Phase II Lung Metcore - Preoperative Metformin for Lung Cancer (Metcore)

• ClinicalTrials.gov Identifier: NCT03086733
• Recruitment Status: Recruiting
• First Posted: March 22, 2017
• Last Update Posted: October 11, 2018
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Study Description

Brief 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.

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer; Lung Cancer	Drug: Metformin	Phase 2

  Show Detailed Description

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 50 participants
• Intervention Model: Single Group Assignment
• Intervention 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)
• Primary Purpose: Treatment
• 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'
• Actual Study Start Date: December 5, 2016
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Metformin; 14 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.	Drug: Metformin; 850 mg tablets v/o OD for first 5 days 850 mg tablets v/o BID until day 21; Other Name: Glucophage

Outcome Measures

Primary Outcome Measures :

1. Ki67 [ Time Frame: 45 days after surgery ]
   • The difference in the proportion of proliferating NSCLC cells (measured by comparing Ki67 levels) prior to and after metformin treatment.
2. Apoptosis [ Time Frame: 45 days after surgery ]
   • The rate of apoptosis of NSCLC (measured by the TUNEL assay) prior to and after metformin treatment.

Secondary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 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 ]
   • 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])
2. Pathology [ Time Frame: 45 days after surgery ]
   • Pathologic changes in lung tissue after metformin administration

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• 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:

  • 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.

Exclusion Criteria:

• 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:

  • 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.

Contacts and Locations

Contacts

Contact: Natasha Leighl, MD; 1416-946-2858; natasha.leighl@uhn.ca

Contact: Thomas Waddell, MD; 1416-340-3432; tom.waddell@uhn.ca

Locations

Canada, Ontario

Toronto General Hospital; Recruiting

Toronto, Ontario, Canada, M5G 2C4

Contact: Alexandra Salvarrey, MD MSc 1-416-340-4800 ext 6992 alexandra.salvarrey@uhn.on.ca

Contact: Jennifer Lister, BSc 1-416-340-4800 ext 4857 jennifer.lister@uhn.on.ca

Principal Investigator: Thomas Waddell, MD FRCSC

Princess Margaret Hospital; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Contact: Alexandra Salvarrey, MD MSc 1-416-946-4501 ext 5444 alexandra.salvarrey@uhn.on.ca

Contact: Jennifer Lister, BSc 1-416-340-4800 ext 4857 jennifer.lister@uhn.on.ca

Principal Investigator: Natasha Leighl, MD MSc FRCPC

Sponsors and Collaborators

University Health Network, Toronto

Investigators

• Principal Investigator: Tom Waddell, MD; Head of Thoracic Surgery Division

More Information

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT03086733 History of Changes
• Other Study ID Numbers: 15-9560.0 - Lung Metcore Study
• First Posted: March 22, 2017
• Last Update Posted: October 11, 2018
• Last Verified: October 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by University Health Network, Toronto:

Lung Cancer; Non small cell lung cancer; Metformin; Pre-operative treatment; Neoadjuvant treatments; Cancer; Phase II

Additional relevant MeSH terms:

Lung Diseases; Metformin; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs