Clinical trial NCT01997775: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Keywords: IL-6
Metformin
Non-small cell lung cancer
Lung adenocarcinoma
Lead sponsor: National Cheng-Kung University Hospital
Sponsor class: OTHER
First posted: 2013-11-28
Enrollment: 13
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: The change of plasma IL-6 level after the treatment with metformin
timeFrame: 12 weeks
Secondary outcomes:
measure: The objective response rate (RR)
timeFrame: 2 YEARS
measure: The progression free survival
timeFrame: 2 years
measure: The overall survival
timeFrame: 2-years
measure: Number of participants with adverse events
timeFrame: 2-years
measure: Changes of quality of life
timeFrame: 2-years
Other outcomes:
Locations:
city: Tainan
country: Taiwan
facility: National Cheng-Kung Uni. Hosp.
Study officials:
affiliation: NATIONAL CHENG-KUNG UNI. HOSP.
name: YUMIN YEH, MD
role: PRINCIPAL_INVESTIGATOR
References: