Combination of Metformin With Gefitinib to Treat NSCLC

Overview[ - collapse ][ - ]

Purpose 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
ConditionNSCLC
EGFR Gene Amplification
Advanced Cancer
Stage IIIB NSCLC
Stage IV NSCLC
InterventionDrug: Gefitinib and Metformin
Drug: Gefitinib and placebo
PhasePhase 2
SponsorDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
Responsible PartyDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
ClinicalTrials.gov IdentifierNCT01864681
First ReceivedMay 25, 2013
Last UpdatedJune 2, 2013
Last verifiedJune 2013

Tracking Information[ + expand ][ + ]

First Received DateMay 25, 2013
Last Updated DateJune 2, 2013
Start DateMay 2013
Estimated Primary Completion DateMay 2017
Current Primary Outcome MeasuresPFS [Time Frame: 1 year] [Designated as safety issue: No]One year progression-free survival (PFS) of the patients.
Current Secondary Outcome MeasuresResponse to therapy and overall survival [Time Frame: 2 years] [Designated as safety issue: No]The response to therapy and overall survival of the patients.

Descriptive Information[ + expand ][ + ]

Brief TitleCombination of Metformin With Gefitinib to Treat NSCLC
Official TitleA 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
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
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.
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Condition
  • NSCLC
  • EGFR Gene Amplification
  • Advanced Cancer
  • Stage IIIB NSCLC
  • Stage IV NSCLC
InterventionDrug: Gefitinib and Metformin
Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.
Drug: Gefitinib and placebo
Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.
Study Arm (s)
  • 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.
  • Placebo Comparator: Arm B
    Gefitinib and placebo. Placebo was given to patients in the same way as that of metformin in Arm A.

Recruitment Information[ + expand ][ + ]

Recruitment StatusRecruiting
Estimated Enrollment168
Estimated Completion DateMay 2017
Estimated Primary Completion DateMay 2015
Eligibility 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.
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsContact: Yong He, MD
86-23-68757791
heyong@dphospital.tmmu.edu.cn
Location CountriesChina

Administrative Information[ + expand ][ + ]

NCT Number NCT01864681
Other Study ID Numbers2012XLC07
Has Data Monitoring CommitteeYes
Information Provided ByDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
Study SponsorDaping Hospital and the Research Institute of Surgery of the Third Military Medical University
CollaboratorsNot Provided
Investigators Principal Investigator: Yong He, MD Daping Hospital, Third Military Medical University
Verification DateJune 2013

Locations[ + expand ][ + ]

Department of Respiratory Diseases, Daping Hospital, Third Military Medical University
Chongqing, Chongqing, China, 400042
Contact: Yong He, MD | 86-23-68757791 | heyong@dphospital.tmmu.edu.cn
Principal Investigator: Yong He, MD
Recruiting