Chloroquine as an Anti-autophagic Radiosensitizing Drug in Stage I-III Small Cell Lung Cancer

Study Overview
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Brief Summary
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Chloroquine can make tumor cells less resistant to chemo/radiotherapy. In this trial chloroquine is given during radiotherapy. The dose is increased in cohorts of at least 3 patients.

Official Title
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Chloroquine as an Anti-autophagic Radiosensitizing Drug in Stage I-III Small Cell Lung Cancer (SCLC) Patients: a Phase I Trial.

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Chloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed stage I-III small cell lung cancer, excluding malignant pleural/pericardial effusion. 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. Adequate renal function: 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. Lung function: FEV1 at least 30 % and DLCO at least 30 % of the age predicted value No history of prior chest radiotherapy 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 3.0), 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 QT 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). Complete left bundle branch block 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 Patients must not have psoriasis or porphyria. No known hypersensitivity to 4-aminoquinoline compound. Patients must not have retinal or visual field changes from prior 4-aminoquinoline compound use. No known prior hypersensitivity to cisplatin, etoposide or chloroquine or any of their components. Exclusion Criteria: - The opposite of the above

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chloroquine<br> | Drug: Chloroquine<br>* Daily intake of Chloroquine during radiotherapy<br>* Other names: A-CQ 100mg per tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability |  | 3 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response of the tumour (regression, progression, stable disease) |  | 2 years after inclusion | 
| Overall survival |  | 2 years after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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small cell lung cancer, stage I-III, chloroquine, Phase I