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

NCT02104830 | Completed Phase 3 Results

• 1 other identifier: BCD-017-3
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 13

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).

Conditions

Chemotherapy-induced Neutropenia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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).

  3 weeks

Secondary Outcomes (5)

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

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

• The Incidence of Severe Neutropenia (Grade 3-4)

  16 weeks

• Low Level (Nadir) ANC x 10^9/L

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

• Neutropenia Duration, Any Grade

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

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

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

Study Arms (3)

Empegfilgrastim 6 mg

EXPERIMENTAL

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

Biological: Empegfilrastim 6 mg; Biological: Placebo №2

Empegfilgrastim 7.5 mg

EXPERIMENTAL

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

Biological: Placebo №2; Biological: Empegfilrastim 7.5 mg

Filgrastim

ACTIVE COMPARATOR

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.

Biological: Filgrastim; Biological: Placebo №1

Interventions

Empegfilrastim 6 mg 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.

Also known as: Extimia, metpegfilgrastim, pegylated filgrastim, peg-GCSF

Empegfilgrastim 6 mg

Filgrastim 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.

Also known as: GCSF

Filgrastim

Placebo №1 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.

Filgrastim

Placebo №2 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 6 mg; Empegfilgrastim 7.5 mg

Empegfilrastim 7.5 mg 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.

Also known as: Extimia, metpegfilgrastim, pegylated filgrastim, peg-GCSF

Empegfilgrastim 7.5 mg

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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- 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 ;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Biocad: lead

Study Sites (13)

Arkhangelsk District Clinical Oncology Dispensary

Arkhangelsk, 163045, Russia

Location

Clinical Hospital at Chelyabinsk Railway Station

Chelyabinsk, Russia

Location

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

Kazan', Russia

Location

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

Moscow, Russia

Location

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

Moscow, Russia

Location

State public health institution "Nizhny Novgorod Regional Oncology Dispensary"

Nizhny Novgorod, Russia

Location

Perm Region Oncology Dispensary

Perm, 614066, Russia

Location

Pyatigorsk Oncology Center

Pyatigorsk, 357502, Russia

Location

N.N.Petrov Oncology Research Center

Saint Petersburg, 197758, Russia

Location

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

Saransk, Russia

Location

State public health institution "Regional Clinical Oncology Dispensary"

Ulyanovsk, Russia

Location

Volgograd Regional Oncology Dispensary №3

Volgograd, 404130, Russia

Location

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

Volgograd, Russia

Location

MeSH Terms

Conditions

Neutropenia; Febrile Neutropenia; Breast Neoplasms

Interventions

Filgrastim

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Roman Ivanov, Director of Clinical Trials
• Organization: Biocad

ivanov@biocad.ru

+7 (812) 380 49 33

Study Officials

• Roman Ivanov, MD, PhD

  Biocad

  STUDY DIRECTOR

• Larisa Bolotina, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Olga Brichkova, MD, PhD

  State public health institution "Regional Oncology Dispensary №1

  PRINCIPAL INVESTIGATOR

• Olga Burdaeva, MD

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

  PRINCIPAL INVESTIGATOR

• Byakhov Michael, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Vladimir Vladimirov, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Rinat Galiulin, MD

  State budget healthcare institution Omsk region "Clinical Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Oleg Gladkov, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Irina Davydenko, PhD

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

  PRINCIPAL INVESTIGATOR

• Victoria Elkova, MD

  State public health institution "Voronezh Regional Clinical Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Igor Lifirenko, MD

  State public health institution "Kursk Regional Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Nadezhda Kovalenko, PhD

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

  PRINCIPAL INVESTIGATOR

• Michael Kopp, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Bogdan Kotiv, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Natalia Levchenko, PhD

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

  PRINCIPAL INVESTIGATOR

• Marina Matrosova, MD

  State public health institution "Nizhny Novgorod Regional Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Guzel Mukhametshina, MD

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

  PRINCIPAL INVESTIGATOR

• Sergei Panchenko, PhD

  State public health institution "Regional Clinical Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Alexander Pecheny, PhD

  Regional State Health Care Institution "Orlovsky Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Igor Pimenov, PhD

  State Budget Institution health care "Tula Regional Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Andrei Sinykov, PhD

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

  PRINCIPAL INVESTIGATOR

• Pavel Skopin, PhD

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

  PRINCIPAL INVESTIGATOR

• Daniil Stroyakovsky

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

  PRINCIPAL INVESTIGATOR

• Sergei Tyulyandin, MD, PhD

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

  PRINCIPAL INVESTIGATOR

• Dmitriy Udovica, MD

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

  PRINCIPAL INVESTIGATOR

• Andrei Horinko, MD

  State Health Care Institution "Perm Regional Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Petr Krivorotko, MD

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

  PRINCIPAL INVESTIGATOR

• Yulia Shapovalova, PhD

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

  PRINCIPAL INVESTIGATOR

• Ludmila Sheveleva, MD

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

  PRINCIPAL INVESTIGATOR

• Vadim Shirinkin, MD

  State Health Care Institution "Orenburg Regional Clinical Oncology Dispensary"

  PRINCIPAL INVESTIGATOR

• Shekar Patil, MD

  Bangalore Institute of Oncology

  PRINCIPAL INVESTIGATOR

• Prasad Narayanan, MD

  Mazumdar Shaw Cancer Center and Narayana Hrudayalaya Multispecialty Hosptial

  PRINCIPAL INVESTIGATOR

• Nalini Kilara, MD

  M.S.Ramaiah Memorial Hospital

  PRINCIPAL INVESTIGATOR

• Sergei Kulik, MD

  Donetsk City Municipal Oncology Dispensary

  PRINCIPAL INVESTIGATOR

• Igor Sedakov, MD, PhD

  Donetsk Regional oncology centers

  PRINCIPAL INVESTIGATOR

• Andrei Rusin, MD,PhD

  Zakarpatskii Regional Clinical Oncology Dispensary

  PRINCIPAL INVESTIGATOR

• Yuri Vinnik, MD, PhD

  Kharkiv Regional Clinical Oncology Center

  PRINCIPAL INVESTIGATOR

• Sergei Odarchenko, PhD

  Vinnitskii Regional Oncology Dispensary

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2014
• First Posted: April 4, 2014
• Study Start: September 1, 2013
• Primary Completion: June 1, 2014
• Study Completion: October 1, 2014
• Last Updated: October 24, 2016
• Results First Posted: October 24, 2016

Record last verified: 2016-08

Locations

RU (13)