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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Maastricht Radiation Oncology
Sponsor:
Collaborators:
Maastricht University Medical Center
Information provided by (Responsible Party):
Maastricht Radiation Oncology
ClinicalTrials.gov Identifier:
NCT00969306
First received: August 31, 2009
Last updated: July 16, 2014
Last verified: March 2014
  Purpose

Chloroquine might very well be able to increase overall survival in small cell lung cancer by sensitizing cells resistant to chemotherapy and radiotherapy.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Maastricht Radiation Oncology:

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 [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response (according to RECIST) [ Time Frame: 6 years ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 6 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 208
Study Start Date: September 2013
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00969306

Contacts
Contact: Bart Reymen +31 88 44 55 666 bart.reymen@maastro.nl

Locations
Netherlands
VU Medical Center Not yet recruiting
Amsterdam, Netherlands
NKI/AvL Not yet recruiting
Amsterdam, Netherlands
Maastricht Radiation Oncology Recruiting
Maastricht, Netherlands
Contact: Bart Reymen    +31 88 4455666    bart.reymen@maastro.nl   
Sub-Investigator: Dirk De Ruysscher, MD, PhD         
Maastricht University Medical Center Not yet recruiting
Maastricht, Netherlands
Contact: Annemarie Dingemans, MD    +31 387 65 43      
Sub-Investigator: Annemarie Dingemans, MD         
Sponsors and Collaborators
Maastricht Radiation Oncology
Maastricht University Medical Center
Investigators
Principal Investigator: Philippe Lambin, DM, PhD Maastricht Radiation Oncology
  More Information

No publications provided

Responsible Party: Maastricht Radiation Oncology
ClinicalTrials.gov Identifier: NCT00969306     History of Changes
Other Study ID Numbers: Chloroquine IV
Study First Received: August 31, 2009
Last Updated: July 16, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

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
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on July 26, 2014