A Phase III randomised, multicentre, double-blind, therapeutic equivalence study of biosimilar G-CSF (PLIVA/Mayne filgrastim) versus Neupogen (filgrastim-Amgen) in subjects receiving doxorubicin and docetaxel as a combination chemotherapy for breast cancer

• Conditions: 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.; MedDRA version: 9.1Level: LLTClassification code 10029354Term: Neutropenia

• Registration Number: EUCTR2007-000394-36-LV
• Lead Sponsor: Mayne Pharma Plc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-13
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 279

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 concurrent anti-cancer therapy, including endocrine therapy, immunotherapy and monoclonal antibody therapy and any concurrent treatment with bisphosphonates unless the subject has been on a stable dose for four weeks prior to the first does of chemotherapy (Day 1 of Cycle 1);
4.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);
5.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);
6.Prior bone marrow or stem cell transplant;
7.Any known myeloid abnormality (to include a pre-malignant myeloid condition or malignant condition);
8.Subjects who, in the Investigator’s opinion, have had extensive prior radiotherapy to a significant area of the bone marrow potentially affecting myelopoiesis;
9.Co-existing active infection, or received systemic anti-infectives within 72 hours prior to the first dose of chemotherapy (Day 1 of Cycle 1);
10.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;
11.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;
12.Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures;
13.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);
14.Known hypersensitivity to E. coli-delivered products or docetaxel or other drugs formulated with polysorbate 80 or intolerance to doxorubicin;
15.Previously received any G-CSF;
16.Uncontrolled hypercalcaemia (>NCI CTCAE (Version 3.0) grade 1);
17.Second malignancy (except adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix);
18.Pregnant or breast-feeding women;
19.Concomitant treatment with lithium or lithium products.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified