A PHASE 1B, MULTI-CENTER, OPEN-LABEL STUDY OF THE MTOR KINASE INHIBITOR CC-223 IN COMBINATION WITH ERLOTINIB OR ORAL AZACITIDINE IN ADVANCED NON-SMALL CELL LUNG CANCER
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Celgene
- 入组人数
- 76
- 试验地点
- 9
- 主要终点
- Adverse events
研究概览
简要总结
The main purpose of this first study combining an investigational dual mTOR inhibitor, CC-223, with other agents (erlotinib or the investigational agent, oral azacitidine) is to establish a maximum tolerated dose level for each combination in order to evaluate their effects in future clinical trials for advanced non-small cell lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Men and women, 18 years or older, with histologically or cytologically-confirmed, Stage IIIB/IV Non-Small Cell Lung Cancer with tumor progression following at least one prior treatment regimen (either chemotherapy or an Epidermal Growth Factor Receptor inhibitor) for advanced disease. There is no restriction on the number of prior treatment regimens allowed.
- •Eastern Cooperative Oncology Group Performance Score of 0 to
- •Adequate organ function.
- •Adequate contraception (if appropriate).
- •Consent to retrieve archival tumor tissue.
- •Consent to repeated tumor biopsy (dose expansion phase).
排除标准
- •Prior systemic cancer-directed treatments or investigational drugs within 4 weeks or 5 half lives, whichever is shorter except erlotinib which may be continued with intervention in subjects allocated in Arm A.
- •Symptomatic central nervous system metastases.
- •Acute or chronic pancreatitis.
- •Persistent diarrhea or malabsorption > Grade 2, despite medical management.
- •Impaired cardiac function or significant cardiac disease.
- •Diabetes on active treatment, fasting blood glucose > 126 mg/dL, HbA1c > 6.5%.
- •Known Human Immunodeficiency Virus, chronic hepatitis B or C infection.
- •Prior treatment with an investigational dual TORC1/TORC2, PI3K, or Akt inhibitor. Prior treatment with rapalogs is allowed.
- •Major surgery < 2 weeks prior to starting study drugs. No specific wash out is required for radiotherapy. Subjects must have recovered from any effects of recent therapy that might confound the safety evaluation of study drug.
- •Pregnant or breastfeeding, inadequate contraception.
- •History of concurrent second malignancies requiring ongoing systemic treatment.
研究组 & 干预措施
CC-223/erlotinib concurrent
Cohorts will receive escalating continuous daily doses (15 mg and 30 mg) of CC-223 in capsules concurrently with at least two different daily dose levels of erlotinib tablets (100 mg and 150 mg) in 28-day cycles.
干预措施: CC-223, erlotinib (Drug)
CC-223/oral azacitidine concurrent
Cohorts will receive escalating continuous daily doses of CC-223 (15 mg and 30 mg) with one or more dose levels of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Day 1 to 21 of each 28-day cycle.
干预措施: CC-223, oral azacitidine (Drug)
CC-223/oral azacitidine sequential
Cohorts will receive escalating continuous daily dose levels of CC-223 (15 mg and 30 mg) administered on Days 8 through 28 sequentially with one or more dose levels of of oral azacitidine (200 mg or 300 mg, as two or three 100 mg tablets) administered on Days 1 to 7 of each 28-day cycle
干预措施: CC-223, oral azacitidine (Drug)
结局指标
主要结局
Adverse events
时间窗: Up to 24 months
Number of participants with adverse events
PK-Cmax
时间窗: Up to 15 months
Pk-Maximum observed concentration in plasma (Cmax)
PK-T1/2
时间窗: Up to 15 months
PK-Terminal half-life (T1/2)
PK-Tmax
时间窗: Up to 15 months
PK-Time to maximum concentration (Tmax)
MTD
时间窗: Up to 24 months
Maximum tolerated dose (MTD)
PK-AUC
时间窗: Up to 15 months
Area under the plasma concentration-time curve (AUC)
PK-Vz/F
时间窗: Up to 15 months
PK-Apparent volume of distribution (Vz/F)
PK-CL/F
时间窗: Up to 15 months
PK-Apparent total body clearance (CL/F)
次要结局
- CC-223 metabolite, M1(Up to 9 months)
- Tumor Response Rate(Up to 24 months)
- mTORC1 and mTORC2 pathway biomarkers(Up to 15 months.)
- Number of participants surviving without tumor progression(Up to 24 months)