Metformin in Stage IV Lung Adenocarcinoma

NCT ID: NCT01997775

Last Updated: 2016-09-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-31
• Study Completion Date: 2016-06-30

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.

Conditions

Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

METFORMIN

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

GLUCOPHAGE

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cheng-Kung University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yu-Min Yeh

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

YUMIN YEH, MD

Role: PRINCIPAL_INVESTIGATOR

NATIONAL CHENG-KUNG UNI. HOSP.

Locations

National Cheng-Kung Uni. Hosp.

Tainan City, , Taiwan

Countries

Taiwan

Other Identifiers

B-BR-102-039

Identifier Type: -

Identifier Source: org_study_id