Docetaxel
CAS Number: 148408-66-6
Other descriptive name: DOCETAXEL TRIHYDRATE
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 40-

Trade Name: Doxorubicin Rapid Dissolution
Product Name: Free doxorubicin
Pharmaceutical Form: Powder for injection*
INN or Proposed INN: DOXORUBICIN HYDROCHLORIDE
CAS Number: 25316409
Current Sponsor code: Free doxorubicin
Concentration unit: mg milli

Primary Outcome(s)

Secondary Objective: To compare the efficacy of each treatment group as assessed by:
• the proportion of patients who achieve pathological complete response (pCR) in breast and axillary lymph node
• the proportion of patients who achieve an objective response (complete response[CR] or partial response [PR]) as defined by World Health Organization (WHO)
• the proportion of patients with conservative surgery
• the proportion of patients with progression-free survival (PFS) 2 years after being randomly assigned to treatment.
To compare the safety of each treatment assessed by the following:
• the occurrence of New York Health Association (NYHA) functional class III or IV congestive heart failure (CHF) at any time during the study
• a reduction from baseline left ventricular ejection fraction (LVEF) at any time during the study
•occurrence of adverse events throughout the study, characterized by the National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI CTCAE) version 3.

Primary end point(s): The primary efficacy measure is an outcome of pCR in breast based upon histologic examination, as confirmed by a central panel of experts, of tissue resected at the time of surgery within 4 weeks after a 24-week administration of combination therapies.

Main Objective: To compare the efficacy of up to 8 cycles (24 weeks) of MYOCET plus cyclophosphamide and trastuzumab for 4 cycles followed by docetaxel plus trastuzumab for 4 cycles (MCH?TH) with free doxorubicin plus cyclophosphamide alone for 4 cycles followed by docetaxel plus trastuzumab for 4 cycles (AC?TH), each on day 1 of a 21-day cycle, as assessed by the proportion of patients with pathological complete response (pCR) in breast.

Secondary ID(s)

C19562/2037/BC/EU

2008-000709-12-FR