{
"info": {
"nct_id": "NCT01575782",
"official_title": "Chloroquine as an Anti-autophagic Radiosensitizing Drug in Stage I-III Small Cell Lung Cancer (SCLC) Patients: a Phase I Trial.",
"inclusion_criteria": "* Histologically or cytologically confirmed stage I-III small cell lung cancer, excluding malignant pleural/pericardial effusion.\n* At least one measurable disease site, defined as lesion of ≥ 1 cm unidimensionally on CT-scan\n* WHO performance status 0-2\n* Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l.\n* Adequate renal function: calculated creatinine clearance at least 60 ml/min\n* 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)\n* No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC.\n* Lung function: FEV1 at least 30 % and DLCO at least 30 % of the age predicted value\n* No history of prior chest radiotherapy\n* Life expectancy more than 6 months\n* Willing and able to comply with the study prescriptions\n* 18 years or older\n* Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study\n* Ability to give and having given written informed consent before patient registration\n* No mixed pathology, e.g. non-small cell plus small cell cancer\n* No recent (< 3 months) severe cardiac disease (NYHA class >1) (congestive heart failure, infarction)\n* 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.\n* No cardiac conduction disturbances or medication potentially causing them:\n* QTc interval prolongation with other medications that required discontinuation of the treatment\n* Congenital long QT-syndrome or unexplained sudden death of first degree relative under 40 years of age\n* 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)\n* Patients on medication potentially prolongating the QT-interval are excluded if the QT-interval is > 460 msec (Appendix, table 2).\n* 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).\n* Complete left bundle branch block\n* No uncontrolled infectious disease\n* No other active malignancy\n* No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy) in previous 4 weeks\n* No treatment with investigational drugs in 4 weeks prior to or during this study\n* No chronic systemic immune therapy\n* No known G6PD deficiency\n* Patients must not have psoriasis or porphyria.\n* No known hypersensitivity to 4-aminoquinoline compound.\n* Patients must not have retinal or visual field changes from prior 4-aminoquinoline compound use.\n* No known prior hypersensitivity to cisplatin, etoposide or chloroquine or any of their components.\nHealthy volunteers allowed\nMust have minimum age of 18 Years",
"exclusion_criteria": "- The opposite of the above",
"miscellaneous_criteria": ""
},
"inclusion_lines": [
{
"line": "* Histologically or cytologically confirmed stage I-III small cell lung cancer, excluding malignant pleural/pericardial effusion.",
"criterions": [
{
"exact_snippets": "Histologically or cytologically confirmed",
"criterion": "confirmation method",
"requirements": [
{
"requirement_type": "method",
"expected_value": [
"histologically",
"cytologically"
]
}
]
},
{
"exact_snippets": "stage I-III small cell lung cancer",
"criterion": "cancer stage",
"requirements": [
{
"requirement_type": "stage",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 1,
"unit": "stage"
},
{
"operator": "<=",
"value": 3,
"unit": "stage"
}
]
}
}
]
},
{
"exact_snippets": "small cell lung cancer",
"criterion": "cancer type",
"requirements": [
{
"requirement_type": "type",
"expected_value": "small cell lung cancer"
}
]
},
{
"exact_snippets": "excluding malignant pleural/pericardial effusion",
"criterion": "malignant pleural/pericardial effusion",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* At least one measurable disease site, defined as lesion of ≥ 1 cm unidimensionally on CT-scan",
"criterions": [
{
"exact_snippets": "At least one measurable disease site, defined as lesion of ≥ 1 cm unidimensionally on CT-scan",
"criterion": "measurable disease site",
"requirements": [
{
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 1,
"unit": "site"
}
},
{
"requirement_type": "size",
"expected_value": {
"operator": ">=",
"value": 1,
"unit": "cm"
}
}
]
}
]
},
{
"line": "* WHO performance status 0-2",
"criterions": [
{
"exact_snippets": "WHO performance status 0-2",
"criterion": "WHO performance status",
"requirements": [
{
"requirement_type": "range",
"expected_value": {
"comparisons": [
{
"operator": ">=",
"value": 0,
"unit": "N/A"
},
{
"operator": "<=",
"value": 2,
"unit": "N/A"
}
]
}
}
]
}
]
},
{
"line": "* Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l.",
"criterions": [
{
"exact_snippets": "Absolute neutrophil count at least 1800/µl",
"criterion": "absolute neutrophil count",
"requirements": [
{
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 1800,
"unit": "µl"
}
}
]
},
{
"exact_snippets": "platelets at least 100000/µl",
"criterion": "platelets",
"requirements": [
{
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 100000,
