A Phase III, Randomized, Multicentric, Open-label, Equivalence Design Study to Compare theSafety and Efficacy of USV Pegfilgrastim and Neulasta®in Patients Receiving Doxorubicinand Docetaxel as a Combination Chemotherapy for Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 120
- 试验地点
- 8
- 主要终点
- Duration of severe neutropenia (DSN) during first chemotherapy cycle, defined as the number of days with grade 4 neutropenia with an ANC 0.5x109/L (500/mm3).
研究概览
简要总结
Phase III, randomized, multicentric, open-label, equivalence study, adult females diagnosed with breast cancer scheduled to undergo chemotherapy with doxorubicin and docetaxel will be enrolled. A total of 120 consenting patients who fulfil the eligibility criteria will be included into the study from 9 centres across India. Subjects will be randomized in 1:1 ratio to one of the two study treatment groups, stated below on Day 1 of the first chemotherapy cycle.
• Group I: USV PEG-Filgrastim (Test product) - 6 mg subcutaneous (SC) injection
• Group II: Neulasta® (Reference product) - 6 mg subcutaneous (SC) injection
Study drug will be administered by subcutaneous injection on Day 2 at least 24 hours after administration of chemotherapy.
All subjects will be provided information about the study and informed consent will be obtained before any screening procedure and enrolment into the study. There will be audio-video recording of consent process. Subjects will be enrolled in this study if they fulfil the eligibility criteria.
Chemotherapy will be repeated every 3-4 weeks and study evaluations for efficacy in this study will be for up to four cycles only. Subjects will be asked to visit the site 28 days after study drug administration for the 4th chemotherapy cycle or last chemotherapy cycle. In addition, there will be follow-up visits at the end of 3 months and 6 months (90 +/- 7 and 180 +/- 7 days, respectively, from the first dose of study drug) for the collection of blood sample for ANC only on 180 day visit and immunogenicity assessment on both of these visits.
Subjects completing the first cycle of chemotherapy will be evaluated for primary endpoint. Secondary endpoints will be evaluated as per the number of subjects completing each cycle
研究设计
- 研究类型
- Interventional
- 分配方式
- Permuted block randomization, fixed
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- Female
入选标准
- •1.Female ≥18 and ≤65 years of age; 2.Patient who has provided written informed consent;
- •Chemotherapy naive patient with documented high risk stage II, or stage III or stage IV breast cancer (classification according to American Joint Committee on Cancer-AJCC; 4.Patient scheduled to receive chemotherapy comprising of docetaxel (75 mg/m2) and doxorubicin (60mg/m2) for their breast cancer disease; 5.Estimated life expectancy more than 6 months;
- •ECOG Performance [Appendix 5] Status ≤ 2 as determined within 7 days prior to Day 1 of Cycle 1 of chemotherapy; 7.Adequate bone marrow function, as determined within 7 days prior to administration of chemotherapy on Day 1 of Cycle 1 and as indicated by: •Hb ≥9 g/dL (transfusion permitted during study); •ANC ≥1.5 x 109/L (≥1500/mm³); •Platelet count ≥100,000/μL (≥100 x 109/L).
- •Adequate renal and hepatic function, as determined within 7 days prior to administration of chemotherapy on Day 1 of Cycle 1 and as indicated by: •Creatinine <1.5 x Upper Limit of Normal (ULN); • Total bilirubin within normal reference range (unless elevation is known to be due to Gilbert’s disease); Patients must also meet one of the following criteria: •Alkaline phosphatise (ALP) within normal reference range and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <1.5 x ULN or •Alkaline phosphatase <2.5 x ULN and both AST and ALT<1.5 x ULN or •Alkaline phosphatase <5 x ULN and both AST and ALT within normal reference range.
排除标准
- •1.Previous therapy with any Granulocyte-Colony Stimulating Factor (G-CSF) and Pegfilgrastim preparation; 2.Patients with history of severe chronic neutropenia (congenital, cyclic or idiopathic); 3.Patients with history of chronic myeloid leukaemia or myelodysplastic syndrome; 4.Previous or concurrent malignancy except non-invasive non-melanomatous skin cancer, in-situ carcinoma of cervix, or other solid tumour treated curatively and without evidence of recurrence for at least 2 years prior to study entry; 5.Patient who require concurrent radiotherapy or have radiotherapy within the 4 weeks prior to the first dose of chemotherapy, except for localized spot radiotherapy for bone metastases (Day 1 of Cycle 1) 6.Patient who is having concurrent anti-cancer therapy, including endocrine therapy (with the exception of corticosteroids at doses ≤20 mg/day prednisolone or equivalent), immunotherapy, monoclonal antibody therapy and/or biological therapy; 7.Patient with chronic use of oral corticosteroids; 8.Concurrent treatment with bisphosphonates (unless the patient has been on a stable dose for four weeks prior to the first dose of chemotherapy [Day 1 of Cycle 1]); 9.Underlying neuropathy of grade 2 or higher; 10.Concurrent treatment with lithium; 11.Patients with prior bone marrow or stem cell transplantation; 12.Patients with leukocyte count more than 50 x 109/L; 13.Patients with cough, fever, dyspnoea in association with radiologic signs of pulmonary infiltrates at study entry; 14.Patient with clinically significant cardiac dysfunction at the time of screening, clinically significant findings on echocardiogram ( Ejection Fraction [EF] less than 50%) or a history of myocardial infarction or heart failure within 6 months preceding the first treatment cycle; 15.Brain metastases that are clinically symptomatic or being treated with steroids; 16.Patient with known hypersensitivity to E.
- •Coli proteins or any of the excipients used in the test products; 17.Patients with rare hereditary problems of fructose intolerance, sickle cell disorders 18.Patients with positive serology for HIV1/2, Hepatitis B virus and/or Hepatitis C virus; 19.Pregnant or breast feeding women.
- •Women of childbearing potential must have a negative urine pregnancy test within 7 days prior to Screening 20.Patient of childbearing potential unwilling to use a barrier method of contraception.
- •It is required that a barrier method of contraception be used (i.e. condom with spermicide or diaphragm with spermicide) by patients (or their partners) of childbearing potential regardless of whether a hormonal agent also is used as a method of contraception 21.Patient with known active drug addiction, including alcoholism; 22.Patient with systemic disease that may interfere with safety, compliance, response to the product under investigation or its evaluation; 23.Patient with co-existing active infection or have received systemic anti-infectives for the treatment of infection within 72 hours prior to the first dose of chemotherapy (Day 1 of Cycle 1); 24.Patient with symptomatic anaemia.
结局指标
主要结局
Duration of severe neutropenia (DSN) during first chemotherapy cycle, defined as the number of days with grade 4 neutropenia with an ANC 0.5x109/L (500/mm3).
时间窗: 2 weeks
次要结局
- Duration of DSN in each of chemotherapy cycles 2-4. ANC nadir during each chemotherapy cycle. Incidence of febrile neutropenia by clycle and acroos all cycles. Time to recovery of ANC from the second and subsequent chemotherapy cycles. Incidence of IV antibiotic administration and hospitalization due to febrile neutropenia. All cause mortality after start of study drug therapy. Incidence of documented infections and length of stay in ICU. Number of blood transfusion required.(25 weeks)