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

Maastricht Radiation Oncology

Status and phase

Terminated

Phase 1

Conditions

Small Cell Lung Cancer

Treatments

Drug: Chloroquine

Study type

Interventional

Funder types

Other

Identifiers

NCT01575782

CHLOROQUINE I-III

Details and patient eligibility

About

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.

Enrollment

5 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.