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Study of the Efficacy and Safety of Empegfilgrastim for Neutropenia Prophylaxis in Breast Cancer Patients

Primary Purpose

Chemotherapy-induced Neutropenia

Status

Completed

Phase

Phase 3

Locations

Russian Federation

Study Type

Interventional

Intervention

Empegfilrastim 6 mg

Filgrastim

Placebo №1

Placebo №2

Empegfilrastim 7.5 mg

About this trial

This is an interventional supportive care trial for Chemotherapy-induced Neutropenia focused on measuring empegfilgrastim, pegylated filgrastim, neutropenia, febrile neutropenia, chemotherapy-associated neutropenia, breast cancer, docetaxel, doxorubicin

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Arkhangelsk District Clinical Oncology Dispensary
Clinical Hospital at Chelyabinsk Railway Station
State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan
Non-governmental healthcare institution "Central Clinical Hospital № 2 Semashko" JSC "Russian Railways"
State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department
State public health institution "Nizhny Novgorod Regional Oncology Dispensary"
Perm Region Oncology Dispensary
Pyatigorsk Oncology Center
Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
N.N.Petrov Oncology Research Center
State public health institution "Regional Clinical Oncology Dispensary"
Volgograd Regional Oncology Dispensary №3
State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Empegfilgrastim 6 mg

Empegfilgrastim 7.5 mg

Filgrastim

Arm Description

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.

Outcomes

Primary Outcome Measures

Duration of Neutropenia CTCAE Grade 4

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

The Duration of Grade 4 Neutropenia From the 2nd (Week 6) to 4th Cycle (Week 12);

The Incidence of Severe Neutropenia (Grade 3-4)

Low Level (Nadir) ANC x 10^9/L

Neutropenia Duration, Any Grade

Duration From ANC Nadir to ANC < 2.0 x 10^9/L

Full Information

NCT ID

NCT02104830

First Posted

April 2, 2014

Last Updated

August 31, 2016

Sponsor

Biocad

1. Study Identification

Unique Protocol Identification Number

NCT02104830

Brief Title

Study of the Efficacy and Safety of Empegfilgrastim for Neutropenia Prophylaxis in Breast Cancer Patients

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2016

Overall Recruitment Status

Completed

Study Start Date

September 2013 (undefined)

Primary Completion Date

June 2014 (Actual)

Study Completion Date

October 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Biocad

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chemotherapy-induced Neutropenia

Keywords

empegfilgrastim, pegylated filgrastim, neutropenia, febrile neutropenia, chemotherapy-associated neutropenia, breast cancer, docetaxel, doxorubicin

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

135 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Empegfilgrastim 6 mg

Arm Type

Experimental

Arm Description

Arm Title

Empegfilgrastim 7.5 mg

Arm Type

Experimental

Arm Description

Arm Title

Filgrastim

Arm Type

Active Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

Empegfilrastim 6 mg

Other Intervention Name(s)

Extimia, metpegfilgrastim, pegylated filgrastim, peg-GCSF

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Filgrastim

Other Intervention Name(s)

GCSF

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Placebo №1

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Placebo №2

Intervention Description

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.

Intervention Type

Biological

Intervention Name(s)

Empegfilrastim 7.5 mg

Other Intervention Name(s)

Extimia, metpegfilgrastim, pegylated filgrastim, peg-GCSF

Intervention Description

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.

Primary Outcome Measure Information:

Title

Duration of Neutropenia CTCAE Grade 4

Description

Time Frame

3 weeks

Secondary Outcome Measure Information:

Title

The Duration of Grade 4 Neutropenia From the 2nd (Week 6) to 4th Cycle (Week 12);

Time Frame

2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)

Title

The Incidence of Severe Neutropenia (Grade 3-4)

Time Frame

16 weeks

Title

Low Level (Nadir) ANC x 10^9/L

Time Frame

1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)

Title

Neutropenia Duration, Any Grade

Time Frame

1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)

Title

Duration From ANC Nadir to ANC < 2.0 x 10^9/L

Time Frame

1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials: