NCT02364362已完成1 期
Docetaxel Plus Famitinib Versus Docetaxel Plus Placebo in Patients With Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of famitinib in combination with standard-dose docetaxel(60 mg/m^2)
研究概览
简要总结
Famitinib is a tyrosin-inhibitor agent targeting at c-Kit, VEGFR2, PDGFR, VEGFR3, Flt1 and Flt3. Phase I study has shown that the toxicity is manageable.
This study assessed the safety and maximum tolerated dose of continuous daily treatment with Famitinib plus docetaxel (60 mg/m^2, every 3 weeks) in patients with Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC) to determine the recommended dose for the Phase II trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age:18-70 years;
- •ECOG PS (Eastern Cooperative Oncology Group Performance Status)of 0 or 1;
- •Life expectancy of at least 12 weeks;
- •Histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of stage IIIB or IV or recurrent NSCLC;
- •Relapse or failure of one first line prior platinum-based chemotherapy;EGFR mutation type previously treated with platinum-based chemotherapy and EGFR inhibitors;
- •At least one target tumour lesion that has not been irradiated within the past 3 months and that can accurately be measured ,according to RECIST 1.1;
- •Participants have adequate organ and marrow function as defined below:
- •Hemoglobin ≥ 90g/L ( no blood transfusion in 2 weeks)
- •Absolute neutrophil count (ANC) ≥ 1.5×10^9/L
- •Platelets(PLT)≥ 100×10^9/L
- •Bilirubin < 1.25×ULN(Upper Limit Of Normal)
- •ALT < 2.5×ULN; ALT < 5×ULN ( If have liver metastases)
- •AST < 2.5×ULN; AST < 5×ULN ( If have liver metastases)
- •Serum creatinine < 1.25×ULN, and endogenous Cr clearance > 45 ml/min(Cockcroft-Gault Formula)
- •Cholesterol ≤ 1.5×ULN and triglyceride≤ 2.5×ULN
- •Left ventricular ejection fraction(LVEF): ≥ LLN(Lower Limit Of Normal) by Color Doppler Ultrasonography
- •Female: Child bearing potential, a negative urine or serum pregnancy test result 7 days before initiating famitinib.All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article. Male: All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 8 weeks after the last dose of test article;
- •Patient has given written informed consent.
排除标准
- •More than one chemotherapy treatment regimen (except,either neoadjuvant or adjuvant or neoadjuvant plus adjuvant) for advanced and/or metastatic or recurrent NSCLC;
- •Previous therapy with other VEGFR inhibitors (including sunitinib,sorafenib,pazopanib,axitinib,other than bevacizumab) or docetaxel for treatment of NSCLC;
- •Radiographical evidence of cavitary or necrotic tumours;
- •Centrally located tumours with radiographical evidence (CT or MRI) of local invasion of major blood vessels;
- •Pre-existing ascites and/or clinically significant pleural effusion;
- •Pulmonary hemorrhage/ bleeding event ≥ CTCAE gr. 2 before initiating investigational drugs;
- •History of clinically significant haemoptysis within the past 3 months（24h >half teaspoon）;
- •Current peripheral neuropathy greater than CTCAE grade 2;
- •Other malignancy within the past 3 years other than basal cell skin cancer, or carcinoma in situ of the cervix;
- •Active brain metastases (such as stable time ≤ 4 weeks,no radiotherapy treatment,any symptoms,or seizures treatment needing) or leptomeningeal disease.;
- •Treatment with other investigational drugs or other anti-cancer therapy, or treatment in another clinical trial within the past 4 weeks before start of therapy or concomitantly with this trial;
- •Persistence of clinically relevant therapy related toxicities from previous chemotherapy and/or radiotherapy;
- •Treatment with cytotoxic drugs, radiotherapy(except extremities and brain) , immunotherapy , monoclonal antibody, or TKI inhibitor therapy within the past 4 weeks, being previous anti-cancer treatment interval ≤ 4 weeks.;
- •Patients with hypertension using combination therapy (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg). Patients with unstable angina, myocardial ischemia or myocardial infarction in the past 6 months, congestive heart failure>NYHA II,and arrhythmia (including QTcF interval ≥ 450ms for male and 470ms for female);
- •Urine protein ≥ + + and confirmed the 24-hour urinary protein>1.0 g;
- •History of major thrombotic or clinically relevant major bleeding event in the past 6 months，and known inherited predisposition to bleeding or thrombosis;
- •PT or APTT bias from normal range≥50%;
- •Application of anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogues;If the prothrombin time international normalized ratio (INR) ≤ 1.5, with the purpose of prevention, the use of small doses of warfarin (1mg orally, once daily) ， low-dose aspirin (less than 100mg daily) is allowed;
- •Preexisting thyroid dysfunction, even using medical therapy, thyroid function cannot maintain in the normal range;
- •Diabetes mellitus can not controlled with hypoglycemic agent;
- •Active or chronic hepatitis C and/or B infection with liver dysfunction;
- •History of immunodeficiency disease, concurrent acquired or congenital immunodeficiency,or history of organ transplantation;
- •Serious infections requiring systemic antibiotic therapy;
- •Variety of factors that affect the oral medication (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction);
- •Significant weight loss (>10 %) within the past 6 months;
- •Pregnancy , breast feeding or child bearing potential, a positive urine or serum pregnancy test result 7 days before initiating famitinib;
- •Active alcohol or drug abuse;
- •Any contraindications for therapy with docetaxel；History of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80 (Tween 80)；Hypersensitivity to famitinib and/or the excipients of the trial drugs；Hypersensitivity to contrast media;
- •Psychological, familial, sociological, or geographical factors potentially hampering compliance with the study protocol and follow-up schedule;
- •Patients unable to comply with the protocol;
- •Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study.
研究组 & 干预措施
Famitinib + docetaxel
Experimental
Low, medium and high dose of famitinib and 60 mg/m^2 docetaxel every 3 weeks
干预措施: famitinib L + docetaxel (Drug)
Famitinib + docetaxel
Experimental
Low, medium and high dose of famitinib and 60 mg/m^2 docetaxel every 3 weeks
干预措施: famitinib M + docetaxel (Drug)
Famitinib + docetaxel
Experimental
Low, medium and high dose of famitinib and 60 mg/m^2 docetaxel every 3 weeks
干预措施: famitinib H + docetaxel (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of famitinib in combination with standard-dose docetaxel(60 mg/m^2)
时间窗: 3 weeks
MTD was defined as the highest dose at which incidence of dose-limiting toxicities(DLTs) in Cyle 1 was ≤33.3%(0/3,1/6,2/6)
次要结局
- Incidences of Adverse Events according to Common Toxicity Criteria (CTC version 4.0) associated with increasing doses of famitinib(1 years)
- Pharmacokinetics-AUC(6 weeks)
- Pharmacokinetics-Cmax(6 weeks)
- Pharmacokinetics-t1/2(6 weeks)
- Pharmacokinetics-Tmax(6 weeks)
- Objective Response Rate (ORR)(6 weeks)
- Progress free survival (PFS)(1 years)
研究者
研究点 (1)
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