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Chloroquine as an Anti-Autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients (Chloroquine IV)

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ClinicalTrials.gov Identifier: NCT00969306
Recruitment Status : Completed
First Posted : September 1, 2009
Last Update Posted : April 14, 2017
Sponsor:
Collaborators:
Maastricht University Medical Center
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Maastricht Radiation Oncology

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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Drug: Chloroquine, A-CQ 100 Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Chloroquine as an Anti-autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients: A Phase 1 Trial
Actual Study Start Date : September 2013
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Chloroquine
Patients receive Chloroquine
Drug: Chloroquine, A-CQ 100

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 Measures :
  1. 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 Measures :
  1. Tumor response (according to RECIST) [ Time Frame: 6 years ]
  2. Overall survival [ Time Frame: 6 years ]


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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00969306


Locations
Netherlands
NKI/AvL
Amsterdam, Netherlands
VU Medical Center
Amsterdam, Netherlands
Maastricht Radiation Oncology
Maastricht, Netherlands
Maastricht University Medical Center
Maastricht, Netherlands
Sponsors and Collaborators
Maastricht Radiation Oncology
Maastricht University Medical Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Philippe Lambin, DM, PhD Maastricht Radiation Oncology

Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00969306     History of Changes
Other Study ID Numbers: Chloroquine IV
First Posted: September 1, 2009    Key Record Dates
Last Update Posted: April 14, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Chloroquine
Chloroquine diphosphate
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics