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Combination of Metformin With Gefitinib to Treat NSCLC (CGMT)

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ClinicalTrials.gov Identifier: NCT01864681
Recruitment Status : Completed
First Posted : May 29, 2013
Last Update Posted : June 20, 2018
Sponsor:
Information provided by (Responsible Party):
Yong He, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Brief Summary:
The purpose of this study is to determine whether metformin in combination with gefitinib are effective in patients with previously untreated advanced or metastatic Non-Small-Cell Lung cancer with epidermal growth factor receptor (EGFR) mutations

Condition or disease Intervention/treatment Phase
NSCLC EGFR Gene Amplification Advanced Cancer Stage IIIB NSCLC Stage IV NSCLC Drug: Gefitinib and Metformin Drug: Gefitinib and placebo Phase 2

Detailed Description:

Primary Objectives: To determine the 1 year progression-free survival (PFS) of the combination of metformin and gefitinib in patients who harbors EGFR-mutant with previously untreated advanced or metastatic pulmonary adenocarcinoma.

Secondary Objectives:

A. To evaluate the response to therapy and overall survival of the combination of metformin with gefitinib in patients who harbors EGFR-mutant with previously untreated advanced or metastatic pulmonary adenocarcinoma.

B. To acquire preliminary data regarding the effects of metformin on interleukin-6 (IL-6) levels in tumor and serum.

Treatment will be administered on an outpatient basis. Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning gefitinib, if possible, but gefitinib administration will not be delayed for metformin loading.

Gefitinib will be administered 250mg QD continuously. Metformin will be administered continuously, beginning one week before beginning gefitinib, if possible, but tyrosine kinase inhibitors (TKI) will not be delayed for metformin loading.

Maintenance Therapy Patients responding to this therapy will be maintained with metformin (1000 mg twice daily) and gefitinib.

Duration of Therapy

In the absence of treatment delays due to adverse events, treatment may continue until one of the following criteria applies:

  1. Disease progression,
  2. Intercurrent illness that prevents further administration of treatment,
  3. Unacceptable adverse events(s),
  4. Patient decides to withdraw from the study, or
  5. General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 224 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Placebo Controlled Study to Evaluate the Efficacy of the Combination of Gefitinib and Metformin in Patients With Locally Advanced and Metastatic Non-Small-Cell-Lung-Cancer
Actual Study Start Date : May 2013
Actual Primary Completion Date : December 2017
Actual Study Completion Date : June 4, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A
Gefitinib and metformin. Metformin starting at a dose of 500 mg twice a day, orally with meals. After one week, increase the dose of metformin to 1000 mg as the first dose of the day and 500 mg as the second dose. After another week, increase to 1000 mg of metformin two times a day. Metformin treatment will be initiated one week before beginning TKI therapy, if possible, but TKI therapy will not be delayed for metformin loading.
Drug: Gefitinib and Metformin
Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.

Placebo Comparator: Arm B
Gefitinib and placebo. Placebo was given to patients in the same way as that of metformin in Arm A.
Drug: Gefitinib and placebo
Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.




Primary Outcome Measures :
  1. PFS [ Time Frame: 1 year ]
    One year progression-free survival (PFS) of the patients.


Secondary Outcome Measures :
  1. Response to therapy and overall survival [ Time Frame: 2 years ]
    The response to therapy and overall survival of the patients.


Other Outcome Measures:
  1. IL-6 level [ Time Frame: 2 years ]
    IL-6 level in tumors and blood serum of patients.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have Histologically or cytologically confirmed non small cell carcinoma of the lung who harbors EGFR-mutation and are previously untreated
  • Patient must have measurable stage IV disease (includes M1a, M1b stages or recurrent disease) (according to the 7th edition of the tumor node metastasis (TNM) classification system). However, patients with T4NX disease (stage III B) with nodule(s) in ipsilateral lung lobe are not eligible, because such patients were not included in historical controls.
  • Patients be age >18 years and < 75 years.
  • Patients must have a Life Expectancy of greater than 12 weeks.
  • Patients must have an electrocorticography (ECOG) performance status 0 or 1 (Karnofsky > 70%).
  • Patients must have normal organ and marrow function as defined below, within one week prior to randomization:

absolute neutrophil count >1,500/mL platelets > 100,000/mL total bilirubin: within normal institutional limits AST(SGOT)/ALT(SGPT) < 2.5 X institutional upper limit of normal creatinine ≤ 1.5 X institutional upper limit of normal urine dipstick for proteinuria of < less than 1+. If urine dipstick is > 1+ then a 24 hour urine for protein must demonstrate < 500 mg of protein in 24 hours to allow participation in the study.

  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Patients must have an international normalized ratio (INR) < 1.5 and a partial thromboplastin time (PTT) no greater than upper limits of normal within 1 week prior to randomization.
  • Patients with a history of hypertension must be well-controlled (<150 systolic/<100 diastolic) on a stable regimen of anti-hypertensive therapy.
  • Patients must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
  • Patients receiving chronic daily treatment with aspirin (> 325 mg/day) or nonsteroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole (Persantine), ticlopidine (Ticlid), clopidogrel (Plavix) and/or cilostazol (Pletal)is also not allowed.
  • Patients receiving therapeutic anticoagulation. Prophylactic anticoagulation of venous access devices is allowed provided Section 3.10 is met. Caution should be taken on treating patients with low dose heparin or low molecular weight heparin for DVT prophylaxis during treatment with bevacizumab as there may be an increased risk of bleeding.
  • Prior use of chemotherapy.
  • Patients receiving immunotherapy, hormonal-therapy and or radiotherapy within 2 weeks prior to entering the study. Note: Those who have not recovered from adverse events due to these agents administered will be considered ineligible.
  • Patients receiving any other investigational agents.
  • Patients with uncontrolled brain metastasis. Note: Patients with brain metastases must have stable neurologic status following local therapy (surgery or radiation) for at least 2 weeks, and must be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
  • Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin and paclitaxel or other agents used in the study are excluded.
  • Women that are pregnant or breastfeeding Note: Pregnant women are excluded from this study because the agents used in this study may be teratogenic to a fetus. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with paclitaxel, breastfeeding women are also excluded from this study.
  • Patients that are HIV-positive on combination antiretroviral therapy due to the potential for lethal infections when treated with marrow-suppressive therapy.

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): NCT01864681


Locations
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China, Chongqing
Department of Respiratory Diseases, Daping Hospital, Third Military Medical University
Chongqing, Chongqing, China, 400042
Sponsors and Collaborators
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
Investigators
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Principal Investigator: Yong He, MD Daping Hospital, Third Military Medical University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Yong He, Director of Department of Respiratory Diseases, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
ClinicalTrials.gov Identifier: NCT01864681     History of Changes
Other Study ID Numbers: 2012XLC07
First Posted: May 29, 2013    Key Record Dates
Last Update Posted: June 20, 2018
Last Verified: June 2018
Keywords provided by Yong He, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University:
NSCLC
TKIs
Metformin
PFS
overall survival
IL-6
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Metformin
Gefitinib
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action