NSCLCPhase 2CGMTNCT01864681
Combination of Metformin With Gefitinib to Treat NSCLC
A Phase 2 study testing Gefitinib and Metformin in people with NSCLC and EGFR Gene Amplification, run by Daping Hospital and the Research Institute of Surgery of the Third Military Medical University at 1 site in China.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- NSCLC, EGFR Gene Amplification, Advanced Cancer
- What is being tested?
- Gefitinib and Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 224 participants
- Where
- 1 siteChina
- Study dates
- May 2013to 4 Jun 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Respiratory Diseases, Daping Hospital, Third Military Medical University
Chongqing, Chongqing Municipality, 400042
About this study
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
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
Read the 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:
- 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.
- 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:
- Disease progression,
- Intercurrent illness that prevents further administration of treatment,
- Unacceptable adverse events(s),
- Patient decides to withdraw from the study, or
- General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
- Being tested
- Gefitinib and Metformin, Gefitinib and placebo
- Keywords
- NSCLC, TKIs, Metformin, PFS, overall survival, IL-6
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gefitinib and MetforminDrug
Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.
Gefitinib and placeboDrug
Gefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | 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. Receives: Drug: Gefitinib and Metformin |
| Arm B | Placebo comparator | Gefitinib and placebo. Placebo was given to patients in the same way as that of metformin in Arm A. Receives: Drug: Gefitinib and placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
PFS
One year progression-free survival (PFS) of the patients.
Measured: 1 year
Secondary outcomes (1)
Response to therapy and overall survival
The response to therapy and overall survival of the patients.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startMay 2013
- Primary completionDec 2017
- Study completion4 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NSCLCStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 224 participants (actual)
Sponsor and investigators
- Lead sponsor
- Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yong He, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
- Investigators
- Yong He, MD, Principal investigator, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01864681
- Sponsor's protocol ID
- 2012XLC07
- Acronym
- CGMT
- Status last verified
- Jun 2018
- First submitted
- 25 May 2013
- Last updated
- 20 Jun 2018
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li KL, Li L, Zhang P, Kang J, Wang YB, Chen HY, He Y. A Multicenter Double-blind Phase II Study of Metformin With Gefitinib as First-line Therapy of Locally Advanced Non-Small-cell Lung Cancer. Clin Lung Cancer. 2017 May;18(3):340-343. doi: 10.1016/j.cllc.2016.12.003. Epub 2016 Dec 22.
PubMed 28065465
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01864681
- Acronym / sponsor ID
- CGMT / 2012XLC07
- Keywords
- NSCLC, TKIs, Metformin, PFS, overall survival, IL-6
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 224 participants (actual)
- Lead sponsor
- Daping Hospital and the Research Institute of Surgery of the Third Military Medical UniversityUniversity, hospital or other
- Study start
- May 2013 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- 4 Jun 2018 (actual)
- First posted
- 29 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- 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:
- Disease progression,
- Intercurrent illness that prevents further administration of treatment,
- Unacceptable adverse events(s),
- Patient decides to withdraw from the study, or
- General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Gefitinib and MetforminGefitinib 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. |
| Arm B | Placebo comparator | Drug: Gefitinib and placeboGefitinib and placebo. Placebo was given to patients in the same way as that of metformin in Arm A. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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%).
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Gefitinib and MetforminGefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity. | Drug | Arm A |
| Gefitinib and placeboGefitinib will be administered once every day. If subject has complete response, partial response, stable disease, or unacceptable toxicity. | Drug | Arm B |
Primary outcome
PFS
Time frame: 1 year
One year progression-free survival (PFS) of the patients.
1 secondary outcome
Response to therapy and overall survival
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2018.
- Derived from this study: PubMed 28065465Li KL, Li L, Zhang P, Kang J, Wang YB, Chen HY, He Y. A Multicenter Double-blind Phase II Study of Metformin With Gefitinib as First-line Therapy of Locally Advanced Non-Small-cell Lung Cancer. Clin Lung Cancer. 2017 May;18(3):340-343. doi: 10.1016/j.cllc.2016.12.003. Epub 2016 Dec 22.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yong He, MD principal investigator
Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gefitinib and Metformin in people with NSCLC and EGFR Gene Amplification, run by Daping Hospital and the Research Institute of Surgery of the Third Military Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PFS (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01864681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2018.