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Non Small Cell Lung CancerPhase 2MetcoreNCT03086733

Phase II Lung Metcore - Preoperative Metformin for Lung Cancer

A Phase 2 study testing Metformin in people with Non Small Cell Lung Cancer and Lung Cancer, run by University Health Network, Toronto at 2 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase II single centre open label single arm pre-operative window of metformin treatment in stage I-IIIa Non small cell lung cancer. In which patients will be invited to participate by receiving Metformin treatment during 14 to 21 days at 850 mg BID until the day before surgery. Read more about this study

Who is it for?
Ages 18 to 90 yearsHealthy volunteers can take part
Conditions the study is for
Non Small Cell Lung Cancer, Lung Cancer
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
2 sitesCanada
Study dates
5 Dec 2016to Aug 2020
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 90 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Have biopsy-proven non-small cell lung carcinoma (NSCLC) of any histological variant except for neuroendocrine tumors. Patients must not have mixed NSCLC and small cell lung cancer (SCLC).
  • Be of clinical stage I to IIIA (according to the 7th lung cancer TNM classification and staging system) by radiologic and/or pathologic criteria where appropriate (e.g. mediastinoscopic staging). Baseline CT-chest scan must be within 4 weeks of study entry.
  • Be deemed appropriate candidates for surgical resection by the treating surgeon and assessing team.
  • Be aged - 18 years or more.
  • Have ECOG performance status - 2.
  • Have organ and marrow function as defined below for safe lung biopsy and administration of metformin:
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  • Platelets -100 000
  • Total bilirubin -1.5 X institutional upper limit of normal
  • AST/ALT -2 X institutional upper limit of normal
  • Creatinine clearance -60 mL/min/1.73 m2
  • Have the ability to understand and the willingness to sign a written informed consent document.
  • Not require emergency surgery within 14 days of staging investigations.
  • Not have received anticancer treatment with chemotherapy, radiotherapy or Epidermal - - Growth Factor Receptor (EGFR) inhibitor therapy for the current lung cancer.
  • Not have a concomitant active malignancy or be receiving any other investigational or anticancer agents while on the study, to avoid the influence of alternative anti-cancer therapy. Otherwise, those with a past history of cancer are eligible.

Who cannot join

  • Not have a past history of an allergic reaction to metformin.
  • Not have a past history of diabetes mellitus or fasting glucose ≥ 7.0 mmol/L.
  • Not have a past history of lactic acidosis or metabolic acidosis.
  • Not have consumption of ≥ 3 alcoholic beverages per day (average).
  • Not have had regular use of agents that may influence insulin sensitivity/levels within 4 weeks of study entry.
  • Not have uncontrolled intercurrent illness (es) including but not limited to: ongoing or active:
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  • Infection,
  • Symptomatic congestive
  • Cardiac failure or evidence of cardiac dysfunction,
  • Unstable angina pectoris,
  • Cardiac arrhythmia,
  • Active peptic ulcer disease or gastrointestinal conditions (e.g. Inflammatory bowel disease) or
  • Psychiatric illness/social situations that would limit compliance with study requirements.
  • Not be on a loop diuretic due to their potential to cause renal impairment and predispose to lactic acidosis.
  • Not have contrast-enhanced imaging (except when clinically indicated) while on the study. Iodinated contrast agents can cause renal failure, leading to metformin accumulation and lactic acidosis.
  • Women should not be pregnant or become pregnant during study.

Trial locations and contacts

2 sites in 1 country.

Canada2 sites

  • Toronto General Hospital

    Toronto, Ontario, M5G 2C4

  • Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

Other trials in Canada

About this study

Official title: Phase II Study of Single Agent Pre-operative Metformin in Patients With Clinical Stage I - IIIA NSCLC Proceeding to Surgical Resection. 'Lung Metcore Study'

This is a phase II single centre open label single arm pre-operative window of metformin treatment in stage I-IIIa Non small cell lung cancer.

In which patients will be invited to participate by receiving Metformin treatment during 14 to 21 days at 850 mg BID until the day before surgery.

They will be followed closely for any Adverse Events during treatment and 30 days after surgery. During treatment there will be no follow up tests except 1 fasting blood glucose at week 2 of treatment.

Survival data will be prospectively gathered after study treatment has ended until death.

Read the detailed description

Title of study: Phase II study of single agent pre-operative metformin in patients with clinical stage I - IIIA NSCLC proceeding to surgical resection. 'Lung Metcore Study'

Objectives:

To evaluate the effects of short-term pre-operative exposure to metformin in operable stages I to IIIA NSCLC.

Primary end-points:

  • The difference in the proportion of proliferating NSCLC cells (measured by comparing Ki67 levels) prior to and after metformin treatment.
  • The rate of apoptosis of NSCLC (measured by the TUNEL assay) prior to and after metformin treatment.

