Study on Systemic and Airway Cytokines and Oxidative Stress in Lung Cancer Patients Undergoing Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2012 by The University of Hong Kong
Sponsor:
Information provided by (Responsible Party):
James Chung-Man HO, The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT00956852
First received: August 9, 2009
Last updated: June 12, 2012
Last verified: June 2012
  Purpose

Lung cancer has remained as the top cancer killer in Hong Kong. Even for early resectable stage of lung cancer, only around 60-70% of patients can survive for 5 years after operation, mostly related to disease recurrence. Therefore there is urgent need for predictive biomarkers that can potentially help in monitoring patients for risk of disease recurrence after operation. Recent studies have suggested an important role of oxidative stress in the development of lung cancer and our preliminary data have suggested that some of the oxidative stress markers in blood could be predictive of response to systemic chemotherapy for lung cancer. Apart from potential biomarkers from blood, ongoing study has also been conducted to investigate the predictive role of biomarkers in exhaled breath condensate in lung cancer patients undergoing chemotherapy. Exhaled breath condensate can be collected simply with a disposable commercially available device that allows trapping of breath condensate via a cooling column during normal breathing for 20 minutes. Therefore this study aims at investigating the role of blood and exhaled breath condensate oxidative stress biomarkers before and after surgical lung resection for lung cancer in predicting subsequent clinical outcome, i.e., timing of disease recurrence. Recruited subjects will undergo interval sampling of blood and exhaled breath condensate, without any additional invasive interventions. The study subjects will be followed up for 5 years for subsequent disease recurrence.


Condition
Lung Cancer

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Study on Systemic and Airway Cytokines and Oxidative Stress in Patients With Non-small Cell Lung Cancer (NSCLC) Undergoing Surgical Lung Resections

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • Time to disease recurrence [ Time Frame: 24 months after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free survival [ Time Frame: 24 months after surgery ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples Without DNA

Plasma, buffy coat, red blood cell and exhaled breath condensate samples.


Estimated Enrollment: 100
Study Start Date: September 2008
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Lung cancer
Non-small cell lung cancer patients undergoing surgical lung resections

Detailed Description:

Lung cancer is the major cause of cancer deaths among both genders in Hong Kong. In 2005, primary lung cancer accounted for 33% and 25% of all cancer deaths in men and women respectively. On average, there are around 4,000 new cases of lung cancer each year. Non-small cell lung cancer (NSCLC) accounts for about 80% of all primary lung cancers. About 60% of cases present as advanced stages IIIB and IV disease. The currently available treatment modalities include surgery, radiotherapy and systemic chemotherapy. However, the overall prognosis remains dismal with 5-year survival rate less than 15%. Among those with early stage lung cancer, the 5-year survival rate is still suboptimal at around 60-70%. Therefore, there has been immense interest in the development of novel biomarkers to delineate the high risk group for subsequent tumour recurrence after curative lung resections. It has long been found that cellular prooxidant states promote cells to neoplastic growth, in part due to DNA damage caused by reactive oxygen species (ROS), i.e. superoxide anion and hydroxyl radical. The potential therapeutic role of antioxidants in the chemoprevention of lung cancer has therefore been brought to major clinical trials in recent years. Disappointingly, the major landmark chemoprevention trials including the Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) study and the Beta-Carotene and Retinol Efficacy Trial (CARET) have failed to demonstrate therapeutic benefits of vitamins A and E in lung cancer. Apart from the criticism about the dosages being used in the trials, these results may reflect the lack of understanding of the exact role of antioxidants in lung carcinogenesis. The simple use of general antioxidants, vitamins A and E, may not be able to target specifically the peculiar alterations in antioxidant profiles that lead to the development of lung cancer. In fact, our recent study has demonstrated specific changes in antioxidant expressions in surgically resected non-small cell lung cancer. In the resected lung cancer tissues, there were increased manganese superoxide dismutase (Mn SOD) and decreased catalase expressions at the transcriptional levels as compared with adjacent normal lung tissues. It has been hypothesized that this alteration in local antioxidant levels may result in anti-apoptosis and accumulation of genetic damages thus perpetuating carcinogenesis. However the exact clinical implications are still under investigation. Our previous case-control study on the systemic (erythrocyte) antioxidant activities in patients with NSCLC has shown an increased glutathione peroxidase (GPx), but decreased SOD activities compared with healthy controls. The erythrocyte SOD activity was associated with disease staging. In addition, our recent study on longitudinal profile of erythrocyte antioxidants during chemotherapy for advanced NSCLC has identified total glutathione as an independent predictor to treatment response, which may reflect tumour load (submitted, unpublished data).

Exhaled breath condensate (EBC) has recently emerged as a non-invasive sampling method for real-time analysis and evaluation of oxidative stress biomarkers in the lower respiratory tract airways, especially in various lung diseases including asthma, chronic obstructive pulmonary disease, and lung cancer. In particular, endothelin-1 and interleukin-6 have been found to be elevated in the EBC from patients with lung cancer. Therefore, the current study aims to evaluate the temporal changes of various oxidative stress biomarkers and cytokines in EBC and blood in patients with NSCLC who are undergoing surgical lung resections and the potential role of these parameters in predicting subsequent tumour recurrence. Also, the correlation of biomarkers in blood or EBC with lung tumour tissue will be looked into.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with early stage NSCLC who undergo curative lung resections in the Division of Cardiothoracic Surgery, Department of Surgery, Queen Mary Hospital will be recruited.

Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed early-stage non-small cell lung cancer undergoing curative surgical lung resections.
  • Life expectancy > 12 weeks.

Exclusion Criteria:

  • Respiratory failure requiring use of supplemental oxygen therapy.
  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: NCT00956852

Contacts
Contact: Chung-man James Ho 852-28554999 jhocm@hkucc.hku.hk

Locations
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Contact: Chung-man James Ho    852-28554999    jhocm@hkucc.hku.hk   
Principal Investigator: Chung-man James Ho, MD,FRCP         
Sub-Investigator: Alan Sihoe, MBBChir,FRCS         
Sub-Investigator: L C Cheng, MBBS,FRCS         
Sub-Investigator: Maria Wong, MD,FRCPath         
Sponsors and Collaborators
The University of Hong Kong
Investigators
Principal Investigator: Chung-man James Ho The University of Hong Kong
  More Information

No publications provided

Responsible Party: James Chung-Man HO, Clinical Assistant Professor, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT00956852     History of Changes
Other Study ID Numbers: UW 08-249
Study First Received: August 9, 2009
Last Updated: June 12, 2012
Health Authority: Hong Kong: Ethics Committee

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 22, 2014