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

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

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Neutropenia
• Intervention / Treatment: Biological: empegfilrastim; Biological: filgrastim

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Arkhangelsk District Clinical Oncology Dispensary
  • Perm, Russian Federation, 614066
    • Perm Region Oncology Dispensary
  • St.Petersburg, Russian Federation, 197758
    • N.N.Petrov Oncology Research Center
  • St.Petersburg, Russian Federation
    • Russian scientific center of radiology and surgery technologies
  • Volgograd, Russian Federation, 400138
    • Volgograd District Oncology Dispensary №1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Empegfilgrastim 3 mg; Patients will receive a single administration of empegfilgrastim at a dose of 3 mg subcutaneously , 24 h after the chemotherapy	Biological: 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.; Other Names: pegylated filgrastim; Extimia; BCD-017; metpegfilgrastim; peg-GCSF; empegfilgrastim
EXPERIMENTAL: Empegfilgrastim 6 mg; Patients will receive a single administration of empegfilgrastim at a dose of 6 mg subcutaneously, 24 h after the chemotherapy	Biological: 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.; Other Names: pegylated filgrastim; Extimia; BCD-017; metpegfilgrastim; peg-GCSF; empegfilgrastim
ACTIVE_COMPARATOR: 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	Biological: 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.; Other Names: GCSF

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome 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

Collaborators and Investigators

• Sponsor: Biocad
• Investigators: Study Director: Roman A. Ivanov, MD, PhD, Biocad

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (ACTUAL): January 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: March 30, 2012
• First Submitted That Met QC Criteria: March 30, 2012
• First Posted (ESTIMATE): April 2, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 5, 2016
• Last Update Submitted That Met QC Criteria: October 24, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: breast cancer; neutropenia; febrile neutropenia; docetaxel; doxorubicin; empegfilgrastim; pegylated filgrastim; chemotherapy-associated neutropenia
• Additional Relevant MeSH Terms: Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Neutropenia; Physiological Effects of Drugs; Immunologic Factors; Adjuvants, Immunologic; Lenograstim
• Other Study ID Numbers: BCD-017-2