Metformin in Stage IV Lung Adenocarcinoma | RxWiki

Metformin in Stage IV Lung Adenocarcinoma

Overview[ - collapse ][ - ]

Purpose	The purpose of this study is to determine whether metformin is effective in lowering plasma IL-6 level and improving the treatment response in patients with non-small cell lung cancer
Condition	Non-small Cell Lung Cancer
Intervention	Drug: METFORMIN
Phase	Phase 2
Sponsor	National Cheng-Kung University Hospital
Responsible Party	National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier	NCT01997775
First Received	November 17, 2013
Last Updated	November 24, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	November 17, 2013
Last Updated Date	November 24, 2013
Start Date	August 2013
Estimated Primary Completion Date	December 2015
Current Primary Outcome Measures	The change of plasma IL-6 level after the treatment with metformin [Time Frame: 12 weeks] [Designated as safety issue: No]
Current Secondary Outcome Measures	The objective response rate (RR) [Time Frame: 2 YEARS] [Designated as safety issue: No] The progression free survival [Time Frame: 2 years] [Designated as safety issue: No] The overall survival [Time Frame: 2-years] [Designated as safety issue: No] Number of participants with adverse events [Time Frame: 2-years] [Designated as safety issue: Yes]All adverse events (AEs) occurring after the patient receiving the first dose of study drug will be monitored and recorded. Periodic measurement of vital signs, regular laboratory evaluation for hematology and blood chemistry will be arranged and these will be graded by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grades. Changes of quality of life [Time Frame: 2-years] [Designated as safety issue: No]The quality of life will be evaluated by the EQ-5D-3L questionnaire which will be completed at baseline, during the therapy, and post-therapy period

Descriptive Information[ + expand ][ + ]

Brief Title	Metformin in Stage IV Lung Adenocarcinoma
Official Title	A Phase II Trial to Examine the Effect of Metformin on Plasma IL-6 Level in Patients With Advanced Non-Small Cell Lung Cancer
Brief Summary	The purpose of this study is to determine whether metformin is effective in lowering plasma IL-6 level and improving the treatment response in patients with non-small cell lung cancer
Detailed Description	Interleukin-6 (IL-6) plays an important role in the pathogenesis of lung cancer. Several clinical studies show metformin could decrease IL-6 level in addition to the glucose-lowering effect. Preclinical data also reveal metformin could decrease the IL-6 production in lung cancer cells and enhance cytotoxicity of chemotherapy in animal model. Based on these findings, the purpose of this study is to determine whether metformin is effective in lowering plasma IL-6 level and improving the treatment response in patients with non-small cell lung cancer clinically. Patients with stage IV lung adenocarcinoma will be enrolled in this study and receive standard treatments for lung cancer, either chemotherapy combining cisplatin and pemetrexed or targeted therapy (Gefitinib). For patients with plasma IL-6 more than 2.0 pg/ml after 2 cycles of standard treatment, metformin will be given and titrated to 1500mg/day gradually. Plasma IL-6 level will be checked after use of metformin for 12 weeks. Tumor response to the standard treatment plus metformin will be evaluated and side effects of metformin will also be monitored.
Study Type	Interventional
Study Phase	Phase 2
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label
Condition	Non-small Cell Lung Cancer
Intervention	Drug: METFORMIN Participants enrolled in this study will be treated with either chemotherapy (Cisplatin 75mg/m2 plus Pemetrexed 500mg/m2 on D1) for 4 cycles or targeted therapy (Gefitinib 250mg/d) till disease progression according to physicians' decision. For participants with plasma IL-6 > 2.0 pg/mL after 2 cycles of chemotherapy or targeted therapy, Metformin 500mg orally qd will be given on Day 1 of cycle 3. If patient could tolerate it well, metformin will be titrated to 500mg bid in the following week (Cycle 3 D8) and 500mg tid in the 3rd week (Cycle 3 D15). For patients receiving chemotherapy, metformin will be used for total 12 weeks and plasma IL-6 level will be checked at the end of metformin treatment. For patients receiving targeted therapy, metformin will be used till disease progression and plasma IL-6 level will be measured after use of metformin for 12 weeks. Other Names: GLUCOPHAGE
Study Arm (s)	Experimental: METFORMIN For patients with stage IV lung adenocarcinoma and IL-6 level higher than 2.0 pg/ml after 2 cycles of standard treatment, metformin 500mg tid orally will be given.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	48
Estimated Completion Date	December 2015
Estimated Primary Completion Date	November 2015
Eligibility Criteria	Inclusion Criteria: 1. Histologically or cytologically confirmed lung adenocarcinoma. 2. Stage IV disease as defined by AJCC 7th edition staging. 3. At least one measurable lesion (as defined by RECIST v1.1). 4. No prior radiotherapy, chemotherapy, surgery, target therapy, or immunotherapy for NSCLC. (Except the surgery for biopsy or port-A implantation, palliative localized radiotherapy for bone metastasis). 5. Age ≤ 80 years old and ≥ 20 years old. 6. ECOG performance status of 0-2. 7. Adequate organ function, including followings Bone marrow: Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L; WBC ≥ 3.0 x 10^9/L Platelet count ≥ 100 x 10^9/L Hemoglobin ≥ 9g/dL Hepatic: Total bilirubin level ≤ 1.0 x UNL AST and ALT ≤ 3.0 x UNL; Renal: Creatinine level ≤ 1.5 mg/dL in men, ≤1.4 mg/dL in women; or Estimated CCr ≥ 60 mL/min. (CCr is estimated by Cockcroft-Gault formula, as appendix II)(CCr is estimated by Cockcroft-Gault formula) 8. Estimated life expectancy of at least 6 months. 9. Written (signed) Informed Consent. Exclusion Criteria: 1. With other primary malignancies, except those remain disease-free for 3 or more years after curative treatment, basal cell cancer of the skin or in situ cervical cancer. 2. Use of other anti-cancer therapy, including chemotherapy, target therapy, immunotherapy, radiotherapy, and hormone therapy. 3. Prior participation in any investigational drug study within 28 days. 4. Use of anti-IL-6 or IL-6-lowering agents. 5. Use of metformin in the past 6 months. 6. Poor controlled diabetes (HbA1c ≥ 8.0%). 7. Known hypersensitivity or intolerance to metformin. 8. Congestive heart failure with NYHA functional class II~IV. 9. History of lactic acidosis. 10. Significant concurrent medical diseases, such as unstable angina, acute or recent myocardial infarction (< 6 months before enrollment), COPD with frequent exacerbation, uncontrolled hypertension, or recent CVA (< 6 months before enrollment). 11. Active uncontrolled infections or HIV infection. 12. Psychiatric disorders that would compromise the patient's compliance or decision. 13. Current or planned pregnancy, or breast feeding in women. 14. Poor compliance.
Gender	Both
Ages	20 Years
Accepts Healthy Volunteers	No
Contacts	Contact: YUMIN YEH, MD 886-6-2353535 i5485111@gmail.com
Location Countries	Taiwan

Administrative Information[ + expand ][ + ]

NCT Number	NCT01997775
Other Study ID Numbers	B-BR-102-039
Has Data Monitoring Committee	No
Information Provided By	National Cheng-Kung University Hospital
Study Sponsor	National Cheng-Kung University Hospital
Collaborators	Not Provided
Investigators	Principal Investigator: YUMIN YEH, MD NATIONAL CHENG-KUNG UNI. HOSP.
Verification Date	November 2013

Locations[ + expand ][ + ]