A Clinical Experience Trial to Detect the Plasma Paclitaxel Drug Concentration in Chinese Non -Small Cell Lung Cancer (NSCLC) Patients Treated With a Paclitaxel Plus Carboplatin (TC) Regimens, and Explore Individualized Treatment Using Pharmacokinetically-guided Dosing Strategy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Change of tumor sizes from baseline
研究概览
简要总结
By detecting the blood concentration of paclitaxel (PTX), Investigator assume this research can identify the individual differences of PTX pharmacokinetics (PK) parameters (TC>0.05 refers to the duration of paclitaxel plasma concentration above 0.05 µmol/L) in Chinese non-small cell lung cancer (NSCLC) patients, and find the correlation between PK results and PTX toxicities and Effectiveness, acquire the optimization method of PTX, and finally try to explore the individualized PTX pharmacokinetically-guided dosing strategy. Orally administer rosiglitazone, which is a substrate of CYP2C8 the same as paclitaxel, before chemotherapy injection. Detect the blood concentration of rosiglitazone, analyze the correlation of rosiglitazone pharmacokinetic parameter and paclitaxel exposure, and explore the effect of rosiglitazone as an in vivo probe of paclitaxel exposure.
- The variability of paclitaxel concentrations in the patient population dosed by body surface area (BSA), and the limitation of BSA-based dosing of paclitaxel.
- Verify that paclitaxel TC>0.05 is the most relevant predictor of haematological toxicity and clinical outcomes.
- Define a dosing algorithm based on paclitaxel TC>0.05 of paclitaxel and quantify its effect on both reducing toxicity and improving Effectiveness.
- The effect of using dose modification and administration of G-CSF based on toxicity determined by paclitaxel TC>0.05 measurement.
- Construct a trial outline with the aim of reducing grade 4 neutropenia toxicity and ensuring the clinical outcome by using individual dose adjustments based on the dosing algorithm.
- Detect the blood concentration of rosiglitazone after orally administration, explore the effect of rosiglitazone as an in vivo probe of paclitaxel exposure based on CYP2C8 activity. Attempt to establish a model to predict the paclitaxel exposure of patients base on rosiglitazone blood concentration before chemotherapy.
详细描述
Rosiglitazone probe:
Rosiglitazone: time point - at least 20 hours before the initiation of chemotherapy, orally administrate 2mg rosiglitazone.
Only before the first cycle chemotherapy.
Chemotherapy regimen:
Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection. 21 days per cycle; 6 cycles in total.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: 18 ~75 years
- •Pathology: Confirmed by pathology (histology or cytology) for advanced non-small cell lung cancer
- •Have indications of paclitaxel/carboplatin chemotherapy, suitable for paclitaxel chemotherapy (independent of clinical tumor stage or chemotherapy type or palliative chemotherapy lines)
- •At least one measurable tumor lesions (according to RECIST 1.1 criteria)
- •ECOG PS score: 0 to 2 points
- •Life expectancy: more than 3 months
- •Bone marrow reserve function is good, the function of organs (liver and kidney) is good, can satisfy the conditions of implementation chemotherapy. neutrophil count ≥1.5×109/l, platelet ≥75×109/l, hemoglobin >9g/dl, Total Bilirubin ≤1.5×ULN*, transaminase <2.5×ULN*, creatinine ≤1.5×ULN*,or creatinine clearance rate ≥45ml/min. ULR: Upper Limit Of Normal.
- •Sign the informed consent form; Compliance is good, can be followed up, willing to comply with the requirements of the study
排除标准
- •ECOG Performance Scores > 2 points
- •Organic disease (heart, liver, kidney disease etc), Active infection Organ transplantation immunosuppressive therapy, not capable to complete 4 - 6 cycles of paclitaxel / carboplatin chemotherapy.
- •Any other tumor history not cured in 3 years before this trial.
- •Bone marrow function or organs function not eligible for chemotherapy.
- •Diabetic patients currently receiving the standard anti- diabetes treatment.
研究组 & 干预措施
Paclitaxel and Carboplatin regimen
Paclitaxel: 175mg/m2, d1; Intravenous drip injection with 500ml N.S Carboplatin: AUC=5, d1; Intravenous drip injection with 500ml G.S Paclitaxel injection at first, followed with Carboplatin injection. 21 days per cycle; 6 cycles in total.
干预措施: Paclitaxel and Carboplatin regimen (Drug)
结局指标
主要结局
Change of tumor sizes from baseline
时间窗: baseline; 6 weeks; 12 weeks; 18 weeks; 24 weeks; 32 weeks; up to 3 years.
Object response rate (ORR): assess the ORR of paclitaxel/carboplatin chemotherapy according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
次要结局
- Area under the plasma concentration versus time curve (AUC) of rosiglitazone(3 hours after rosiglitazone administration)
- The duration of paclitaxel plasma concentration above 0.05 µmol/L (TC>0.05)(5min before paclitaxel administration; and 24 hours after.)
- progression free survival (months)(From date of consent form until the date of first documented progression, up to 36 months.)
- Overall survival (months)(From date of consent form until the date of death from any cause, up to 36 months.)
- Toxicities rate(day10, day21, day 31, day 42, day 52, day 63, day 73, day 84, day 94, day 105, day115 and day 126.)
研究者
Li Zhang, MD
Professor
Sun Yat-sen University