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 regimen 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.
- Registration Number
- EUCTR2007-000394-36-HU
- Lead Sponsor
- Mayne Pharma Plc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 279
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 refernce 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
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
- Primary Outcome Measures
Name Time Method Main Objective: To demonstrate the therapeutic equivalence of PLIVA/Mayne filgrastim to Neupogen;Secondary Objective: To compare the efficacy, safety and tolerability of PLIVA/Mayne filgrastim and Neupogen.<br>To compare the immunogenicity of PLIVA/Mayne filgrastim and Neupogen.;Primary end point(s): The primary endpoint is DSN (in days) (ANC<0.5 x 10 9/L) and body temperature of =38.5 °C
- Secondary Outcome Measures
Name Time Method