Clinical trial NCT02109549: 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.
Official title: Influence of Metformin Use on Treatment Outcome in NSCLC Patients
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non Small Cell Lung Cancer
Lead sponsor: Maastricht Radiation Oncology
Sponsor class: OTHER
Collaborators: name: Maastro Clinic, The Netherlands
name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
First posted: 2014-04-10
Enrollment: 70
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with advanced stage non-small cell lung cancer

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of metformin use
timeFrame: 2 years after radiotherapy
measure: Assessment of insulin use
timeFrame: 2 years after radiotherapy
Secondary outcomes:
measure: Overall assessment of overall survival and toxicity factors
timeFrame: 2 years after radiotherapy
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute (NKI)
city: Amsterdam
country: Netherlands
facility: AMC
city: Maastricht
country: Netherlands
facility: MAASTRO clinic
Study officials:
affiliation: Maastro Clinic, The Netherlands
name: Philippe Lambin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Maastro Clinic, The Netherlands
name: Esther Troost
role: STUDY_CHAIR
affiliation: NKI Amsterdam
name: José Belderbos
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Edith Dieleman
role: PRINCIPAL_INVESTIGATOR
References: