To determine the toxicity of adding chloroquine in escalating doses in SCLC patients - to standard dose cisplatin-etoposide in extensive disease SCLC = STEP 1 - to standard dose concurrent radiotherapy and cisplatin-etoposide in limited disease SCLC = STEP2 MedDRA version: 12.0 Level: PT Classification code 10041068 Term: Small cell lung cancer extensive stage MedDRA version: 12.0 Level: PT Classification code 10041069 Term: Small cell lung cancer limited stage
Conditions
Interventions
Trade Name: A-CQ 100
Product Name: Chloroquine
Product Code: A-CQ 100
Pharmaceutical Form: Tablet
Sponsors
MAASTRO Clinic
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Fase I, Step 1: chloroquine added to standard dose cisplatin-etoposide in extensive disease SCLC. 1. Histologically or cytologically confirmed ``extensive disease`` (Stage T0-4 N0-3 M1) small cell lung cancer 2. At least one measurable disease site, defined as lesion of = 1 cm unidimensionally on CT-scan. 3. WHO performance status 0-2 4. Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l. 5. Calculated creatinine clearance at least 60 ml/min 6. 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) 7. No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC. 8. Life expectancy more than 6 months 9. Willing and able to comply with the study prescriptions 10. 18 years or older 11. Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study 12. Ability to give and having given written informed consent before patient registration 13. No mixed pathology, e.g. non-small cell plus small cell cancer Fase I, Step 2: chloroquine added to standard dose cisplatin-etoposide plus radiotherapy in limited disease SCLC. 1. Histologically or cytologically confirmed `limited disease` ie stage T0-4 N0-3 M0 small cell lung cancer, excluding malignant pleural/pericardial effusion. 2. At least one measurable disease site, defined as lesion of = 1 cm unidimensionally on CT-scan. 3. WHO performance status 0-2 4. Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l. 5. Calculated creatinine clearance at least 60 ml/min 6. 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) 7. No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC. 8. Life expectancy more than 6 months 9. Willing and able to comply with the study prescriptions 10. 18 years or older 11. Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study 12. Ability to give and having given written informed consent before patient registration 13. No mixed pathology, e.g. non-small cell plus small cell cancer Fase II, step 1: 1. Histologically or cytologically confirmed ``extensive disease`` (Stage T0-4 N0-3 M1) small cell lung cancer 2. At least one measurable disease site, defined as lesion of = 1 cm unidimensionally on CT-scan 3. WHO performance status 0-2 4. Absolute neutrophil count at least 1800/µl and platelets at least 100000/µl and hemoglobin at least 6.2 mmol/l. 5. Calculated creatinine clearance at least 60 ml/min 6. 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) 7. No previous platinum chemotherapy or topo-isomerase-inhibitors for SCLC. 8. Life expectancy more than 6 months 9. Willing and able to comply with the study prescriptions 10. 18 years or older 11. Not pregnant or breast feeding and willing to take adequate contraceptive measures during the study 12. Ability to give and having given written informed consent before patient registra
Exclusion criteria
Exclusion criteria: the opposite of the above
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: fase I, step 1:To determine the toxicity of adding chloroquine in escalating doses in SCLC patients to standard dose cisplatin-etoposide in extensive disease SCLC fase I, step 2:To determine the toxicity of adding chloroquine in escalating doses in SCLC patients to standard dose concurrent radiotherapy and cisplatin-etoposide in limited disease SCLC fase II, step 1:To prove the efficacy of adding chloroquine to standard chemotherapy in a RPTD of … mg/day in extensive disease small cell lung cancer patients. fase II, step2:To prove the efficacy of adding chloroquine to standard chemotherapy and radiotherapy in a RPTD of … mg/day in limited disease small cell lung cancer patients. ;Secondary Objective: fase I, step 1 and fase I, step 2: - Tumor response (according to RECIST) - Overall survival fase II, step 1: 1. Complete and overall tumor response rates (according to RECIST) as judged on a CT Thorax at 2-3 weeks after the last day of administration of chemotherapy 2. Recording of the evolution of circulating biomarkers of hypoxia during therapy (hypothesis generating) 3. Toxicity (CTC AE 4.0) 4. Overall survival recorded at 1 year after the first day of chloroquine fase II, step 2: 1. Complete and overall tumor response rates (according to RECIST) as judged on a CT Thorax at 2-3 weeks after the last day of administration of chemotherapy 2. Recording of the evolution of circulating biomarkers of hypoxia during therapy (hypothesis generating) 3. Toxicity (CTC AE 4.0) ;Primary end point(s): Fase I, step 1 and 2: Toxicity (CTCAE 4.0) Fase II, step 1 : progression free survival Fase II, step 2: overall survival at 2 years | — |
Countries
Netherlands
Outcome results
None listed