Phase II Lung Metcore - Preoperative Metformin for Lung Cancer

NCT03086733 | Completed Phase 2 DMC

• 1 other identifier: 15-9560.0 - Lung Metcore Study
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Non Small Cell Lung Cancer; Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Ki67

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

  45 days after surgery

• Apoptosis

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

  45 days after surgery

Secondary Outcomes (2)

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

  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

• Pathology

  45 days after surgery

Study Arms (1)

Metformin

EXPERIMENTAL

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

Interventions

Metformin DRUG

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

Also known as: Glucophage

Metformin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Tom Waddell, MD

  Head of Thoracic Surgery Division

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: single center, open label, single arm Phase II study of a pre-operative window of metformin treatment in stages I - IIIA NSCLC

Study Record Dates

• First Submitted: February 24, 2017
• First Posted: March 22, 2017
• Study Start: December 5, 2016
• Primary Completion: July 1, 2020
• Study Completion: August 1, 2020
• Last Updated: August 19, 2020

Record last verified: 2020-08

Locations

CA (2)