E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
This study is designed to demonstrate the therapeutic equivalence of PLIVA/Mayne filgrastim and Neupogen for the reduction in duration of neutropenia and the incidence of febrile neutropenia, in subjects receiving chemotherapy. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029354 |
E.1.2 | Term | Neutropenia |
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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 |
To demonstrate the therapeutic equivalence of Pliva/Mayne filgrastim to Neupogen. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy, safety and tolerability of PLIVA/Mayne filgrastim and Neupogen. To compare the immunogenicity of PLIVA/Mayne filgrastim and Neupogen. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Females ≥ 18 and ≤ 70 years of age; 2. Written informed consent given; 3. Subjects with invasive breast cancer appropriate for treatment with doxorubicin and docetaxel combination therapy in the neo-adjuvant, adjuvant or first line metastatic treatment setting, who have not previously received treatment with anthracyclines or taxanes; 4. Any acute adverse effects of prior therapy must have resolved to ≤ NCI CTCAE (Version 3.0) grade 1 (excluding alopecia) prior to Day 1 of Cycle 1; 5. ECOG Performance Status 0 or 1 as determined on Day 1 of Cycle 1 prior to administration of chemotherapy; 6. Adequate bone marrow function, as determined within 1 day prior to administration of chemotherapy on Day 1 of Cycle 1 and as indicated by: • Hb ≥ 10 g/dL (transfusion permitted) • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L • Platelets ≥ 100 x 109/L 7. Adequate renal and hepatic function, as determined within 1 day prior to administration of chemotherapy on Day 1 of Cycle 1 and as indicated by: • Creatinine <1.5 x ULN • Total bilirubin within normal reference range (unless elevation is known to be due to Gilbert’s disease) • Subjects must also meet one of the following criteria: a. Alkaline phosphatase within normal reference range and both AST and ALT <2.5 x ULN; or b. Alkaline phosphatase <2.5 x ULN and both AST and ALT <1.5 x ULN; or c. Alkaline phosphatase <5 x ULN and both AST and ALT within normal reference range 8. Female subjects with reproductive potential must have a negative urine pregnancy test within 3 days prior to the first dose of chemotherapy (Day 1 of Cycle 1) and must agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months after discontinuation of treatment. Acceptable methods of contraception include IUD, oral contraceptive, subdermal implant and double barrier (condom with a contraceptive sponge or contraceptive suppository); 9. Estimated life-expectancy >6 months.
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E.4 | Principal exclusion criteria |
1. Chemotherapy within the 4 weeks prior to the first dose of chemotherapy (Day 1 of Cycle 1) (or a longer period depending on the defined characteristics of the agents used e.g., 6 weeks for mitomycin); 2. Radiotherapy within the 6 weeks prior to the first dose of chemotherapy, except for localised spot radiotherapy for bone metastases (Day 1 of Cycle 1); 3. Any prior radiotherapy to the mediastinal/pericardial region; 4. Any concurrent anti-cancer therapy, including endocrine therapy (with the exception of corticosteroids), immunotherapy and monoclonal antibody therapy. Concurrent treatment with bisphosphonates is also excluded unless the subject has been on a stable dose for four weeks prior to the first dose of chemotherapy (Day 1 of Cycle 1); 5. Receipt of a non-registered, investigational agent as part of a clinical trial within 3 months prior to the first dose of chemotherapy (Day 1 of Cycle 1); 6. Receipt of a registered agent as part of a clinical trial if final study follow-up visit is within 30 days of start of chemotherapy (Day 1 of Cycle 1); 7. Prior bone marrow or stem cell transplant; 8. Any known myeloid abnormality (to include a pre-malignant myeloid condition or malignant condition); 9. Subjects who, in the Investigator’s opinion, have had extensive prior radiotherapy to a significant area of the bone marrow potentially affecting myelopoiesis; 10. Co-existing active infection, or received systemic anti-infectives for the treatment of infection within 72 hours prior to the first dose of chemotherapy (Day 1 of Cycle 1); 11. Significant cardiovascular disease as defined by: a. History of congestive heart failure requiring therapy; b. History of unstable angina pectoris or myocardial infarction within 6 months prior to screening; c. Presence of severe valvular heart disease; d. Presence of an arrhythmia requiring treatment. 12. Any co-existing medical condition that in the Investigator’s judgement will substantially increase the risk associated with the subject’s participation in the study. 13. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures; 14. Clinically symptomatic brain metastases (baseline computerized tomography (CT) or magnetic resonance imaging (MRI) scan of the brain required only if there is clinical suspicion of central nervous system metastases); 15. Known hypersensitivity to E. coli-derived products or other drugs formulated with polysorbate 80; 16. Previously received any G-CSF; 17. Uncontrolled hypercalcaemia (>NCI CTCAE (Version 3.0) grade 1); 18. Second malignancy (except adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix); 19. Pregnant or breast-feeding women; 20. Concomitant treatment with lithium or lithium products; 21. Hereditary fructose intolerance; 22. Concurrent treatment with erythropoietin or prior treatment within 4 weeks prior to the first dose of chemotherapy (Day 1of Cycle 1).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints is DSN (in days) (ANC <0.5 x 109/L) and body temperature of ≥ 38.5 ºC |
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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 | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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.8.3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
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 | Information not present in EudraCT |
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 |
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E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |