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

Chemotherapy-induced Neutropenia Clinical Trial

Official title:

International 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02104830
• Other study ID #: BCD-017-3
• Status: Active, not recruiting
• Phase: Phase 3
• First received: April 2, 2014
• Last updated: April 3, 2014
• Start date: September 2013
• Est. completion date: February 2015

Study information

• Verified date: April 2014
• Source: Biocad
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: February 2015
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Chemotherapy-induced Neutropenia
• Neutropenia

Intervention

Biological:
• 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.
• 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.
• Placebo ?1

• Placebo ?2

• 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.

Locations

Country	Name	City	State
India	HCG Bangalore Institute of Oncology	Bangalore
India	M.S.Ramaiah Memorial Hospital	Bangalore
India	M.S.Ramaiah Memorial Hospital	Bangalore
Russian Federation	Arkhangelsk District Clinical Oncology Dispensary	Arkhangelsk
Russian Federation	Clinical Hospital at Chelyabinsk Railway Station	Chelyabinsk
Russian Federation	State public health institution "Regional Oncology Dispensary ?1"	Engels
Russian Federation	State public health institution "Republican Clinical Oncology Dispensary" of the Ministry of Health of the Republic of Tatarstan	Kazan
Russian Federation	Clinical Oncology Dispensary N1	Krasnodar
Russian Federation	Non-governmental healthcare institution "Central Clinical Hospital ? 2 Semashko" JSC "Russian Railways"	Moscow
Russian Federation	State Health Care Institution "Moscow City Oncology Hospital ? 62" Moscow Health Department	Moscow
Russian Federation	State public health institution "Nizhny Novgorod Regional Oncology Dispensary"	Nizhny Novgorod
Russian Federation	State budget healthcare institution Omsk region "Clinical Oncology Dispensary"	Omsk
Russian Federation	State Health Care Institution "Orenburg Regional Clinical Oncology Dispensary"	Orenburg
Russian Federation	Perm Region Oncology Dispensary	Perm
Russian Federation	Pyatigorsk Oncology Center	Pyatigorsk
Russian Federation	Federal State Educational Institution of Higher Professional Education "Mordovia State University N.P. Ogareva "	Saransk
Russian Federation	State Health Care Institution "Oncologic Dispensary ? 2" Health Department of Krasnodar Area	Sochi
Russian Federation	Military Medical Academy named after S.M. Kirov	St.Petersburg
Russian Federation	N.N.Petrov Oncology Research Center	St.Petersburg
Russian Federation	State Budget Institution health care "Tula Regional Oncology Dispensary"	Tula
Russian Federation	State public health institution "Regional Clinical Oncology Dispensary"	Ulyanovsk
Russian Federation	State Health Care Institution "Volgograd Regional Clinical Oncology Dispensary ? 1"	Volgograd
Russian Federation	Volgograd Regional Oncology Dispensary ?3	Volgograd
Russian Federation	State public health institution "Voronezh Regional Clinical Oncology Dispensary"	Voronezh
Ukraine	Donetsk City Oncology Dispensary	Donetsk
Ukraine	Donetsk Regional Antitumor Center	Donetsk
Ukraine	Kharkiv Regional Clinical Oncology Center	Kharkiv
Ukraine	Zakarpatskyi Regional Clinical Oncology Center	Uzhhorod
Ukraine	Vinnytsia Regional Clinical Oncology Dispensary	Vinnytsia

Sponsors (1)

Lead Sponsor	Collaborator
Biocad

Countries where clinical trial is conducted

India,  Russian Federation,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	The duration of grade 4 neutropenia from the 2nd to 4th cycles;		12 weeks	Yes
Secondary	The incidence of severe neutropenia (grade 3-4)		16 weeks	Yes