Clinical trial NCT02104830: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chemotherapy-induced Neutropenia
Keywords: empegfilgrastim
pegylated filgrastim
neutropenia
febrile neutropenia
chemotherapy-associated neutropenia
breast cancer
docetaxel
doxorubicin
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2014-04-04
Enrollment: 135
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

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.

Primary outcomes:
measure: Duration of Neutropenia CTCAE Grade 4
timeFrame: 3 weeks
Secondary outcomes:
measure: The Duration of Grade 4 Neutropenia From the 2nd (Week 6) to 4th Cycle (Week 12);
timeFrame: 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)
measure: The Incidence of Severe Neutropenia (Grade 3-4)
timeFrame: 16 weeks
measure: Low Level (Nadir) ANC x 10^9/L
timeFrame: 1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)
measure: Neutropenia Duration, Any Grade
timeFrame: 1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)
measure: Duration From ANC Nadir to ANC < 2.0 x 10^9/L
timeFrame: 1st cycle (week 3), 2nd cycle (week 6), 3rd cycle (week 9), 4th cycle (week 12)
Other outcomes:
Locations:
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk District Clinical Oncology Dispensary
city: Chelyabinsk
country: Russian Federation
facility: Clinical Hospital at Chelyabinsk Railway Station
city: Kazan
country: Russian Federation
facility: State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan
city: Moscow
country: Russian Federation
facility: Non-governmental healthcare institution "Central Clinical Hospital № 2 Semashko" JSC "Russian Railways"
city: Moscow
country: Russian Federation
facility: State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department
city: Nizhny Novgorod
country: Russian Federation
facility: State public health institution "Nizhny Novgorod Regional Oncology Dispensary"
city: Perm
country: Russian Federation
facility: Perm Region Oncology Dispensary
city: Pyatigorsk
country: Russian Federation
facility: Pyatigorsk Oncology Center
city: Saransk
country: Russian Federation
facility: Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
city: St.Petersburg
country: Russian Federation
facility: N.N.Petrov Oncology Research Center
city: Ulyanovsk
country: Russian Federation
facility: State public health institution "Regional Clinical Oncology Dispensary"
city: Volgograd
country: Russian Federation
facility: Volgograd Regional Oncology Dispensary №3
city: Volgograd
country: Russian Federation
facility: State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
Study officials:
affiliation: Biocad
name: Roman Ivanov, MD, PhD
role: STUDY_DIRECTOR
affiliation: Federal State Institution "Moscow Research Oncological Institute P.A.Gertsena "of the Ministry of Health of the Russian Federation
name: Larisa Bolotina, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State public health institution "Regional Oncology Dispensary №1
name: Olga Brichkova, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health Arkhangelsk region "Arkhangelsk Clinical Oncology Dispensary"
name: Olga Burdaeva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Non-governmental healthcare institution "Central Clinical Hospital № 2 Semashko" JSC "Russian Railways"
name: Byakhov Michael, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health Stavropol area "Piatigorsky Oncology Dispensary"
name: Vladimir Vladimirov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State budget healthcare institution Omsk region "Clinical Oncology Dispensary"
name: Rinat Galiulin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health "Chelyabinsk Regional Clinical Oncology Dispensary"
name: Oleg Gladkov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health "Clinical Oncology Dispensary № 1" of the Ministry of Health of the Krasnodar area
name: Irina Davydenko, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State public health institution "Voronezh Regional Clinical Oncology Dispensary"
name: Victoria Elkova, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State public health institution "Kursk Regional Oncology Dispensary"
name: Igor Lifirenko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health "Volgograd regional oncologic dispensary № 3"
name: Nadezhda Kovalenko, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health "Samara Regional Clinical Oncology Dispensary"
name: Michael Kopp, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: S. M. Kirov Military Medical Academy of the Ministry of Defense of the Russian Federation
name: Bogdan Kotiv, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution of Health Stavropol area "Stavropol Regional Clinical Oncology Dispensary"
name: Natalia Levchenko, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State public health institution "Nizhny Novgorod Regional Oncology Dispensary"
name: Marina Matrosova, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan
name: Guzel Mukhametshina, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State public health institution "Regional Clinical Oncology Dispensary"
name: Sergei Panchenko, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Regional State Health Care Institution "Orlovsky Oncology Dispensary"
name: Alexander Pecheny, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Budget Institution health care "Tula Regional Oncology Dispensary"
name: Igor Pimenov, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Health Care Institution of Tyumen Region "Regional Oncological Dispensary"
name: Andrei Sinykov, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "
name: Pavel Skopin, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Health Care Institution "Moscow City Oncology Hospital № 62" Moscow Health Department
name: Daniil Stroyakovsky
role: PRINCIPAL_INVESTIGATOR
affiliation: "Russian Oncological Scientific Center N.N.Blokhin" Russian Academy of Sciences
name: Sergei Tyulyandin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Health Care Institution "Oncologic Dispensary № 2" Health Department of Krasnodar Area
name: Dmitriy Udovica, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Health Care Institution "Perm Regional Oncology Dispensary"
name: Andrei Horinko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: N.N. Petrov Oncology Research Center of the Ministry of Health of the Russian Federation
name: Petr Krivorotko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Non-governmental healthcare institution "Chelyabinsk Road Clinical Hospital" JSC "Russian Railways"
name: Yulia Shapovalova, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary № 1"
name: Ludmila Sheveleva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Health Care Institution "Orenburg Regional Clinical Oncology Dispensary"
name: Vadim Shirinkin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bangalore Institute of Oncology
name: Shekar Patil, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mazumdar Shaw Cancer Center and Narayana Hrudayalaya Multispecialty Hosptial
name: Prasad Narayanan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.S.Ramaiah Memorial Hospital
name: Nalini Kilara, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Donetsk City Municipal Oncology Dispensary
name: Sergei Kulik, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Donetsk Regional oncology centers
name: Igor Sedakov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zakarpatskii Regional Clinical Oncology Dispensary
name: Andrei Rusin, MD,PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Kharkiv Regional Clinical Oncology Center
name: Yuri Vinnik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Vinnitskii Regional Oncology Dispensary
name: Sergei Odarchenko, PhD
role: PRINCIPAL_INVESTIGATOR
References: