Pharmacodynamics, Pharmacokinetics, Efficacy and Safety of Balugrastim in Pediatric Patients With Solid Tumors

Study Overview
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Brief Summary
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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 in children receiving chemotherapy.

Official Title
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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

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: Balugrastim
* Drug: Filgrastim


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological 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. Minimum body weight of 15 kg Life expectancy of at least 3 months with appropriate therapy Female or male children and adolescents aged 2 to 17 years 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. Fertile patients (male or female) must use highly reliable contraceptive measures. Female patients who have attained menarche must have a negative urine pregnancy test at the screening visit. White blood cell (WBC) count >2.5*10^9/L, ANC ≥1.5*10^9/L, and platelet count ≥100*10^9/L (at screening and prior to chemotherapy) Exclusion Criteria: Primary myeloid disorders Prior radiation therapy within 4 weeks of randomization into this study. Previous exposure to filgrastim, pegfilgrastim, lenograstim or other G-CSF less than 6 months before randomization. Known hypersensitivity to filgrastim, pegfilgrastim, lenograstim or any balugrastim excipients Pregnancy or breastfeeding (if a patient becomes pregnant during the study she will be withdrawn from the study). Major surgery, serious infection, within 3 weeks before first administration of study drug, serious trauma or compound medical procedure within the 4 weeks prior to the first study drug dose. 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, ECG, laboratory tests or imaging.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Balugrastim 300 ug/kg<br>Balugrastim 300 μg/kg subcutaneously (SC) administration once per chemotherapy cycle, approximately 24 h after chemotherapy, up to 4 cycles | Drug: Balugrastim<br>* Balugrastim 300 ug/kg and Balugrastim 670 ug/kg<br>|
| Experimental: Balugrastim 670 μg/kg<br>Balugrastim 670 μg/kg (maximum 40 mg) SC administration once per chemotherapy cycle, approximately 24 h after chemotherapy, up to 4 cycles | Drug: Balugrastim<br>* Balugrastim 300 ug/kg and Balugrastim 670 ug/kg<br>|
| Active Comparator: Filgrastim 5 μg/kg<br>Filgrastim will be administered at a dose of 5 μg/kg SC once a day for at least 5 consecutive days or until absolute neutrophil count (ANC) has returned to ≥2*10^9/L for each chemotherapy cycle up to 4 cycles. The maximum period of filgrastim administration is 14 days in each cycle. | Drug: Filgrastim<br>* Filgrastim 5 μg/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC) of absolute neutrophil count (ANC) |  | Day 1 to 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ANC nadir | ANC nadir (measured in 10^9/L), which is the lowest ANC recorded | Baseline to Week 16 | 
| Time to ANC nadir | Time to ANC nadir, which is the time from the beginning of chemotherapy up to the occurrence of the ANC nadir | Baseline to Week 16 | 
| Time to ANC recovery | Time to ANC recovery (ANC >1.5*10^9/L) from nadir within each treatment cycle | Baseline to Week 16 | 
| Duration of severe neutropenia (DSN) | Number of days subject experiences severe neutropenia (ANC <0.5*10^9/L) | Baseline to Week 16 | 
| Incidence of severe neutropenia | Proportion of subjects who experience severe neutropenia (ANC <0.5*10^9/L) | Baseline to Week 16 | 
| Frequency of febrile neutropenia | Frequency of febrile neutropenia (defined as body temperature >38.5°C for more than one hour [axillary measurement] and ANC <0.5*10^9/L) by cycle and across all cycles. | Baseline to Week 16 | 
| Summary of Participants with Adverse Events |  | From signing of informed consent to 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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solid tumors, balugrastim