Secondary end-points:

  • The safety and tolerability of preoperative metformin administration in NSCLC, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE [version 4.0])
  • Pathologic changes in lung tissue after metformin administration. Study Design: This trial is designed as a single center, open label, single arm Phase II study of a pre-operative window of metformin treatment in stages I - IIIA NSCLC. The efficacy of metformin will be assessed by its effects on markers of cellular proliferation and apoptosis. Exploratory analysis of molecular markers of the hypothesized effects of metformin in NSCLC will also be carried out. Furthermore, changes in serum ligands to growth signaling pathways in lung cancer with metformin treatment will be measured.

Number of patients: Thus, the total expected sample size is approximately 50 patients, anticipating minimal loss of eligible participants through treatment intolerance or acceleration of surgery. Accrual is estimated at 1.5 to 2 patients per month for 25 to 33 months, based on accrual rates for a recent pre-operative window thoracic surgical study at UHN.

  • Metformin will be started at a dose of 850mg daily then increased to 850mg b.i.d. (morning and evening) after 5 days as tolerated. Treatment will be given from the time of enrollment till the evening prior to surgery.

Correlatives:

The following molecular and serological correlative biomarkers will be considered covariates in the analysis of primary endpoints of the phase II study. Covariate pretreatment values and changes in covariate values (where applicable) will be used to estimate the relationship between covariates and patient's Ki67 or apoptotic response using logistic regression. It is noted that several covariates are being tested and the number of patients being analyzed is small, thus, some tests may be statistically significant due to chance even if no association exists.

  • Genetic Mutations in NSCLC (On pre-treatment biopsies by molecular techniques):
  • LKB1 mutational status (Sequencing)
  • EGFR, Ras, AKT, PI3K mutations (Oncocarta platform)
  • EGFR gene copy number (FISH)
  • ALK rearrangement status
  • Protein Marker of Resistance To Metformin (On pre-treatment biopsies by immunohistochemistry
  • OCT1 expression
  • PROTEIN MARKERS OF RECEPTORS AND ACTIVATED PATHWAYS TO mtor IN NSCLC (Comparison between pre-treatment biopsies and post-resection specimens by immunohistochemistry):
  • IR
  • IGF-1R
  • Phosphorylated-AMPK
  • EGFR and phospho-EGFR
  • PKB (AKT) and phospho-AKT
  • Phosphorylated (erbb2, erbb3, erbb4)
  • Phosphorylated-STAT3
  • Phospho-ribosomal protein S6
  • VASCULARITY IN NSCLC (Comparison between pre-treatment biopsies and post-resection specimens by immunohistochemistry):
  • VEGF
  • Microvessel density count (CD34, CD105)
  • SERUM LIGANDS TO SIGNALLING PATHWAYS IN NSCLC (Comparison between pre-treatment biopsies and post-resection specimens by ELISA):
  • Insulin
  • Glucose
  • IGF-1
  • TGF-α
  • TNF-α
  • Calculated HOMA
  • CRP
  • Adiponectin

Statistics:

Patients who completed metformin treatment will have the Ki67 and apoptosis scores compared between samples obtained pre and post-metformin treatment. Changes in Ki67 and apoptotic scores with metformin treatment will be correlated with the biomarkers of various pathways hypothesized to mediate an effect of metformin on NSCLC development.

Being tested
Metformin
Keywords
Lung Cancer, Non small cell lung cancer, Metformin, Pre-operative treatment, Neoadjuvant treatments, Cancer, Phase II
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Glucophage

    850 mg tablets v/o OD for first 5 days 850 mg tablets v/o BID until day 21

Study groups in NCT03086733
Study groupRoleWhat they receive
MetforminExperimental14 to 21 days of pre-operative Metformin tablets First 5 days 850 mg OD v/o 850 mg BID thereafter until 21 days are completed.
Receives: Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Ki67

    • The difference in the proportion of proliferating NSCLC cells (measured by comparing Ki67 levels) prior to and after metformin treatment.

    Measured: 45 days after surgery

  2. Apoptosis

    • The rate of apoptosis of NSCLC (measured by the TUNEL assay) prior to and after metformin treatment.

    Measured: 45 days after surgery

Secondary outcomes (2)

  1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

    • The safety and tolerability of preoperative metformin administration in NSCLC, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE [version 4.0])

    Measured: During a minimum of 14 days and maximum of 21 days patients will be assessed every 5 days during treatment and 30 days after surgery

  2. Pathology

    • Pathologic changes in lung tissue after metformin administration

    Measured: 45 days after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2017
  2. Study start5 Dec 2016
  3. Primary completionJul 2020
  4. Study completionAug 2020

Resources

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
Not applicable
Intervention model
Single group
Model description
single center, open label, single arm Phase II study of a pre-operative window of metformin treatment in stages I - IIIA NSCLC
Masking
None (open label)
Enrolment
28 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03086733
Sponsor's protocol ID
15-9560.0 - Lung Metcore Study
Acronym
Metcore
Status last verified
Aug 2020
First submitted
24 Feb 2017
Last updated
19 Aug 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Metformin in people with Non Small Cell Lung Cancer and Lung Cancer, run by University Health Network, Toronto at 2 sites in Canada.

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 14 inclusion and 16 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 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Canada. 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. 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?

Ki67 (time frame: 45 days after surgery). The study lists 2 primary outcomes in all. 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 NCT03086733.

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 19 Aug 2020.

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