A Multicenter, Phase I/IIA, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose and To Evaluate the Safety Profile of CC-4047 Administered in Combination With Cisplatin and Etoposide in Patients With Extensive Disease Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 22
- 试验地点
- 6
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The purpose of this study is to determine the maximum tolerated dose and safety of CC-4047 (pomalidomide) given in combination with cisplatin and etoposide in patients with extensive disease small cell lung cancer.
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
- •signature of informed consent
- •Age >= 18
- •histologically or cytologically confirmed small cell lung cancer (SCLC)
- •extensive stage SCLC
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1 or 2
- •brain metastases that are asymptomatic and do not require steroid control
- •females of child bearing potential must use two forms of birth control
排除标准
- •pregnant or lactating females
- •prior use of cytotoxic chemotherapy
- •surgery within 14 days of study
- •radiation within 14 days of study
- •prior therapy with CC-4047 (pomalidomide), lenalidomide or thalidomide
- •concurrent use or anticipated use of anti-cancer agents
- •absolute neutrophil count (ANC) < 1500/mm^3
- •platelets < 100 x 10^3/µL
- •serum creatinine >2.5 mg/dL
- •serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) > 3.0 x upper limit of normal (ULN)
- •serum total bilirubin > 1.8 mg/dL
- •uncontrolled hypercalcemia
- •creatinine clearance <50 mL/min
- •uncontrolled hypertension
- •neuropathy >= grade 2
- •body mass index (BMI) >= 40
- •any other active invasive malignancy requiring treatment
- •known chronic infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)
- •inability or unwillingness to comply with birth control requirements
研究组 & 干预措施
Dose-finding arm: Pomalidomide + Cisplatin + Etoposide
Oral pomalidomide 1 mg - 5 mg daily (QD) for 14 consecutive days of a 21-day cycle, in combination with intravenous (IV) cisplatin 25 mg/m^2 and IV etoposide 100 mg/m^2 on Days 1, 2 and 3 of each cycle during the dose-finding phase (Treatment and Extension Periods; 6 cycles in total). Dose escalation followed a standard phase 1 3+3 design. Participants continuing took only their pomalidomide dose (monotherapy) for an additional 3-week Recovery Period (14 days of consecutive dosing followed by 7 days of no study medication). Participants continuing took oral pomalidomide 5 mg QD as monotherapy for 14 consecutive days of each 21-day cycle until disease progression in the Maintenance Phase.
干预措施: Pomalidomide (Drug)
Dose-finding arm: Pomalidomide + Cisplatin + Etoposide
Oral pomalidomide 1 mg - 5 mg daily (QD) for 14 consecutive days of a 21-day cycle, in combination with intravenous (IV) cisplatin 25 mg/m^2 and IV etoposide 100 mg/m^2 on Days 1, 2 and 3 of each cycle during the dose-finding phase (Treatment and Extension Periods; 6 cycles in total). Dose escalation followed a standard phase 1 3+3 design. Participants continuing took only their pomalidomide dose (monotherapy) for an additional 3-week Recovery Period (14 days of consecutive dosing followed by 7 days of no study medication). Participants continuing took oral pomalidomide 5 mg QD as monotherapy for 14 consecutive days of each 21-day cycle until disease progression in the Maintenance Phase.
干预措施: Cisplatin (Drug)
Dose-finding arm: Pomalidomide + Cisplatin + Etoposide
Oral pomalidomide 1 mg - 5 mg daily (QD) for 14 consecutive days of a 21-day cycle, in combination with intravenous (IV) cisplatin 25 mg/m^2 and IV etoposide 100 mg/m^2 on Days 1, 2 and 3 of each cycle during the dose-finding phase (Treatment and Extension Periods; 6 cycles in total). Dose escalation followed a standard phase 1 3+3 design. Participants continuing took only their pomalidomide dose (monotherapy) for an additional 3-week Recovery Period (14 days of consecutive dosing followed by 7 days of no study medication). Participants continuing took oral pomalidomide 5 mg QD as monotherapy for 14 consecutive days of each 21-day cycle until disease progression in the Maintenance Phase.
干预措施: Etoposide (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Cycle 1 (21 days)
The MTD was defined as the highest dose level at which no more than 1 in 6 participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle of treatment. The MTD Phase included the Treatment period (Cycle 1: Identification of the MTD) and the Extension period (Cycles 2 to 6: Confirmation of Safety of the MTD). (See Secondary Outcome Measure 2 for data on DLTs.)
次要结局
- Number of Participants With Dose Limiting Toxicities (DLTs) During the MTD Phase(Cycles 1 - 6 (21-day cycles))
- Overall Survival(From enrollment through study termination (approximately 35 months))
- Tumor Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST)(Cycles 1 -6 (21-day cycles))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the Recovery Period or Maintenance (Monotherapy) Phase(Cycle 7 to discontinuation (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide during Maintenance Phase was 5.0 (1.1, 36.0).)
- Duration of Response(From first Partial Response (PR) or Complete Response (CR) to disease progression (maximum of 19.4 weeks))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) During the MTD (Combination Treatment) Phase(Cycles 1-6 (21-day cycles). Median (full range) duration of exposure (in weeks) to pomalidomide (MTD Phase): 1 mg, 17.9 (1.0, 20.3); 3 mg, 17.0 (16.9, 22.0); 4 mg, 14.0 (0.7, 22.0); 5 mg, 13.0 (2.0, 22.1). Cisplatin and etoposide: 15.3 (0.4, 20.6).)