Chloroquine as an Anti-autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients: A Phase 1 Trial
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 5
- 试验地点
- 4
- 主要终点
- To determine the toxicity of adding chloroquine in escalating doses in SCLC patients: to standard dose cisplatin-etoposide in extensive disease SCLC; to standard dose concurrent radiotherapy and cisplatin-etoposide in limited disease SCLC
研究概览
简要总结
Chloroquine might very well be able to increase overall survival in small cell lung cancer by sensitizing cells resistant to chemotherapy and radiotherapy.
详细描述
Tumor hypoxia is a well-known factor negatively influencing outcome in many solid tumors, including small cell lung cancer. Hypoxic cells are more radio-resistant, more chemo-resistant and more prone to develop distant metastases than normoxic cells.
One of the mechanisms responsible for survival of these therapy-resistant hypoxic cells is (macro-)autophagy: a phenomenon in which cells provide themselves with energy (ATP) by digesting their own cell-organelles. Chloroquine is a potent blocker of autophagy and has been demonstrated in a lab setting to dramatically enhance tumor response to radiotherapy, chemotherapy and even anti-hormonal therapy.
Thus, chloroquine might very well be able to increase overall survival in small cell lung cancer by sensitizing cells resistant to chemotherapy and radiotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed ''extensive disease'' (Stage T0-4 N0-3 M1) small cell lung cancer
- •At least one measurable disease site, defined as lesion of ≥ 1 cm unidimensionally on CT-scan.
- •WHO performance status 0-2
- •Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l.
- •Calculated creatinine clearance at least 60 ml/min
- •Adequate hepatic function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution; ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution (in case of liver metastases ≤ 5 x ULN for the institution)
- •No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC.
- •Life expectancy more than 6 months
- •Willing and able to comply with the study prescriptions
- •18 years or older
- •Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study
- •Ability to give and having given written informed consent before patient registration
- •No mixed pathology, e.g. non-small cell plus small cell cancer
- •No recent (< 3 months) severe cardiac disease (NYHA class >1) (congestive heart failure, infarction)
- •No history of cardiac arrythmia (multifocal premature ventricular contractions, uncontrolled atrial fibrillation, bigeminy, trigeminy, ventricular tachycardia) which is symptomatic and requiring treatment (CTC AE 4.0), or asymptomatic sustained ventricular tachycardia. Asymptomatic atrial fibrillation controlled on medication is allowed.
- •No cardiac conduction disturbances or medication potentially causing them:
- •QTc interval prolongation with other medications that required discontinuation of the treatment
- •Congenital long QT-syndrome or unexplained sudden death of first degree relative under 40 years of age
- •QTc interval > 480 msec (note: when this is the case on screening ECG, the ECG may be repeated twice. If the average QT-interval of these 3 measurements remains below 480 msec, patient is eligible)
- •Patients on medication potentially prolongating the QT-interval are excluded if the QT-interval is > 460 msec (Appendix, table 2).
- •Medication that might cause QT-prolongation or Torsades de pointes tachycardia is not allowed (Appendix, Table 1). Drugs with a risk of prolongating the QT-interval that cannot be discontinued are allowed, however, under close monitoring by the treating physician (Appendix, table 2).
- •No uncontrolled infectious disease
- •No other active malignancy
- •No major surgery (excluding diagnostic procedures like e.g., mediastinoscopy) in previous 4 weeks
- •No treatment with investigational drugs in 4 weeks prior to or during this study
- •No chronic systemic immune therapy
- •No known G6PD deficiency
排除标准
- •The opposite of the above
研究组 & 干预措施
Chloroquine
Patients receive Chloroquine
干预措施: Chloroquine, A-CQ 100 (Drug)
结局指标
主要结局
To determine the toxicity of adding chloroquine in escalating doses in SCLC patients: to standard dose cisplatin-etoposide in extensive disease SCLC; to standard dose concurrent radiotherapy and cisplatin-etoposide in limited disease SCLC
时间窗: 6 years
次要结局
- Tumor response (according to RECIST)(6 years)
- Overall survival(6 years)