Title
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
Phase
Phase 3Lead Sponsor
BiocadStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
Chemotherapy-induced NeutropeniaIntervention/Treatment
empegfilrastim sargramostim ...Study Participants
135The 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.
Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 6 mg.
Filgrastim should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Filgrastim should be administered daily for up to 2 weeks until the ANC has reached 10 000/mm3 following the expected chemotherapy-induced neutrophil nadir.
Placebo №1 is supplied as solution for injection 1.0 ml. Placebo №1 is to be administered 24 h after the chemotherapy at dose of 1.0.
Placebo №2 should be administered no earlier than 24 hours after the administration of cytotoxic chemotherapy. Placebo №2 is supplied as solution for injection 0.0083 ml/kg.
Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 6 mg.
Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy and placebo #2 in a dose of 0.0083 ml/kg in 24-27 hour after chemotherapy, then patient received placebo #2 in dose 0.0083 ml/kg until ANC ≥ 10x109/L or during 14 days
Patients will receive a single administration of empegfilgrastim at a dose of 7.5 mg subcutaneously, 24 h after the chemotherapy and placebo #2 in a dose of 0.0083 ml/kg in 24-27 hour after chemotherapy, then patient received placebo #2 in dose 0.0083 ml/kg until ANC ≥ 10x109/L or during 14 days
Patients will receive filgrastim at a dose of 5 μg/kg subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy and placebo #1 in dose 1.0 ml subcutaneously, 24 h after the chemotherapy.
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.
| Event Type | Organ System | Event Term | Empegfilgrastim 6 mg | Empegfilgrastim 7.5 mg | Filgrastim |
|---|
The primary endpoint, which will allow to compare the efficacy of the single dose of Extimia® versus nonpegylated daily filgrastim is the number of breast cancer patients developing CTCAE grade 3/4 neutropenia after the first AT chemotherapy cycle (doxorubicin+docetaxel).
