A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL147 (SAR245408) in Combination With Paclitaxel and Carboplatin in Subjects With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 175 mg/m2) and carboplatin in subjects with advanced solid tumors
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of XL147 in combination with paclitaxel and carboplatin in adults with solid tumors. XL147 is a new chemical entity that inhibits PI3 Kinase. Inactivation of PI3K has been shown to inhibit growth and induce apoptosis (programmed cell death) in tumor cells. In clinical practice, the combination of paclitaxel and carboplatin is an accepted treatment regimen for various solid tumors, including ovarian cancer, endometrial cancer and non-small cell lung cancer (NSCLC).
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
- •Confirmed diagnosis of:
- •Advanced solid tumor that is no longer responding to therapies OR
- •Advanced or recurrent endometrial carcinoma OR
- •Advanced or recurrent ovarian carcinoma OR
- •Unresectable (Stage IIIB or IV) NSCLC
- •ECOG Performance Status 0-1 (ECOG status of 2 may be considered following discussion and agreement with sponsor)
- •Adequate organ and bone marrow function as defined by hematological and serum chemistry limits
- •At least 18 years old
- •Both men and women must practice adequate contraception
- •Informed consent
排除标准
- •Restriction of some therapies/medications within specific timeframes prior to enrollment and during the study including prior therapy with PI3K, AKT, or mTOR inhibitors, cytotoxic chemotherapy, biologic agents, nitrosoureas or mitomycin C, small-molecule kinase inhibitors, non-cytotoxic hormonal agents
- •Known allergy or hypersensitivity to any of the components of the treatment formulations
- •Taking oral corticosteroids chronically or > 1 mg/day warfarin
- •Not recovered from the toxic effects of prior therapy
- •History of diabetes mellitus.
- •Uncontrolled intercurrent illness
- •Pregnant or breastfeeding
- •Congestive heart failure, unstable angina, or a myocardial infarction within 3 months of entering the study.
- •HIV positive
- •Diagnosis of another malignancy may exclude subject from study
研究组 & 干预措施
1
干预措施: XL147 (SAR245408), (Drug)
1
干预措施: paclitaxel (Drug)
1
干预措施: carboplatin (Drug)
结局指标
主要结局
To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 175 mg/m2) and carboplatin in subjects with advanced solid tumors
时间窗: Assessed at periodic visits
To evaluate the safety, tolerability, and MTD of XL147 administered in combination with paclitaxel (at doses up to 225 mg/m2) and carboplatin in subjects with NSCLC
时间窗: Assessed at periodic visits
次要结局
- To investigate the relationship between selected biomarkers and efficacy and safety outcomes(Assessed at periodic visits)
- To assess plasma pharmacokinetics (PK) of XL147, paclitaxel, and carboplatin when used in combination(Assessed at periodic visits)
- To evaluate preliminary antitumor activity of XL147 in combination with carboplatin and paclitaxel(Assessed at periodic visits)