Chemotherapy-induced Neutropenia
Conditions
Keywords
empegfilgrastim, pegylated filgrastim, neutropenia, febrile neutropenia, chemotherapy-associated neutropenia, breast cancer, docetaxel, doxorubicin
Brief summary
The purpose of the study is to compare safety and efficacy of a single dose of empegfilgrastimt a dose of 3 or 6 mg versus daily administration of filgrastim at a dose of 5 μg/kg/day.
Detailed description
BCD-017-2 is an open-label randomized phase II 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 3 or 6 mg versus daily administration of filgrastim at a dose of 5 μg/kg/day for neutropenia prophylaxis in breast cancer patients receiving myelosuppressive chemotherapy.
Interventions
BIOLOGICALempegfilrastim
Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg.
BIOLOGICALfilgrastim
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.
Sponsors
Biocad
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent form; * Histologically verified diagnosis of stage IIb/III/IV breast cancer; * Age of 18-70 years inclusive; * 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, 1 or 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 500 mg/m2 for doxorubicin or 500 mg/m2 for epirubicin; * 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.
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 2/4 neuropathy * HIV, HCV, HBV, T.Pallidum infection(s); * Acute or active chronic infections.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| CTCAE Grade 3/4 Neutropenia Incidence | 21 days |
Secondary
| Measure | Time frame |
|---|---|
| Mean Duration of CTCAE Grade 4 Neutropenia | 21 days |
| The Duration of Any Grade Neutropenia | 21 days |
| Low Level (Nadir) ANC x 10^9/L | 21 days |
| Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy | 21 days |
| Incidence of Febrile Neutropenia | 21 days |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Empegfilgrastim 3 mg Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy
empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg. | 21 |
| Empegfilgrastim 6 mg Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy
empegfilrastim: Empegfilgrastim is supplied as solution for injection 3 mg/ml. Empegfilgrastim is to be administered 24 h after the chemotherapy at dose of 3 or 6 mg. | 20 |
| Filgrastim Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy
filgrastim: 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. | 19 |
| Total | 60 |
Baseline characteristics
| Characteristic | Empegfilgrastim 3 mg | Empegfilgrastim 6 mg | Filgrastim | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 20 Participants | 19 Participants | 60 Participants |
| Age, Continuous | 54.0 years | 53.5 years | 48.7 years | 53.5 years |
| Duration of a disease | 0.8 months | 0.6 months | 0.5 months | 0.65 months |
| Expression of hormone receptors deficiency estrogen and progesterone receptors | 9 participants | 9 participants | 9 participants | 27 participants |
| Expression of hormone receptors estrogen and progesterone receptors | 7 participants | 10 participants | 7 participants | 24 participants |
| Expression of hormone receptors estrogen receptors | 4 participants | 0 participants | 2 participants | 6 participants |
| Expression of hormone receptors no data | 1 participants | 1 participants | 1 participants | 3 participants |
| Gender Female | 21 Participants | 20 Participants | 19 Participants | 60 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HER2 expression 1+ | 6 participants | 3 participants | 3 participants | 12 participants |
| HER2 expression 2+ | 3 participants | 4 participants | 3 participants | 10 participants |
| HER2 expression 3+ | 6 participants | 3 participants | 8 participants | 17 participants |
| HER2 expression deficiency HER2 expression | 5 participants | 9 participants | 5 participants | 19 participants |
| HER2 expression no data | 1 participants | 1 participants | 0 participants | 2 participants |
| Histologic type of a breast cancer ductal | 15 participants | 11 participants | 15 participants | 41 participants |
| Histologic type of a breast cancer ductal/lobular | 1 participants | 0 participants | 0 participants | 1 participants |
| Histologic type of a breast cancer lobular | 0 participants | 3 participants | 0 participants | 3 participants |
| Histologic type of a breast cancer medullar | 2 participants | 0 participants | 0 participants | 2 participants |
| Histologic type of a breast cancer no data | 3 participants | 6 participants | 4 participants | 13 participants |
| History previous therapy of breast cancer no | 16 participants | 15 participants | 15 participants | 46 participants |
| History previous therapy of breast cancer yes | 5 participants | 5 participants | 4 participants | 14 participants |
| Region of Enrollment Russian Federation | 21 participants | 20 participants | 19 participants | 60 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 21 | 20 / 20 | 19 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 20 | 2 / 19 |
Outcome results
Primary
CTCAE Grade 3/4 Neutropenia Incidence
Time frame: 21 days
Population: Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 \[expected time of nadir\] were excluded from analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empegfilgrastim 3 mg | CTCAE Grade 3/4 Neutropenia Incidence | 18 participants |
| Empegfilgrastim 6 mg | CTCAE Grade 3/4 Neutropenia Incidence | 13 participants |
| Filgrastim | CTCAE Grade 3/4 Neutropenia Incidence | 11 participants |
p-value: <0.05Fisher Exact
Secondary
Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy
Time frame: 21 days
Population: Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 \[expected time of nadir\] were excluded from analysis)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Empegfilgrastim 3 mg | Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy | 4.8 days | Standard Deviation 1.64 |
| Empegfilgrastim 6 mg | Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy | 3.8 days | Standard Deviation 2.04 |
| Filgrastim | Duration of Neutropenia From Nadir to ANC < 2,0 x 10^9 Cells/L on the First Cycle of Chemotherapy | 3.00 days | Standard Deviation 1.71 |
Secondary
Incidence of Febrile Neutropenia
Time frame: 21 days
Population: Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 \[expected time of nadir\] were excluded from analysis)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Empegfilgrastim 3 mg | Incidence of Febrile Neutropenia | 1 participants |
| Empegfilgrastim 6 mg | Incidence of Febrile Neutropenia | 1 participants |
| Filgrastim | Incidence of Febrile Neutropenia | 0 participants |
Secondary
Low Level (Nadir) ANC x 10^9/L
Time frame: 21 days
Population: Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 \[expected time of nadir\] were excluded from analysis)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Empegfilgrastim 3 mg | Low Level (Nadir) ANC x 10^9/L | 0.57 cells x 10^9/L |
| Empegfilgrastim 6 mg | Low Level (Nadir) ANC x 10^9/L | 0.75 cells x 10^9/L |
| Filgrastim | Low Level (Nadir) ANC x 10^9/L | 0.82 cells x 10^9/L |
Secondary
Mean Duration of CTCAE Grade 4 Neutropenia
Time frame: 21 days
Population: Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 \[expected time of nadir\] were excluded from analysis)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Empegfilgrastim 3 mg | Mean Duration of CTCAE Grade 4 Neutropenia | 0.43 days | Standard Deviation 0.5 |
| Empegfilgrastim 6 mg | Mean Duration of CTCAE Grade 4 Neutropenia | 0.40 days | Standard Deviation 0.49 |
| Filgrastim | Mean Duration of CTCAE Grade 4 Neutropenia | 0.33 days | Standard Deviation 0.47 |
Secondary
The Duration of Any Grade Neutropenia
Time frame: 21 days
Population: Modified intention-to-treat population (analysis included patients who received at least 1 injection of study drug. Patients who had missed blood sampling on visit 5 \[expected time of nadir\] were excluded from analysis)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Empegfilgrastim 3 mg | The Duration of Any Grade Neutropenia | 1.86 days | Standard Deviation 1.39 |
| Empegfilgrastim 6 mg | The Duration of Any Grade Neutropenia | 1.0 days | Standard Deviation 0.79 |
| Filgrastim | The Duration of Any Grade Neutropenia | 0.78 days | Standard Deviation 0.43 |