Study of the Efficacy and Safety of Empegfilgrastim for Neutropenia Prophylaxis in Breast Cancer Patients
- Conditions
- Chemotherapy-induced Neutropenia
- Interventions
- Biological: FilgrastimBiological: Empegfilrastim 6 mgBiological: Placebo №2Biological: Empegfilrastim 7.5 mgBiological: Placebo №1
- Registration Number
- NCT02104830
- Lead Sponsor
- Biocad
- Brief Summary
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).
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 135
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Filgrastim Filgrastim 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. Empegfilgrastim 6 mg Placebo №2 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 Empegfilgrastim 7.5 mg Placebo №2 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 Empegfilgrastim 7.5 mg Empegfilrastim 7.5 mg 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 Filgrastim Placebo №1 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. Empegfilgrastim 6 mg Empegfilrastim 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
- Primary Outcome Measures
Name Time Method Duration of Neutropenia CTCAE Grade 4 3 weeks 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).
- Secondary Outcome Measures
Name Time Method The Duration of Grade 4 Neutropenia From the 2nd (Week 6) to 4th Cycle (Week 12); 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12) Neutropenia Duration, Any Grade 1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12) The Incidence of Severe Neutropenia (Grade 3-4) 16 weeks Low Level (Nadir) ANC x 10^9/L 1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12) Duration From ANC Nadir to ANC < 2.0 x 10^9/L 1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)
Trial Locations
- Locations (13)
Pyatigorsk Oncology Center
🇷🇺Pyatigorsk, Russian Federation
Perm Region Oncology Dispensary
🇷🇺Perm, Russian Federation
Clinical Hospital at Chelyabinsk Railway Station
🇷🇺Chelyabinsk, Russian Federation
State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan
🇷🇺Kazan, Russian Federation
Non-governmental healthcare institution "Central Clinical Hospital № 2 Semashko" JSC "Russian Railways"
🇷🇺Moscow, Russian Federation
State public health institution "Nizhny Novgorod Regional Oncology Dispensary"
🇷🇺Nizhny Novgorod, Russian Federation
State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department
🇷🇺Moscow, Russian Federation
State public health institution "Regional Clinical Oncology Dispensary"
🇷🇺Ulyanovsk, Russian Federation
Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
🇷🇺Saransk, Russian Federation
N.N.Petrov Oncology Research Center
🇷🇺St.Petersburg, Russian Federation
Volgograd Regional Oncology Dispensary №3
🇷🇺Volgograd, Russian Federation
State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
🇷🇺Volgograd, Russian Federation
Arkhangelsk District Clinical Oncology Dispensary
🇷🇺Arkhangelsk, Russian Federation