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Metformin Plus TKI Use in Patients With Non-Small Cell Lung Carcinoma

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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
Sponsor:
Information provided by (Responsible Party):
Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico

Brief Summary:

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

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Other
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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Intervention
TKI plus Metformin
Drug: Metformin
500 mg PO BID
Other Name: DABEXR

Drug: TKI
standard dose
Other Names:
  • erlotinib
  • afatinib
  • gefitinib

Active Comparator: Control
TKI
Drug: TKI
standard dose
Other Names:
  • erlotinib
  • afatinib
  • gefitinib




Primary Outcome Measures :
  1. Overall Survival [ Time Frame: Start of treatment until 1-year follow-up ]

Secondary Outcome Measures :
  1. Response Rate [ Time Frame: 3 month evaluation after start of treatment ]
    Inflammatory markers (IL-6, IL-12, TNF-alpha)



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • NSCLC EGFR mutation-positive
  • Use of only Metformin as oral hypoglucemic agent
  • ECOG-PS 0-2
  • Measurable disease
  • Life expectancy >12 weeks

Exclusion Criteria:

  • Systemic disease
  • Patients with TKI treatment longer than 2 months
  • History of other neoplasm in the past 5 years
  • Breastfeeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03071705


Contacts
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Contact: Oscar Arrieta, MD, MSc 01 55 5628 0400 ext 71100 ogar@servidor.unam.mx

Locations
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Mexico
Instituto National de Cancerologia Recruiting
Mexico, Mexico, 14080
Contact: Oscar Gerardo MD Arrieta, Oncology    015556280400 ext 71101    ogar@servidor.unam.mx   
Sponsors and Collaborators
Instituto Nacional de Cancerologia de Mexico
Investigators
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Study Director: Oscar Arrieta, MD, MSc Instituto Nacional de Cancerología

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Oscar Gerardo Arrieta Rodríguez MD, Head Thoracic Oncology Unit, Instituto Nacional de Cancerologia de Mexico
ClinicalTrials.gov Identifier: NCT03071705     History of Changes
Other Study ID Numbers: 016/018/ICI
Ethics Committe ( Other Identifier: CEI/1019/16 )
First Posted: March 7, 2017    Key Record Dates
Last Update Posted: March 7, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data will be uploaded to a repository in an anonimized manner to preserve patient confidentiality.
Keywords provided by Oscar Gerardo Arrieta Rodríguez MD, Instituto Nacional de Cancerologia de Mexico:
NSCLC
metformin
metformin plus TKI
EGFR positive status
Additional relevant MeSH terms:
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Lung Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Bronchial Neoplasms
Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs