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 10 9/L (10 to the power of 9/L) * Platelets ≥100 x 10 9/L (10 to the power of 9/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) or any prior radiotherapy to the mediastinal/pericardial region; 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-delivered products or docetaxel 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 1 of Cycle 1).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is DSN (in days) (ANC <0.5 x 10 9/L (10 to the power of 9/L) and body temperature of >38.5°C. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.2.3.1 | Comparator description |
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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 | 2 |
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 |