Phase 1b Study of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
研究概览
简要总结
The primary objectives of this study are to evaluate the safety and tolerability of CS-7017 administered orally twice a day in combination with carboplatin and paclitaxel, and to assess the pharmacokinetics of CS-7017 in combination with carboplatin and paclitaxel.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed unresectable locally advanced or metastatic (stage IIIb or IV) non-small cell lung cancer (NSCLC)
- •No prior systemic therapy for NSCLC
- •Male or female ≥ 18 years of age
- •Anticipation of more than 3 months survival
- •Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤ 1
- •Adequate organ and bone marrow function
排除标准
- •Anticipation of need for a major surgical procedure or radiation therapy during the study
- •Remaining influence of previous therapies such as radiotherapy, surgery, immunotherapy within 4 weeks prior to start of study treatment
- •History of any of the following events within 6 months prior to start of study treatment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class ≥I congestive heart failure (CHF), cerebrovascular accident or cerebral infarction, pulmonary embolism, deep vein thrombosis, or other clinically significant thromboembolic event; clinically significant pulmonary disease (eg, severe chronic-obstructive pulmonary disease (COPD) or asthma)
- •Severe edema, ascites fluid, pericardial or pleural effusion or pericardial involvement with the tumor within 6 months prior to start of study treatment, or which require steroid therapy/ diuretic therapy
- •Subjects with brain metastasis (defined as untreated, symptomatic or requiring steroids or anticonvulsant medications to control associated symptoms)
- •Subjects with clinically significant active infection which requires antibiotic therapy, or who are hepatitis B surface antigen (HBs)- or hepatitis C virus (HCV)- or human immunodeficiency virus (HIV)- positive and receiving antiretroviral therapy
- •Subjects with malabsorption syndrome, chronic diarrhea (lasting over 4 weeks), inflammatory bowel disease, or partial bowel obstruction
- •Diabetes mellitus requiring insulin, or a history of poor serum glucose control with the use of non-insulin diabetes medications
- •Treatment with thiazolidinediones (TZDs) within 4 weeks prior to start of study treatment
- •History of a second malignancy, with the exception of in situ cervical cancer or adequately treated basal cell or squamous cell carcinoma of the skin
- •Poorly-controlled blood pressure as judged by the Investigator
研究组 & 干预措施
CS-7017+Carboplatin/Paclitaxel
Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4~6 cycles (1 cycle: 3 weeks)
Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL*min, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
Drug: Paclitaxel IV, 200mg/m^2, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
干预措施: CS-7017 (Drug)
CS-7017+Carboplatin/Paclitaxel
Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4~6 cycles (1 cycle: 3 weeks)
Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL*min, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
Drug: Paclitaxel IV, 200mg/m^2, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
干预措施: Carboplatin (Drug)
CS-7017+Carboplatin/Paclitaxel
Drug: CS-7017 from 0.25 mg twice a day (BID) to 0.50 mg BID for up to 4~6 cycles (1 cycle: 3 weeks)
Drug: Carboplatin IV, Area under the curve (AUC) of 6 mg/mL*min, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
Drug: Paclitaxel IV, 200mg/m^2, once every three weeks for up to 4~6 cycles (1 cycle: 3 weeks)
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
时间窗: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose
The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).
Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
时间窗: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose
The area under the concentration versus time curve during dosing interval (AUCtau) and up to the last quantifiable time (AUClast) of geometric means of CS-7017 are reported at selected cycles (C) and days (D).
Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
时间窗: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose
The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D).
Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
时间窗: Baseline to end of Cycle 1, with each treatment cycle being 3 weeks
Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug.
次要结局
- Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)(Baseline up to Week 18 postdose)
- CS-7017-Related Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group After Administration of CS-7017 and Carboplatin/Paclitaxel in Chemotherapy-naïve Participants With Stage IIIb/IV Non-small Cell Lung Cancer(Baseline to 30 days after last dose, up to approximately 1 year)