Influence of the Use of the Diabetic Drug Metformin on the Overall Survival and Treatment-related Toxicity in Advanced Stage Non-small Cell Lung Cancer Patients.

Non Small Cell Lung Cancer Clinical Trial

— Metformin  

Official title:

Influence of Metformin Use on Treatment Outcome in NSCLC Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02109549
• Other study ID #: Metformin NSCLC
• Status: Completed
• Phase: N/A
• First received: March 26, 2014
• Last updated: May 31, 2016
• Start date: March 2014
• Est. completion date: February 2016

Study information

• Verified date: May 2016
• Source: Maastricht Radiation Oncology
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial Summary

There are preliminary data suggesting that patients suffering from non-insulin-dependent diabetes mellitus, treated with metformin, have improved local tumor control. A reduction in the tumor's hypoxia may be responsible for this phenomenon.

Therefore, the aim of this study is to test the hypothesis in three cohorts of patients suffering from advanced stage non-small cell lung cancer and all undergoing concurrent radiochemotherapy: 1. Patients with diabetes mellitus treated with metformin only; 2. Patients with insulin-dependent diabetes mellitus not treated with metformin; 3. The remaining patients serving as controls. Furthermore, tumor and treatment-related parameters will be correlated with overall survival and morbidity.

Description:

There are preliminary clinical and preclinical data suggesting that patients suffering from non-insulin-dependent diabetes mellitus, treated with metformin, have improved local tumor control. The reduction in oxygen consumption of tumor cells and thus a relative reduction in the tumor's hypoxia may be responsible for this.

Non-small cell lung cancer is the most frequent solid tumor in many Western countries and the number one cause of cancer-related death. Even though the introduction of concurrent chemoradiotherapy has improved local tumor control and thus overall survival, 5-year overall survival is still as low as 14%. Furthermore, many patients are not eligible to undergo concurrent treatment thus reducing their chances to defeat this disease. Additionally, concurrent chemoradiotherapy is associated with increased toxicity compared to sequential treatment. Therefore, alternative additives improving the effect of radiotherapy without increasing toxicity to an unbearable level are searched for. One possible pharmaceutical is metformin; many patients have been using it in the past without evident increased toxicity, it is cheap, and widely available.

Thus, the aim of this study is to test the hypothesis that metformin increases overall survival without enhancing treatment-related toxicity. For this means, in three cohorts of patients suffering from advanced stage non-small cell lung cancer and all undergoing concurrent radiochemotherapy: 1. Patients with diabetes mellitus treated with metformin only; 2. Patients with insulin-dependent diabetes mellitus not treated with metformin; 3. The remaining patients serving as controls. Using Kaplan-Meier statistics as well as uni- and multivariate analysis, the overall survival and toxicity of these cohorts will be compared. Other potentially confounding factors will be tested as secondary endpoints.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

Advanced non-small cell lung cancer patients undergoing primary concurrent radiochemotherapy; patients treated with metformin or insulin will be analyzed as separate cohorts.

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non Small Cell Lung Cancer

Locations

Country	Name	City	State
Netherlands	AMC	Amsterdam
Netherlands	The Netherlands Cancer Institute (NKI)	Amsterdam
Netherlands	MAASTRO clinic	Maastricht

Sponsors (3)

Lead Sponsor	Collaborator
Maastricht Radiation Oncology	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Maastro Clinic, The Netherlands

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of metformin use	Assessment of metformin use (in patients with diabetes mellitus) on overall survival in advanced stage NSCLC patients undergoing radiochemotherapy.	2 years after radiotherapy	No
Primary	Assessment of insulin use	Assessment of insulin use (in patients with diabetes mellitus) on overall survival in advanced stage NSCLC patients undergoing radiochemotherapy.	2 years after radiotherapy	No
Secondary	Overall assessment of overall survival and toxicity factors	Composite outcome measure: Assessment of factors influencing overall survival and toxicity: Age Gender Performance status WHO TNM stage Histology Delivered radiation dose Total gross tumor volume Total planning target volume	2 years after radiotherapy	No