Back to results

Metformin in Stage IV Lung Adenocarcinoma

Primary Purpose

Non-small Cell Lung Cancer

Status

Terminated

Phase

Phase 2

Locations

Taiwan

Study Type

Interventional

Intervention

METFORMIN

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring IL-6, Metformin, Non-small cell lung cancer, Lung adenocarcinoma

Eligibility Criteria

20 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Histologically or cytologically confirmed lung adenocarcinoma.
Stage IV disease as defined by AJCC 7th edition staging.
At least one measurable lesion (as defined by RECIST v1.1).
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).
Age ≤ 80 years old and ≥ 20 years old.
ECOG performance status of 0-2.
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)
Estimated life expectancy of at least 6 months.
Written (signed) Informed Consent.

Exclusion Criteria:

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.
Use of other anti-cancer therapy, including chemotherapy, target therapy, immunotherapy, radiotherapy, and hormone therapy.
Prior participation in any investigational drug study within 28 days.
Use of anti-IL-6 or IL-6-lowering agents.
Use of metformin in the past 6 months.
Poor controlled diabetes (HbA1c ≥ 8.0%).
Known hypersensitivity or intolerance to metformin.
Congestive heart failure with NYHA functional class II~IV.
History of lactic acidosis.
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).
Active uncontrolled infections or HIV infection.
Psychiatric disorders that would compromise the patient's compliance or decision.
Current or planned pregnancy, or breast feeding in women.
Poor compliance.

Sites / Locations

National Cheng-Kung Uni. Hosp.

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

METFORMIN

Arm Description

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.

Outcomes

Primary Outcome Measures

The change of plasma IL-6 level after the treatment with metformin

Secondary Outcome Measures

The objective response rate (RR)

The progression free survival

The overall survival

Number of participants with adverse events

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

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

Full Information

NCT ID

NCT01997775

First Posted

November 17, 2013

Last Updated

September 29, 2016

Sponsor

National Cheng-Kung University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01997775

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2016

Overall Recruitment Status

Terminated

Why Stopped

Difficult enrollment

Study Start Date

August 2013 (undefined)

Primary Completion Date

June 2016 (Actual)

Study Completion Date

June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

National Cheng-Kung University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-small Cell Lung Cancer

Keywords

IL-6, Metformin, Non-small cell lung cancer, Lung adenocarcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

METFORMIN

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

METFORMIN

Other Intervention Name(s)

GLUCOPHAGE

Intervention Description

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.

Primary Outcome Measure Information:

Title

The change of plasma IL-6 level after the treatment with metformin

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

The objective response rate (RR)

Time Frame

2 YEARS

Title

The progression free survival

Time Frame

2 years

Title

The overall survival

Time Frame

2-years

Title

Number of participants with adverse events

Description

Time Frame

2-years

Title

Changes of quality of life

Description

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

Time Frame

2-years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Histologically or cytologically confirmed lung adenocarcinoma. Stage IV disease as defined by AJCC 7th edition staging. At least one measurable lesion (as defined by RECIST v1.1). 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). Age ≤ 80 years old and ≥ 20 years old. ECOG performance status of 0-2. 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) Estimated life expectancy of at least 6 months. Written (signed) Informed Consent. Exclusion Criteria: 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. Use of other anti-cancer therapy, including chemotherapy, target therapy, immunotherapy, radiotherapy, and hormone therapy. Prior participation in any investigational drug study within 28 days. Use of anti-IL-6 or IL-6-lowering agents. Use of metformin in the past 6 months. Poor controlled diabetes (HbA1c ≥ 8.0%). Known hypersensitivity or intolerance to metformin. Congestive heart failure with NYHA functional class II~IV. History of lactic acidosis. 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). Active uncontrolled infections or HIV infection. Psychiatric disorders that would compromise the patient's compliance or decision. Current or planned pregnancy, or breast feeding in women. Poor compliance.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

YUMIN YEH, MD

Organizational Affiliation

NATIONAL CHENG-KUNG UNI. HOSP.

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Cheng-Kung Uni. Hosp.

City

Tainan

ZIP/Postal Code

704

Country

Taiwan

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Metformin in Stage IV Lung Adenocarcinoma

We'll reach out to this number within 24 hrs