"unit": "µl"
}
}
]
},
{
"exact_snippets": "hemoglobin at least 6.2 mmol/l",
"criterion": "hemoglobin",
"requirements": [
{
"requirement_type": "quantity",
"expected_value": {
"operator": ">=",
"value": 6.2,
"unit": "mmol/l"
}
}
]
}
]
},
{
"line": "* Adequate renal function: calculated creatinine clearance at least 60 ml/min",
"criterions": [
{
"exact_snippets": "Adequate renal function: calculated creatinine clearance at least 60 ml/min",
"criterion": "renal function",
"requirements": [
{
"requirement_type": "creatinine clearance",
"expected_value": {
"operator": ">=",
"value": 60,
"unit": "ml/min"
}
}
]
}
]
},
{
"line": "* 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)",
"criterions": [
{
"exact_snippets": "Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution",
"criterion": "total bilirubin",
"requirements": [
{
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 1.5,
"unit": "x ULN"
}
}
]
},
{
"exact_snippets": "ALT, AST, and alkaline phosphatase ≤ 2.5 x ULN for the institution",
"criterion": "ALT, AST, and alkaline phosphatase",
"requirements": [
{
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 2.5,
"unit": "x ULN"
}
}
]
},
{
"exact_snippets": "ALT, AST, and alkaline phosphatase ... (in case of liver metastases ≤ 5 x ULN for the institution)",
"criterion": "ALT, AST, and alkaline phosphatase in case of liver metastases",
"requirements": [
{
"requirement_type": "level",
"expected_value": {
"operator": "<=",
"value": 5,
"unit": "x ULN"
}
}
]
}
]
},
{
"line": "* No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC.",
"criterions": [
{
"exact_snippets": "No previous platinum chemotherapy",
"criterion": "previous platinum chemotherapy",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "No previous ... topo-isomerase-inhibitors for SCLC",
"criterion": "previous topo-isomerase-inhibitors for SCLC",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* Lung function: FEV1 at least 30 % and DLCO at least 30 % of the age predicted value",
"criterions": [
{
"exact_snippets": "Lung function: FEV1 at least 30 %",
"criterion": "FEV1",
"requirements": [
{
"requirement_type": "percentage of age predicted value",
"expected_value": {
"operator": ">=",
"value": 30,
"unit": "%"
}
}
]
},
{
"exact_snippets": "DLCO at least 30 % of the age predicted value",
"criterion": "DLCO",
"requirements": [
{
"requirement_type": "percentage of age predicted value",
"expected_value": {
"operator": ">=",
"value": 30,
"unit": "%"
}
}
]
}
]
},
{
"line": "* No history of prior chest radiotherapy",
"criterions": [
{
"exact_snippets": "No history of prior chest radiotherapy",
"criterion": "chest radiotherapy",
"requirements": [
{
"requirement_type": "history",
"expected_value": false
}
]
}
]
},
{
"line": "* Life expectancy more than 6 months",
"criterions": [
{
"exact_snippets": "Life expectancy more than 6 months",
"criterion": "life expectancy",
"requirements": [
{
"requirement_type": "duration",
"expected_value": {
"operator": ">",
"value": 6,
"unit": "months"
}
}
]
}
]
},
{
"line": "* Willing and able to comply with the study prescriptions",
"criterions": [
{
"exact_snippets": "Willing and able to comply with the study prescriptions",
"criterion": "compliance with study prescriptions",
"requirements": [
{
"requirement_type": "willingness",
"expected_value": true
},
{
"requirement_type": "ability",
"expected_value": true
}
]
}
]
},
{
"line": "* 18 years or older",
"criterions": [
{
"exact_snippets": "18 years or older",
"criterion": "age",
"requirements": [
{
"requirement_type": "minimum age",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "years"
}
}
]
}
]
},
{
"line": "* Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study",
"criterions": [
{
"exact_snippets": "Not pregnant",
"criterion": "pregnancy status",
"requirements": [
{
"requirement_type": "status",
"expected_value": false
}
]
},
{
"exact_snippets": "breast feeding",
"criterion": "breastfeeding status",
"requirements": [
{
"requirement_type": "status",
"expected_value": false
}
]
},
{
"exact_snippets": "willing to take adequate contraceptive measures",
"criterion": "contraceptive measures",
"requirements": [
{
"requirement_type": "willingness",
"expected_value": true
}
]
}
]
},
{
"line": "* Ability to give and having given written informed consent before patient registration",
"criterions": [
{
"exact_snippets": "Ability to give and having given written informed consent",
"criterion": "written informed consent",
"requirements": [
{
"requirement_type": "ability",
"expected_value": true
},
{
"requirement_type": "status",
"expected_value": "given"
}
]
}
]
},
{
"line": "* No mixed pathology, e.g. non-small cell plus small cell cancer",
"criterions": [
{
"exact_snippets": "No mixed pathology, e.g. non-small cell plus small cell cancer",
"criterion": "mixed pathology",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* No recent (< 3 months) severe cardiac disease (NYHA class >1) (congestive heart failure, infarction)",
