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

NCT ID: NCT02104830

Last Updated: 2016-10-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30
• Study Completion Date: 2014-10-31

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.

Conditions

Chemotherapy-induced Neutropenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

Empegfilgrastim 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

Group Type: EXPERIMENTAL

Empegfilrastim 6 mg

Intervention Type: BIOLOGICAL

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.

Placebo №2

Intervention Type: BIOLOGICAL

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.

Empegfilgrastim 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

Group Type: EXPERIMENTAL

Placebo №2

Intervention Type: BIOLOGICAL

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.

Empegfilrastim 7.5 mg

Intervention Type: BIOLOGICAL

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.

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.

Group Type: ACTIVE_COMPARATOR

Filgrastim

Intervention Type: BIOLOGICAL

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.

Placebo №1

Intervention Type: BIOLOGICAL

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.

Interventions

Empegfilrastim 6 mg

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

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.

Intervention Type: BIOLOGICAL

Placebo №1

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

Placebo №2

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

Empegfilrastim 7.5 mg

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

Other Intervention Names

Extimia; metpegfilgrastim; pegylated filgrastim; peg-GCSF; GCSF; Extimia; metpegfilgrastim; pegylated filgrastim; peg-GCSF

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Biocad

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roman Ivanov, MD, PhD

Role: STUDY_DIRECTOR

Biocad

Larisa Bolotina, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Federal State Institution "Moscow Research Oncological Institute P.A.Gertsena "of the Ministry of Health of the Russian Federation

Olga Brichkova, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

State public health institution "Regional Oncology Dispensary №1

Olga Burdaeva, MD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health Arkhangelsk region "Arkhangelsk Clinical Oncology Dispensary"

Byakhov Michael, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Non-governmental healthcare institution "Central Clinical Hospital № 2 Semashko" JSC "Russian Railways"

Vladimir Vladimirov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health Stavropol area "Piatigorsky Oncology Dispensary"

Rinat Galiulin, MD

Role: PRINCIPAL_INVESTIGATOR

State budget healthcare institution Omsk region "Clinical Oncology Dispensary"

Oleg Gladkov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health "Chelyabinsk Regional Clinical Oncology Dispensary"

Irina Davydenko, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health "Clinical Oncology Dispensary № 1" of the Ministry of Health of the Krasnodar area

Victoria Elkova, MD

Role: PRINCIPAL_INVESTIGATOR

State public health institution "Voronezh Regional Clinical Oncology Dispensary"

Igor Lifirenko, MD

Role: PRINCIPAL_INVESTIGATOR

State public health institution "Kursk Regional Oncology Dispensary"

Nadezhda Kovalenko, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health "Volgograd regional oncologic dispensary № 3"

Michael Kopp, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health "Samara Regional Clinical Oncology Dispensary"

Bogdan Kotiv, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

S. M. Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation

Natalia Levchenko, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution of Health Stavropol area "Stavropol Regional Clinical Oncology Dispensary"

Marina Matrosova, MD

Role: PRINCIPAL_INVESTIGATOR

State public health institution "Nizhny Novgorod Regional Oncology Dispensary"

Guzel Mukhametshina, MD

Role: PRINCIPAL_INVESTIGATOR

State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan

Sergei Panchenko, PhD

Role: PRINCIPAL_INVESTIGATOR

State public health institution "Regional Clinical Oncology Dispensary"

Alexander Pecheny, PhD

Role: PRINCIPAL_INVESTIGATOR

Regional State Health Care Institution "Orlovsky Oncology Dispensary"

Igor Pimenov, PhD

Role: PRINCIPAL_INVESTIGATOR

State Budget Institution health care "Tula Regional Oncology Dispensary"

Andrei Sinykov, PhD

Role: PRINCIPAL_INVESTIGATOR

State Health Care Institution of Tyumen Region "Regional Oncological Dispensary"

Pavel Skopin, PhD

Role: PRINCIPAL_INVESTIGATOR

Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "

Daniil Stroyakovsky

Role: PRINCIPAL_INVESTIGATOR

State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department

Sergei Tyulyandin, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

"Russian Oncological Scientific Center N.N.Blokhin" Russian Academy of Sciences

Dmitriy Udovica, MD

Role: PRINCIPAL_INVESTIGATOR

State Health Care Institution "Oncologic Dispensary № 2" Health Department of Krasnodar Area

Andrei Horinko, MD

Role: PRINCIPAL_INVESTIGATOR

State Health Care Institution "Perm Regional Oncology Dispensary"

Petr Krivorotko, MD

Role: PRINCIPAL_INVESTIGATOR

N.N. Petrov Oncology Research Center of the Ministry of Health of the Russian Federation

Yulia Shapovalova, PhD

Role: PRINCIPAL_INVESTIGATOR

Non-governmental healthcare institution "Chelyabinsk Road Clinical Hospital" JSC "Russian Railways"

Ludmila Sheveleva, MD

Role: PRINCIPAL_INVESTIGATOR

State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"

Vadim Shirinkin, MD

Role: PRINCIPAL_INVESTIGATOR

State Health Care Institution "Orenburg Regional Clinical Oncology Dispensary"

Shekar Patil, MD

Role: PRINCIPAL_INVESTIGATOR

Bangalore Institute of Oncology

Prasad Narayanan, MD

Role: PRINCIPAL_INVESTIGATOR

Mazumdar Shaw Cancer Center and Narayana Hrudayalaya Multispecialty Hosptial

Nalini Kilara, MD

Role: PRINCIPAL_INVESTIGATOR

M.S.Ramaiah Memorial Hospital

Sergei Kulik, MD

Role: PRINCIPAL_INVESTIGATOR

Donetsk City Municipal Oncology Dispensary

Igor Sedakov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Donetsk Regional oncology centers

Andrei Rusin, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Zakarpatskii Regional Clinical Oncology Dispensary

Yuri Vinnik, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Kharkiv Regional Clinical Oncology Center

Sergei Odarchenko, PhD

Role: PRINCIPAL_INVESTIGATOR

Vinnitskii Regional Oncology Dispensary

Locations

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, , Russia

Clinical Hospital at Chelyabinsk Railway Station

Chelyabinsk, , Russia

State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan

Kazan', , Russia

Non-governmental healthcare institution "Central Clinical Hospital № 2 Semashko" JSC "Russian Railways"

Moscow, , Russia

State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department

Moscow, , Russia

State public health institution "Nizhny Novgorod Regional Oncology Dispensary"

Nizhny Novgorod, , Russia

Perm Region Oncology Dispensary

Perm, , Russia

Pyatigorsk Oncology Center

Pyatigorsk, , Russia

N.N.Petrov Oncology Research Center

Saint Petersburg, , Russia

Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "

Saransk, , Russia

State public health institution "Regional Clinical Oncology Dispensary"

Ulyanovsk, , Russia

Volgograd Regional Oncology Dispensary №3

Volgograd, , Russia

State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"

Volgograd, , Russia

Countries

Russia

Other Identifiers

BCD-017-3

Identifier Type: -

Identifier Source: org_study_id