Dose finding study to evaluate the pharmacodynamics, pharmacokinetics, efficacy and safety of balugrastim in pediatric patients diagnosed with solid tumors receiving chemotherapy.

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2012-005432-28-SK
• Date of registration: 14/10/2013
• Prospective Registration: No
• Primary sponsor: Teva Pharmaceuticals Industries Ltd.
• Public title: Dose finding study to evaluate the pharmacodynamics, pharmacokinetics, efficacy and safety of balugrastim in pediatric patients diagnosed with solid tumors receiving chemotherapy.
• Scientific title: An open label, randomized, active controlled, dose finding study to evaluate the pharmacodynamics, pharmacokinetics, efficacy and safety of balugrastim at doses of 300 µg/kg and 670 µg/kg in pediatric patients diagnosed with solid tumors receiving chemotherapy.
• Date of first enrolment: 09/10/2013
• Target sample size: 36
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-005432-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Czech Republic, Georgia, Hungary, Romania, Russian Federation, Slovakia, Ukraine

Contacts

• Name: Clinical Project Physician
• Affiliation: Merckle GmbH a member of the Ratiopharm Group,a subsidiary of Teva Pharmaceutical Industries Ltd.

• Name: Clinical Project Physician
• Affiliation: Merckle GmbH a member of the Ratiopharm Group,a subsidiary of Teva Pharmaceutical Industries Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
a. Histologically- or cytologically-confirmed solid tumor in a patient for whom the study chemotherapy regimen (vincristine plus ifosfamide plus doxorubicin plus etoposide [VIDE], vincristine plus doxorubicin plus cyclophosphamide alternating with ifosfamide plus etoposide [VDC/IE], ifosfamide plus vincristine plus actinomycin D [IVA] or ifosfamide plus vincristine plus adriamycin [IVAd]) is considered an appropriate treatment.
b. Minimum body weight (BW) of 15 kg
c. Life expectancy of at least 3 months with appropriate therapy
d. Female or male children and adolescents aged 2 to 17 years
e. Written informed consent provided by parent(s)/legal representative(s) of the pediatric patient and patient’s assent if appropriate at the time of screening.
f. Fertile patients (male or female) must use highly reliable contraceptive measures (ie, two of the following: oral contraception, implants, injections, barrier contraception, and intrauterine device, or vasectomized/sterilized partners, or sexual abstinence). For the purposes of this study, a fertile female patient is any female patient who has experienced menarche and who has not undergone tubal ligation.
g. Female patients who have attained menarche must have a negative urine pregnancy test at the screening visit.
h. White blood cell (WBC) count >2.5 x 10(9)/L, absolute neutrophil count (ANC) =1.5 x 10(9)/L, and platelet count =100 x 10(9)/L (at screening and prior to chemotherapy)
Are the trial subjects under 18? yes
Number of subjects for this age range: 36
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
a. Primary myeloid disorders
b. Previous chemotherapy or wide-field irradiation to the pelvis
c. Previous exposure to filgrastim, pegfilgrastim, lenograstim or other granulocyte-colony stimulating factor (G-CSF) less than 6 months before randomization.
d. Known hypersensitivity to filgrastim, pegfilgrastim, lenograstim or any balugrastim excipients
e. Pregnancy or breastfeeding (if a patient becomes pregnant during the study she will be withdrawn from the study).
f. Major surgery, serious infection, serious trauma or compound medical procedure within the 4 weeks prior to the first study drug dose.
g. Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical exams, electrocardiogram (ECG), laboratory tests or imaging.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neutropenia induced by chemotherapy in patients with solid tumors
MedDRA version: 14.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Balugrastim
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BALUGRASTIM
CAS Number: 527698-09-5
Current Sponsor code: CG10639, CMO1032
Other descriptive name: Neugranin, Albugranin
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Neupogen


Pharmaceutical Form: Solution for injection
INN or Proposed INN: FILGRASTIM
CAS Number: 121181-53-1
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 300-

Primary Outcome(s)

Primary end point(s): 1.Area under the curve of ANC (AUCANC)
2.DSN
3.Incidence of severe neutropenia
4.Frequency of febrile neutropenia (defined as body temperature >38.5°C for more than one hour [axillary measurement] and ANC <0.5 x 10(9)/L) by cycle
5. Pk endpoints as per Protocol

Secondary Objective: • To document the duration of severe neutropenia (DSN) and the incidence of febrile neutropenia in Cycle 1 of chemotherapy
• To assess safety, tolerability and immunogenicity of balugrastim.

Main Objective: The primary objective of this study is to find the optimal dose of balugrastim by characterizing its pharmacokinetics (PK), and by comparing the pharmacodynamics (PD) of balugrastim to filgrastim during Cycle 1 in children receiving chemotherapy.

Timepoint(s) of evaluation of this end point: 1.Cycle 1
2-3.Cycles 1-4
4.Cycles 1-4
5.Cycle 1

Secondary Outcome(s)

Secondary end point(s): • ANC (absolute neutrophil count) nadir (measured in 10(9)/L), which is the lowest ANC recorded
• Time to ANC nadir, which is the time from the beginning of chemotherapy up to the occurrence of the ANC nadir
• Time to ANC recovery (ANC >1.5 x 10(9)/L) from nadir in all treatment cycles

Timepoint(s) of evaluation of this end point: All treatment cycles

Secondary ID(s)

2012-005432-28-HU

106588

NEUGR-005

Source(s) of Monetary Support

Merckle GmbH,a member of the Ratiopharm Group a subsidiary of Teva Pharmaceutical Industries Ltd.