Dose-finding Study of Empegfilgrastim for Neutropenia Prophylaxis in Patients With Breast Cancer

Study Overview
=================
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.

Official Title
-----------------
Randomized Multicenter Open-label Phase II Clinical Study Comparing the Efficacy and Safety of the Single Dose of Extimia® Versus Daily Filgrastim for Neutropenia Prophylaxis in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy

Conditions
-----------------
Chemotherapy-induced Neutropenia

Intervention / Treatment
-----------------
* Biological: empegfilrastim
* Biological: filgrastim


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empegfilgrastim 3 mg<br>Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy | Biological: empegfilrastim<br>* 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.<br>* Other names: empegfilgrastim;|
| Experimental: Empegfilgrastim 6 mg<br>Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy | Biological: empegfilrastim<br>* 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.<br>* Other names: empegfilgrastim;|
| Active Comparator: Filgrastim<br>Patients will receive filgrastim subcutaneously daily (until ANC 10 000/μL or for 14 days, whichever occurred first), starting 24 h after the chemotherapy | Biological: filgrastim<br>* 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.<br>* Other names: GCSF;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CTCAE Grade 3/4 Neutropenia Incidence |  | 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
empegfilgrastim, pegylated filgrastim, neutropenia, febrile neutropenia, chemotherapy-associated neutropenia, breast cancer, docetaxel, doxorubicin