"criterions": [
{
"exact_snippets": "recent (< 3 months) severe cardiac disease",
"criterion": "recent severe cardiac disease",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "NYHA class >1",
"criterion": "NYHA class",
"requirements": [
{
"requirement_type": "severity",
"expected_value": {
"operator": ">",
"value": 1,
"unit": "N/A"
}
}
]
},
{
"exact_snippets": "congestive heart failure",
"criterion": "congestive heart failure",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "infarction",
"criterion": "infarction",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* 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.",
"criterions": [
{
"exact_snippets": "No history of cardiac arrythmia",
"criterion": "cardiac arrhythmia history",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "multifocal premature ventricular contractions",
"criterion": "multifocal premature ventricular contractions",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "uncontrolled atrial fibrillation",
"criterion": "uncontrolled atrial fibrillation",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "bigeminy",
"criterion": "bigeminy",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "trigeminy",
"criterion": "trigeminy",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "ventricular tachycardia",
"criterion": "ventricular tachycardia",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "symptomatic and requiring treatment (CTC AE 3.0)",
"criterion": "symptomatic cardiac arrhythmia requiring treatment",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "asymptomatic sustained ventricular tachycardia",
"criterion": "asymptomatic sustained ventricular tachycardia",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "Asymptomatic atrial fibrillation controlled on medication is allowed",
"criterion": "asymptomatic atrial fibrillation controlled on medication",
"requirements": [
{
"requirement_type": "presence",
"expected_value": true
}
]
}
]
},
{
"line": "* No cardiac conduction disturbances or medication potentially causing them:",
"criterions": [
{
"exact_snippets": "No cardiac conduction disturbances",
"criterion": "cardiac conduction disturbances",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "No ... medication potentially causing them",
"criterion": "medication potentially causing cardiac conduction disturbances",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* QTc interval prolongation with other medications that required discontinuation of the treatment",
"criterions": [
{
"exact_snippets": "QTc interval prolongation",
"criterion": "QTc interval",
"requirements": [
{
"requirement_type": "prolongation",
"expected_value": true
}
]
},
{
"exact_snippets": "with other medications that required discontinuation of the treatment",
"criterion": "medication history",
"requirements": [
{
"requirement_type": "discontinuation due to QTc prolongation",
"expected_value": true
}
]
}
]
},
{
"line": "* Congenital long QT-syndrome or unexplained sudden death of first degree relative under 40 years of age",
"criterions": [
{
"exact_snippets": "Congenital long QT-syndrome",
"criterion": "congenital long QT-syndrome",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "unexplained sudden death of first degree relative under 40 years of age",
"criterion": "unexplained sudden death of first degree relative",
"requirements": [
{
"requirement_type": "age",
"expected_value": {
"operator": "<",
"value": 40,
"unit": "years"
}
}
]
}
]
},
{
"line": "* 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)",
"criterions": [
{
"exact_snippets": "QT interval > 480 msec ... average QT-interval of these 3 measurements remains below 480 msec",
"criterion": "QT interval",
"requirements": [
{
"requirement_type": "duration",
"expected_value": {
"operator": ">",
"value": 480,
"unit": "msec"
}
},
{
"requirement_type": "average duration",
"expected_value": {
"operator": "<",
"value": 480,
"unit": "msec"
}
}
]
}
]
},
{
"line": "* Patients on medication potentially prolongating the QT-interval are excluded if the QT-interval is > 460 msec (Appendix, table 2).",
"criterions": [
{
"exact_snippets": "Patients on medication potentially prolongating the QT-interval",
"criterion": "medication",
"requirements": [
{
"requirement_type": "effect",
"expected_value": "potentially prolongating the QT-interval"
}
]
},
{
"exact_snippets": "QT-interval is > 460 msec",
"criterion": "QT-interval",
"requirements": [
{
"requirement_type": "duration",
"expected_value": {
"operator": ">",
"value": 460,
"unit": "msec"
}
}
]
}
]
},
{
"line": "* 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).",
"criterions": [
{
"exact_snippets": "Medication that might cause QT-prolongation or Torsades de pointes tachycardia is not allowed",
