Metformin Plus TKI Use in Patients With Non-Small Cell Lung Carcinoma
|ClinicalTrials.gov Identifier: NCT03071705|
Recruitment Status : Unknown
Verified March 2017 by Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico.
Recruitment status was: Recruiting
First Posted : March 7, 2017
Last Update Posted : March 7, 2017
Treatment for patients with mutation in the epidermal growth factor receptor (EGFR) with specific domain tyrosine kinase inhibitors (TKIs) has given place to objective clinical response, increase in progression-free survival (PFS) compared to cytotoxic chemotherapy. However, despite clinical success with different TKIs, most patients eventually develop acquired resistance to these agents after an average period of time of 10 months.
Recently metformin, an oral hypoglycemic agent, has been associated with reduction in the global risk of incidence and mortality of different types of cancer, by exercising anti-tumor properties. Its role as a chemo-preventive and adjuvant drug in overcoming acquired resistance to chemotherapy, target therapy and immunotherapy in NSCLC is still under discussion.
However, preclinical data support the role as an adjuvant drug in the treatment of NSCLC in combination with chemotherapy or EGFR-TKIs. This evidence led to examine the effects of metformin in combination with EGFR-TKIs in a NSCLC cellular line panel, obtaining a different sensibility to the unique use with EGFR-TKIs. The combination of metformin and TKIs reduced the colony forming capacity and proliferation, and induced a huge pro-apoptotic effect in NSCLC cellular lines and resistance in EGFR-TKIs. This suggests that metformin may reduce the resistance to TKIs. A retrospective study in patients from our institution from 2008 to 2014, showed significant clinical benefit in patients who used metformin, improving the global survival. Based on these considerations, we propose a phase II randomized study to assess the effect and safety of metformin in combination with TKIs as second line therapy in patients with NSCLC in advanced stages with EGFR mutation.
The main objective of this study is to assess the progression-free survival period in patients with advanced non-small cell lung cancer in treatment with TKIs and metformin versus TKI alone.
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Adenocarcinoma Tyrosine Kinase Mutation EGFR Gene Mutation||Drug: Metformin Drug: TKI||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Effect of Metformin in Combination With Tyrosine Kinase Inhibitors (TKI) on Clinical, Biochemical and Nutritional in Patients With Non-Small Cell Lung Carcinoma (NSCLC): Randomized Clinical Trial|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||April 2017|
|Estimated Study Completion Date :||December 2017|
TKI plus Metformin
500 mg PO BID
Other Name: DABEXR
Active Comparator: Control
- Overall Survival [ Time Frame: Start of treatment until 1-year follow-up ]
- Response Rate [ Time Frame: 3 month evaluation after start of treatment ]Inflammatory markers (IL-6, IL-12, TNF-alpha)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071705
|Contact: Oscar Arrieta, MD, MSc||01 55 5628 0400 ext email@example.com|
|Instituto National de Cancerologia||Recruiting|
|Mexico, Mexico, 14080|
|Contact: Oscar Gerardo MD Arrieta, Oncology 015556280400 ext 71101 firstname.lastname@example.org|
|Study Director:||Oscar Arrieta, MD, MSc||Instituto Nacional de Cancerología|