A Multicenter, randomized, single-blind, 2-way crossover, Pivotal Pharmacokinetic Bioequivalence Study Comparing Generic to Reference Liposome-Encapsulated Doxorubicin Hydrochloride in Subjects with Epithelial Ovarian Carcinoma Who Have Failed Platinum-Based Chemotherapy
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- TOLMAR Inc
- 入组人数
- 60
- 试验地点
- 10
- 主要终点
- formulation in subjects with progressive or recurrent epithelial ovarian cancer.
研究概览
简要总结
This is a multicenter,randomized, single-blind, 2-way crossover, PK BE study in subjects with epithelialovarian carcinoma whose disease has progressed or recurred after platinum-basedchemotherapy.
This study is designedto evaluate the PK parameters and safety of DOXOrubicin and TOLMAR formulationat the standard 50 mg/m2 dose for patients with ovarian cancer. Cohort1 will receive DOXOrubicin on Cycle 1/Day 0 and TOLMAR formulation on Cycle2/Day 0. Cohort 2 will receive TOLMAR formulation on Cycle 1/Day 0 and DOXOrubicinon Cycle 2/Day 0.
Subjects, thebioanalytical laboratory personnel, and TOLMAR personnel performing data analysiswill remain blinded throughout the study with regard to subject treatment (ie,cohort assignment). Investigators will have knowledge of subject treatmentassignment to verify that subjects received their correct treatment as pertheir randomized assignment.
The dose of DoxorubicinHydrochloride for individual subject will be calculated according to bodysurface area (Calculated by Mosteller formula).
A total of twenty-six(26) blood samples, each of 10 mL from each patient will be collected duringstudy for PK assessment.
On Day 0 of Dosingcycles 1 and 2:
The pre-dose bloodsample of 10 mL will be drawn at up to 30 minutes prior to start of infusion.
The post-dose bloodsamples of 10 mL each will be drawn at 0.50, 1.00 (i.e. at end of infusion),2.00, 3.00, 4.00, 8.00, 24.00, 48.00, 96.00, 168.00, 240.00 and 336.00 hoursafter start time of intravenous Infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- Female
入选标准
- •1.Female between 18 and 75 years of age, inclusive.
- •2.Histologically proven epithelial ovarian carcinoma.
- •3.Documented progressive or recurrent disease after treatment with platinum based chemotherapy.
- •4.Able and clinically indicated to receive liposomal doxorubicin HCl, as specified in the DOXOrubicin Package Insert for subjects with ovarian cancer, without exceeding a lifetime cumulative dosage of 450 mg/m2 (See Section 7.3.1 for rationale).
- •Prior use of conventional or liposomal doxorubicin formulations, in addition to the use of other anthracyclines or anthracenediones should be included in calculations of total lifetime cumulative dose.
- •5.Able and clinically indicated to receive the recommended minimum 4 courses of liposomal doxorubicin HCl either during participation in this study, including infusions prior to enrolling in this study or after completing study participation 6.Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 (See Appendix 14.1).
- •Any subject who experiences deterioration in ECOG status to 4 during the study should discontinue participation in the study.
- •7.Life expectancy of > 180 days.
- •8.Acceptable hematology status: a.Hemoglobin ≥ 9 g/dL b.Absolute neutrophil count (ANC) ≥ 1500 cells/µL c.Platelet count ≥ 75,000 cells/µL 9.Acceptable liver function: a.Alanine aminotransferase (ALT) ≤ 2X upper limit of normal (ULN) b.Aspartate aminotransferase (AST) ≤ 2X ULN c.Bilirubin < 1.2 mg/dL d.Alkaline phosphatase ≤ 2X ULN 10.Acceptable kidney function a.Creatinine ≤ 2X ULN or b.Creatinine clearance ≥ 60 mL/minute 11.Cardiac ejection fraction ≥ 50% by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan within 14 days prior to first dose of Investigational Product.
- •12.If of childbearing potential, must agree to use adequate contraception (eg, hormonal, chemical, double-barrier, or abstinence) while on study and for 3 months after study participation is discontinued.
- •13.Willing and able to provide written informed consent prior to any study-related activities being performed.
排除标准
- •Exclusion Criteria: 1.Received liposomal doxorubicin HCl in the past and had a required dose reduction to below 50 mg/m2, or whose disease has progressed or recurred after treatment with liposomal doxorubicin.
- •2.Received previous chemotherapy less than 4 weeks prior to dosing of Investigational Product.
- •3.Recent (6 month) history of myocardial infarction or severe arrhythmias prior to dosing of Investigational Product (See DOXOrubicin Package Insert).
- •4.History of major cardiac (New York Heart Association [NYHA] Type III or IV), liver, or kidney disease.
- •5.Received any prior mediastinal irradiation (as cardiac toxicity may occur at lower cumulative doses).
- •6.Receipt of trastuzumab within 24 weeks prior to dosing of Investigational Product and during the study (DOXOrubicin Hydrochloride Injection Package Insert).
- •7.Receipt of cyclophosphamide, calcium channel blockers, and other potential cardiotoxic drugs for 2 weeks prior to dosing of Investigational Product, and during the study (See DOXOrubicin Package Insert and anthracycline package insert).
- •9.Known hypersensitivity, idiosyncratic, or allergic reactions to conventional or liposomal formulations of doxorubicin, anthracycline therapy or to any of their components.
- •10.Pregnant or breastfeeding.
- •11.Active opportunistic infection with mycobacteria, cytomegalovirus, toxoplasma, Pneumocystis carinii, or other microorganism.
- •12.Presence or recent history (within the last 2 months) of clinically significant ascites requiring intervention (eg, paracentesis).
- •Note: stable dose of diuretics will be permitted.
- •13.Known central nervous system metastasis.
- •14.Major surgical procedure (including periodontal) within 28 days of first dose of Investigational Product.
- •15.Surgical or other non-healing wounds.
- •16.Exposure to any investigational agent within 28 days prior to first dose of Investigational Product.
- •17.History of other malignancies in the last 5 years.
- •Potential subjects with prior history of in situ cancer or basal or squamous cell skin cancer are eligible.
- •Potential subjects with other malignancies that were cured with definitive primary therapy alone (eg, surgery) and who have been continuously free of the previous disease for 1 year are also eligible upon Sponsor approval.
- •18.Severe or life-threatening infection, including known past medical history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS).
- •19.Has not recovered to Grade 0 or 1 toxicity from previous anticancer treatments or previous investigational agents.
- •Exceptions are alopecia (any grade is acceptable), fatigue (Grade 2 is acceptable), and peripheral neuropathy (stable Grade 2 is acceptable) (Per National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE], v4.03).
- •20.Uncontrolled diabetes mellitus.
- •21.Any other medical condition or serious intercurrent illness that, in the opinion of the Investigator, may make it undesirable for the subject to participate in the study including but not limited to cirrhosis or psychiatric illness/social situations that would limit adherence to study requirements.
- •22.Any other condition(s) which could significantly interfere with Protocol compliance including, but not limited to, dementia, psychosis, cognitive impairment, altered mental status, or other major psychiatric disorder.
- •24.(INDIA) Donation and/or loss of 350 ml (1 unit) of blood within 90 days of Cycle 1 Day
- •26.(INDIA) Presence identified during screening laboratory tests of malaria, syphilis or HIV.
结局指标
主要结局
formulation in subjects with progressive or recurrent epithelial ovarian cancer.
时间窗: Up to 30 minutes prior dosing, During infusion: 0.50 hr; end of infusion: 1.00 hr and after end of infusion: 2.00, 3.00, 4.00, 8.00, 24.00, 48.00, 96.00, 168.00, 240.00, 336.00 hr
To compare the PK parameters of DOXOrubicin and TOLMAR
时间窗: Up to 30 minutes prior dosing, During infusion: 0.50 hr; end of infusion: 1.00 hr and after end of infusion: 2.00, 3.00, 4.00, 8.00, 24.00, 48.00, 96.00, 168.00, 240.00, 336.00 hr
次要结局
- To assess safety and tolerability of DOXOrubicin and TOLMAR(Formulation.)