Chloroquine as an Anti-Autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients (Chloroquine IV)
Primary Purpose
Small Cell Lung Cancer
Status
Terminated
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Chloroquine, A-CQ 100
Sponsored by
About this trial
This is an interventional treatment trial for Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- The opposite of the above
Sites / Locations
- NKI/AvL
- VU Medical Center
- Maastricht Radiation Oncology
- Maastricht University Medical Center
Arms of the Study
Arm 1
Arm Type
Active Comparator
Arm Label
Chloroquine
Arm Description
Patients receive Chloroquine
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Tumor response (according to RECIST)
Overall survival
Full Information
NCT ID
NCT00969306
First Posted
August 31, 2009
Last Updated
February 12, 2019
Sponsor
Maastricht Radiation Oncology
Collaborators
Maastricht University Medical Center, National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00969306
Brief Title
Chloroquine as an Anti-Autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients
Acronym
Chloroquine IV
Official Title
Chloroquine as an Anti-autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients: A Phase 1 Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
Poor accrual
Study Start Date
September 2013 (Actual)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht Radiation Oncology
Collaborators
Maastricht University Medical Center, National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
Chloroquine might very well be able to increase overall survival in small cell lung cancer by sensitizing cells resistant to chemotherapy and radiotherapy.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chloroquine
Arm Type
Active Comparator
Arm Description
Patients receive Chloroquine
Intervention Type
Drug
Intervention Name(s)
Chloroquine, A-CQ 100
Intervention Description
Administration:
Orally
Timing: Once daily
Tablets of 100 mg
During or after meals
In case of missed dose: intake of the missed dose is still possible up until 12 hours before the next dose.
Patients should always note date and time of intake on the chloroquine monitoring form.
Primary Outcome Measure Information:
Title
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
Time Frame
6 years
Secondary Outcome Measure Information:
Title
Tumor response (according to RECIST)
Time Frame
6 years
Title
Overall survival
Time Frame
6 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
The opposite of the above
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe Lambin, DM, PhD
Organizational Affiliation
Maastricht Radiation Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
NKI/AvL
City
Amsterdam
Country
Netherlands
Facility Name
VU Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Maastricht Radiation Oncology
City
Maastricht
Country
Netherlands
Facility Name
Maastricht University Medical Center
City
Maastricht
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Chloroquine as an Anti-Autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients
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