"criterion": "medication causing QT-prolongation or Torsades de pointes tachycardia",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "Drugs with a risk of prolongating the QT-interval that cannot be discontinued are allowed, however, under close monitoring by the treating physician",
"criterion": "drugs with a risk of prolongating the QT-interval",
"requirements": [
{
"requirement_type": "discontinuation",
"expected_value": false
},
{
"requirement_type": "monitoring",
"expected_value": "close monitoring by the treating physician"
}
]
}
]
},
{
"line": "* Complete left bundle branch block",
"criterions": [
{
"exact_snippets": "Complete left bundle branch block",
"criterion": "left bundle branch block",
"requirements": [
{
"requirement_type": "completeness",
"expected_value": "complete"
}
]
}
]
},
{
"line": "* No uncontrolled infectious disease",
"criterions": [
{
"exact_snippets": "uncontrolled infectious disease",
"criterion": "infectious disease",
"requirements": [
{
"requirement_type": "control",
"expected_value": true
}
]
}
]
},
{
"line": "* No other active malignancy",
"criterions": [
{
"exact_snippets": "No other active malignancy",
"criterion": "active malignancy",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* No major surgery (excluding diagnostic procedures like e.g. mediastinoscopy) in previous 4 weeks",
"criterions": [
{
"exact_snippets": "No major surgery ... in previous 4 weeks",
"criterion": "major surgery",
"requirements": [
{
"requirement_type": "time since last occurrence",
"expected_value": {
"operator": ">=",
"value": 4,
"unit": "weeks"
}
}
]
}
]
},
{
"line": "* No treatment with investigational drugs in 4 weeks prior to or during this study",
"criterions": [
{
"exact_snippets": "No treatment with investigational drugs in 4 weeks prior to or during this study",
"criterion": "treatment with investigational drugs",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
},
{
"requirement_type": "time frame",
"expected_value": "4 weeks prior to or during this study"
}
]
}
]
},
{
"line": "* No chronic systemic immune therapy",
"criterions": [
{
"exact_snippets": "No chronic systemic immune therapy",
"criterion": "chronic systemic immune therapy",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* No known G6PD deficiency",
"criterions": [
{
"exact_snippets": "No known G6PD deficiency",
"criterion": "G6PD deficiency",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* Patients must not have psoriasis or porphyria.",
"criterions": [
{
"exact_snippets": "must not have psoriasis",
"criterion": "psoriasis",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "must not have ... porphyria",
"criterion": "porphyria",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* No known hypersensitivity to 4-aminoquinoline compound.",
"criterions": [
{
"exact_snippets": "No known hypersensitivity to 4-aminoquinoline compound.",
"criterion": "hypersensitivity to 4-aminoquinoline compound",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "* Patients must not have retinal or visual field changes from prior 4-aminoquinoline compound use.",
"criterions": [
{
"exact_snippets": "retinal or visual field changes from prior 4-aminoquinoline compound use",
"criterion": "retinal or visual field changes",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
},
{
"line": "Healthy volunteers allowed",
"criterions": [
{
"exact_snippets": "Healthy volunteers allowed",
"criterion": "volunteer health status",
"requirements": [
{
"requirement_type": "status",
"expected_value": "healthy"
}
]
}
]
},
{
"line": "Must have minimum age of 18 Years",
"criterions": [
{
"exact_snippets": "minimum age of 18 Years",
"criterion": "age",
"requirements": [
{
"requirement_type": "minimum",
"expected_value": {
"operator": ">=",
"value": 18,
"unit": "Years"
}
}
]
}
]
}
],
"exclusion_lines": [
{
"line": "- The opposite of the above",
"criterions": [
{
"exact_snippets": "The opposite of the above",
"criterion": "opposite condition",
"requirements": [
{
"requirement_type": "N/A",
"expected_value": "opposite of previous criteria"
}
]
}
]
}
],
"miscellaneous_lines": [],
"failed_inclusion": [
{
"line": "* No known prior hypersensitivity to cisplatin, etoposide or chloroquine or any of their components.",
"criterions": [
{
"exact_snippets": "No known prior hypersensitivity to cisplatin",
"criterion": "hypersensitivity to cisplatin",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "No known prior hypersensitivity to etoposide",
"criterion": "hypersensitivity to etoposide",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "No known prior hypersensitivity to chloroquine",
"criterion": "hypersensitivity to chloroquine",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
},
{
"exact_snippets": "No known prior hypersensitivity to ... any of their components",
"criterion": "hypersensitivity to components of cisplatin, etoposide, or chloroquine",
"requirements": [
{
"requirement_type": "presence",
"expected_value": false
}
]
}
]
}
],
"failed_exclusion": [],
"failed_miscellaneous": []
}