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

Chloroquine as an Anti-autophagy Drug in Stage IV Small Cell Lung Cancer (SCLC) Patients: A Phase 1 Trial

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

Study Overview

• Status: Terminated
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Chloroquine, A-CQ 100

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
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VU Medical Center
  • Amsterdam, Netherlands
    • NKI/AvL
  • Maastricht, Netherlands
    • Maastricht University Medical Center
  • Maastricht, Netherlands
    • Maastricht Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	6 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Tumor response (according to RECIST)	6 years
Overall survival	6 years

Collaborators and Investigators

• Sponsor: Maastricht Radiation Oncology
• Collaborators: National Cancer Institute (NCI); Maastricht University Medical Center
• Investigators: Principal Investigator: Philippe Lambin, DM, PhD, Maastricht Radiation Oncology

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: August 31, 2009
• First Submitted That Met QC Criteria: August 31, 2009
• First Posted (Estimate): September 1, 2009

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Anti-Infective Agents; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Chloroquine
• Other Study ID Numbers: Chloroquine IV