E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Neutropenia induced by chemotherapy in patients with solid tumors |
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E.1.1.1 | Medical condition in easily understood language |
Neutropenia induced by chemotherapy in patients with solid tumors |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065252 |
E.1.2 | Term | Solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
• 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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 10 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) |
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E.4 | Principal exclusion criteria |
a. Primary myeloid disorders
b. Prior radiation therapy within 4 weeks of randomization into this study.
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 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.
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. |
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.Cycle 1
2-3.Cycles 1-4
4.Cycles 1-4
5.Cycle 1 |
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E.5.2 | 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 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Czech Republic |
Georgia |
Hungary |
Romania |
Russian Federation |
Slovakia |
Ukraine |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |