Chloroquine as an Anti-Autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients
Information source: Maastricht Radiation Oncology
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Small Cell Lung Cancer
Intervention: Chloroquine, A-CQ 100 (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Maastricht Radiation Oncology Official(s) and/or principal investigator(s):
Philippe Lambin, DM, PhD, Principal Investigator, Affiliation: Maastricht Radiation Oncology
Overall contact:
Bart Reymen, Phone: +31 88 44 55 666, Email: bart.reymen@maastro.nl
Summary
Chloroquine might very well be able to increase overall survival in small cell lung cancer
by sensitizing cells resistant to chemotherapy and radiotherapy.
Clinical Details
Official title: Chloroquine as an Anti-autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients: A Phase 1 Trial
Study design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: 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: Tumor response (according to RECIST)Overall survival
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Bart Reymen, Phone: +31 88 44 55 666, Email: bart.reymen@maastro.nl
NKI/AvL, Amsterdam, Netherlands; Not yet recruiting
VU Medical Center, Amsterdam, Netherlands; Not yet recruiting
Maastricht Radiation Oncology, Maastricht, Netherlands; Recruiting
Bart Reymen, Phone: +31 88 4455666, Email: bart.reymen@maastro.nl
Dirk De Ruysscher, MD, PhD, Sub-Investigator
Maastricht University Medical Center, Maastricht, Netherlands; Not yet recruiting
Annemarie Dingemans, MD, Phone: +31 387 65 43
Annemarie Dingemans, MD, Sub-Investigator
Additional Information
Starting date: September 2013
Last updated: February 23, 2015
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