Study of the Efficacy and Safety of Empegfilgrastim for Neutropenia Prophylaxis in Breast Cancer Patients

Multicenter Randomized Double-blind Phase III Clinical Study Comparing the Efficacy and Safety of a Single Dose Extimia® Versus Daily Filgrastim for Neutropenia Prophylaxis in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy

The purpose of the study is to compare safety and efficacy of a single dose of empegfilgrastim and daily dosing of filgrastim for prevention of neutropenia in patients receiving AT (docetaxel 75 mg/m2 + doxorubicin 50 mg/m2).

BCD-017-3 is an double-blind randomized phase III clinical study to compare the incidence of CTCAE grade 3/4 neutropenia after a single administration of recombinant human pegylated filgrastim empegfilgrastim (Extimia®) at a dose of 6 or 7.5 mg versus daily administration of filgrastim at a dose of 5 μg/kg/day for neutropenia prophylaxis in breast cancer patients receiving myelosuppressive chemotherapy.

The study also includes the following determination of pharmacokinetic parameters after repeated administration of the study drug.

Inclusion Criteria:

• Signed informed consent form;
• Histologically verified diagnosis of stage IIb/III/IV breast cancer;
• Age of 18-70 years inclusive;
• Life expectancy of at least 6 months after inclusion in the study;
• If the patient had received the chemotherapy for breast cancer, it should be finished 30 days before the beginning of the study;
• ECOG Performance Status of 0- 2, not increasing within during 2 weeks before randomization;
• ANC level of 1500/μL and more at the beginning of the study
• Platelet count of 100 000/μL and more at the beginning of the study
• Hemoglobin level of 90 g/l and more
• Creatinine level <1.5 mg/dl
• Total bilirubin level <1.5 × the upper limit of normal (ULN)
• ALT and/or AST levels <2.5×ULN (5×ULN for patients with liver metastases);
• Alkaline phosphatase <5×ULN;
• Left ventricular ejection fraction >50% and more;
• If the patient had received adjuvant and/or neoadjuvant therapy, the cumulative dose of anthracyclines should not exceed 250 mg/m2 for doxorubicin or 540 mg/m2 for epirubicin,if in this study planned 6 cycles of chemotherapy ;
• If the patient had received adjuvant and/or neoadjuvant therapy, the cumulative dose of anthracyclines should not exceed 350 mg/m2 for doxorubicin or 660 mg/m2 for epirubicin,if in this study planned 4 cycles of chemotherapy ;
• Ability of the participant to follow the protocol requirements, according to the Investigator's opinion;
• Patients of childbearing potential must implement reliable contraceptive measures during the study treatment, starting 4 weeks prior randomization and for 6 months after the last administration of the study drug;
• Patients should be able to follow the Protocol procedures (according to Investigator's assessment.

Exclusion Criteria:

• Patient has received two or more chemotherapy regimens for the metastatic breast cancer;
• Documented hypersensitivity to filgrastim, pegfilgrastim, docetaxel, doxorubicin, dexamethasone and/or its excipients, PEGylated drugs, recombinant proteins.
• Pregnancy or breastfeeding;
• Systemic antibiotic therapy within 72 h prior empegfilgrastim/filgrastim administration;
• Concomitant radiotherapy (except selective radiotherapy of bone metastases);
• Surgery, radiotherapy (except selective radiotherapy of bone metastases), administration of any experimental drugs within 30 days prior randomization;
• History of bone marrow/stem cell transplantation;
• Conditions limiting the patient's ability to follow the protocol;
• CTCAE grade 3-4 neuropathy;
• HIV, HCV, HBV, T.Pallidum infection(s);
• Acute or active chronic infections;
• Severe concurrent diseases (for example, severe arterial hypertension, severe heart failure, and other);
• Severe depression, schizophrenia, any other mental disorders;
• Obstacles in intravenous administration of study drugs;
• Simultaneous participation in other clinical trials, previous participation in other clinical trials within 30 days before entering into the trial, previous participation in the same trial.