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Metformin in Stage IV Lung Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT01997775
Recruitment Status : Terminated (Difficult enrollment)
First Posted : November 28, 2013
Last Update Posted : September 30, 2016
Sponsor:
Information provided by (Responsible Party):
Yu-Min Yeh, National Cheng-Kung University Hospital

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

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: METFORMIN Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : August 2013
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
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.
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 Name: GLUCOPHAGE




Primary Outcome Measures :
  1. The change of plasma IL-6 level after the treatment with metformin [ Time Frame: 12 weeks ]

Secondary Outcome Measures :
  1. The objective response rate (RR) [ Time Frame: 2 YEARS ]
  2. The progression free survival [ Time Frame: 2 years ]
  3. The overall survival [ Time Frame: 2-years ]
  4. Number of participants with adverse events [ Time Frame: 2-years ]
    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.

  5. Changes of quality of life [ Time Frame: 2-years ]
    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



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Ages Eligible for Study:   20 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT01997775


Locations
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Taiwan
National Cheng-Kung Uni. Hosp.
Tainan, Taiwan, 704
Sponsors and Collaborators
National Cheng-Kung University Hospital
Investigators
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Principal Investigator: YUMIN YEH, MD NATIONAL CHENG-KUNG UNI. HOSP.

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Responsible Party: Yu-Min Yeh, MD, National Cheng-Kung University Hospital
ClinicalTrials.gov Identifier: NCT01997775     History of Changes
Other Study ID Numbers: B-BR-102-039
First Posted: November 28, 2013    Key Record Dates
Last Update Posted: September 30, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Yu-Min Yeh, National Cheng-Kung University Hospital:
IL-6
Metformin
Non-small cell lung cancer
Lung adenocarcinoma

Additional relevant MeSH terms:
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Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Bronchial Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Metformin
Hypoglycemic Agents
Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Adenocarcinoma of Lung
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Carcinoma
Physiological Effects of Drugs