NCT03477162

Metformin Pharmacology in Human Cancers: A Proof of Principle Study

Metformin Pharmacology in Human Cancers

• Status: Terminated
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 18 (actual)
• Sponsor: Dartmouth-Hitchcock Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a presurgical (proof of principle, window of opportunity) study in patients with surgically resectable thoracic tumors to determine steady-state tissue and plasma concentrations of metformin.

Detailed description

To understand the variability in clinical results testing metformin as an anti-cancer agent, it is important to determine the concentrations of metformin that are achievable in tissue. Clinical effects of metformin develop gradually over several days of treatment. Steady-state plasma metformin concentrations are correlated with anti-hyperglycemic response. Thus, achieving steady-state concentrations in this study will allow accurate determination of the most representative concentrations of metformin in normal and cancerous tissues, as well as determine AMP-activated protein kinase (AMPK) signaling differences in these tissues. As tha Primary Objective is to determine the concentration of metformin in tumors, patients will be treated with metformin extended release (ER) (Glucophage® XR), starting at 750 milligrams (mg) oral (PO) once daily (QD) for 4 days, then escalating to 750 mg PO twice daily (BID) for 3-6 days prior to surgery. FDA prescribing information indicates that metformin reaches steady-state plasma concentrations within 24-48 hours after the start of dosing in humans; thus, the 7-to-10-day time frame of this study will allow sufficient time for metformin to reach steady-state plasma concentrations, in addition to time allotted for potential accumulation in tissues. Metformin concentrations will be measured using a validated liquid chromatography-mass spectrometry (LC-MS/MS) assay.

Conditions

• Thoracic Neoplasm

Interventions

Type	Name	Description
DRUG	Metformin	Metformin will be given to patients prior to surgery.

Timeline

• Start date: 2018-05-15
• Primary completion: 2021-11-30
• Completion: 2021-11-30
• First posted: 2018-03-26
• Last updated: 2023-10-03
• Results posted: 2023-10-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study