A multicenter, open label, randomized, balanced, two-treatment, three-period, three-sequence, single dose, replicate cross-over bioequivalence study of Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL (50 mg/m2 dose) of Sun Pharmaceutical Industries Ltd., India with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion of Janssen Pharmaceutica NV, Belgium in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients under fed (standardized light meal) condition.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 15
- 主要终点
- To assess the bioequivalence of the test product (Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL) relative to that of reference product Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion) in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients.
研究概览
简要总结
A multicenter, open label, randomized, balanced, two-treatment, three-period, three-sequence, single dose, replicate cross-over bioequivalence study of Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL (50 mg/m2 dose) of Sun Pharmaceutical Industries Ltd., India with that of Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion of Janssen Pharmaceutica NV in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients under fed (standardized light meal) condition.
The primary Objective of study is to assess the bioequivalence of the test product (Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL) relative to that of reference product Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion) in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients.
90% confidence interval of the geometric mean ratio (GMR) of Cmax of the test and reference product for unencapsulated doxorubicin and encapsulated doxorubicin should be between 80.00% and 125.00% for ln-transformed data.
90% confidence interval of the geometric mean ratio (GMR) of AUC0-49 and AUC49-t of the test and reference product for encapsulated doxorubicin should be between 80.00% and 125.00%
for ln-transformed data.
“This study will be managed by CBCC Global research in agreement withSponsor (Sun Pharmaceutical Industries Limited)â€.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- Female
入选标准
- •Willing and able to provide voluntary informed consent and to follow the protocol requirements.
- •Female patients between 18 and 75 years of age, both inclusive and having Body mass index BMI greater or equal to 17.00 calculated as weight in kg per height in m
- •Histopathologically confirmed ovarian cancer or breast cancer
- •Patients with stable advanced ovarian cancer requiring Doxorubicin and who have failed a first-line platinum-based chemotherapy regimen.
- •Patients with stable metastatic breast cancer requiring Doxorubicin as monotherapy
- •Able and clinically indicated to receive the recommended minimum 3 cycles of liposomal doxorubicin HCl.
- •Eastern Cooperative Oncology Group ECOG performance status of less or equal to
- •nLife expectancy of greater to 180 days based on clinical evaluation by the investigator at the time of screening.
- •Acceptable hematology status: a.
- •Hemoglobin greater or equal to 9.0 g per dL b.
- •Absolute neutrophil count ANC greater or equal to 1500 cells per µL c.
- •Platelet count greater or equal to 1,00,000 cells per µL
- •Acceptable liver function: a.
- •Alanine aminotransferase ALT less or equal to 2.5 x ULN b.
- •Total Bilirubin less than 1.2 mg per dL d.
- •Patients with Creatinine clearance greater or equal to 60 mL per minute
- •Left Ventricular ejection fraction greater or equal to 50 percent by echocardiogram ECHO during screening.
- •Patients with negative serum pregnancy test at screening and negative urine pregnancy test at Day
- •Women of child bearing potential, defined as women physiologically capable of becoming pregnant, unless they must agree to use effective method of contraception during dosing and up to six months after the last dose of study drug of the investigational product practicing two acceptable methods of contraception.
- •Acceptable methods of contraception are: a.
- •Intrauterine device IUD or intrauterine system IUD or IUS b.
- •Double barrier method of contraception Condom and occlusive cap or condom and spermicidal agent c.
- •Male sterilization at least 6 months prior to the screening, should be the sole male partner for that patient d.
- •Female sterilization surgical bilateral oophorectomy or tubal ligation at least 6 weeks prior to study participation e.
- •No history of addiction to any recreational drug or drug dependence or alcohol addiction.
排除标准
- •Known hypersensitivity or contraindication including anaphylaxis to conventional or liposomal formulations of doxorubicin, anthracycline therapy, peanut or soya or to any of their components
- •Patients with prior doxorubicin exposure that would result in a total lifetime exposure of more than 450 mg/m2 (Prior use of other anthracyclines or anthracenodiones should be included in calculations of total cumulative dosage)
- •Received previous chemotherapy within 4 weeks of dosing of Investigational Product.
- •Patients with impaired cardiac function including any of the following conditions within 6 months prior to screening: a.
- •Unstable angina b.
- •QTc prolongation or other significant ECG abnormalities.
- •Coronary artery bypass graft surgery.
- •Symptomatic peripheral vascular disease.
- •Myocardial infarction f.
- •NYHA class II-IV heart failure g.
- •Severe uncontrolled ventricular arrhythmias h.
- •Clinically significant pericardial disease i.
- •Electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
- •Received any prior mediastinal irradiation (as cardiac toxicity may occur at cumulative doses lower than 450mg/m2).
- •Receipt of trastuzumab within 24 weeks prior to dosing of Investigational Product and during the study.
- •Patients taking inducers and inhibitors of CYP3A4, CYP2D6 or P-gp
- •Pregnant or lactating women
- •Patients with uncontrolled metabolic disorders including diabetes mellitus (HbA1c greater or equal to 9 %) at screening.
- •Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism if under treatment with myelotoxic drugs.
- •Known central nervous system metastasis
- •Surgical or other non-healing wounds.
- •History of other malignancies in the last 5 years.
- •(except in situ cancer or basal or squamous cell skin cancer)
- •Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents.
- •Exceptions are alopecia (any grade is acceptable), Hemoglobin greater or equal to 9.0 g/dL and fatigue (Grade 2 is acceptable) (Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], V5.0).
- •Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the patient to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
- •Participation in any clinical study within 90 days before the first dose of Investigational Product.
- •Donation and/or loss of greater or equal to 350 mL (1 unit) of blood within 90 days before the first dose of Investigational Product.
- •Patients with pre-existing motor or sensory neurotoxicity of a severity greater or equal to grade 2 by NCI criteria.
- •Patients with history of other clinically significant concomitant disease including gastrointestinal, pulmonary, endocrine, immunologic, dermatologic, neurologic, psychological, musculoskeletal, cardiac, liver or renal disease.
- •Patient with uncontrolled hypertension (systolic blood pressure [BP] >180 or diastolic BP >100 mm Hg) with or without antihypertensive treatment.
- •Patient with history of cerebrovascular accident (CVA) within 6 months or venous thrombosis within 12 weeks.
结局指标
主要结局
To assess the bioequivalence of the test product (Doxorubicin Hydrochloride Pegylated Liposome Injection 2mg/mL) relative to that of reference product Caelyx® 2mg/mL [Doxorubicin Hydrochloride (Pegylated Liposomal)] concentrate for solution for infusion) in stable advanced ovarian cancer patients who have failed a first-line platinum based chemotherapy regimen or stable metastatic breast cancer patients.
时间窗: A total of 18 PK blood samples will be collected in each period of the study. The pre-infusion blood sample (0.00) will be drawn within one hour prior to the scheduled infusion time and at 0.250, 0.500, 0.750, 1.000, 1.083, 1.250, 1.500, 2.000, 4.000, 6.000, 9.000, 25.000, 49.000, 97.000, 169.000, 241.000 and 337.000 hours after start of intravenous Infusion.
次要结局
- To monitor the adverse events and to ensure the safety of patients.(Safety assessment will be carried out during screening, on day 0, 1, 2, 3, 5, 8, 11 and 15 in period 01 and on day 28, 29, 30, 31, 33, 36, 39 and 43 in period 02 and on day 56, 57, 58 ,59, 61, 64, 67 and 71 in period 03 and during end of study.)