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Effects of Metformin Hydrochloride in Participants with Malignant Solid Tumors

Trial Status: Active

This early phase I trial studies the effects of metformin hydrochloride in participants with malignant solid tumors. Metformin, a drug typically used for the treatment of diabetes, may help to reduce the growth of cancerous tumor cells in participants with malignant solid tumors.

Inclusion Criteria

  • Invasive malignant solid tumor of thoracic origin (e.g., lung, esophageal, thymus, mesothelioma, chest wall, mediastinum, trachea, pleura) with the intent to treat or biopsy by surgery as standard of care. Tumor must be >= 2 cm
  • Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes
  • Patients with type 2 diabetes mellitus (T2DM) being treated with metformin (any dose) for a clinical indication at the time of study enrollment are eligible, and will continue metformin treatment as clinically indicated during the presurgical study period. Their dose of metformin will NOT be changed
  • Patients not on metformin at the time of study entry must be willing to take metformin extended release (Glucophage XR, 750 mg QD for 4 days, then 750 mg BID for 3-6 days) for a total of 7-10 days prior to surgery * Patients do not require a diagnosis of diabetes to be enrolled in the study
  • All patients must be willing to keep a drug diary indicating the dates and times of metformin administration
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 75,000/mm^3
  • Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
  • Estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m^2 or estimated creatinine clearance (eCrCL) > 60 mL/min
  • Low-density lipoprotein (LDL) question for lung surgery do we need an international normalized ratio (INR) < 1.6
  • Ability to give informed consent
  • Patients must be willing to provide 20 mL of blood for research use
  • Patient must be willing to provide consent for use of archived tissue for research

Exclusion Criteria

  • History of diabetes that is currently being treated without metformin
  • Patients who, at the time of study entry, are not taking metformin for a clinical indication, and who will need a radiographic analysis with an iodinated contrast agent during the metformin study treatment period
  • This criterion does not apply to patients taking clinically indicated metformin at the time of study entry
  • History of reactive hypoglycemia
  • History of liver disease as defined with liver function tests (LFTs) above those in the inclusion
  • Known hypersensitivity to metformin
  • Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis
  • Patients who are pregnant or breastfeeding

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: ACTIVE
Contact: Joseph D Phillips
Phone: 603-650-8537

PRIMARY OBJECTIVES:

I. To determine the intra-tumor concentrations of metformin, with a standard deviation =< 25% of the mean, in patients with solid tumors of thoracic origin administered metformin extended release.

SECONDARY OBJECTIVES:

I. To determine the concentration of metformin in adipose tissue, tumor-adjacent normal tissue, plasma, and whole blood.

EXPLORATORY OBJECTIVES:

I. To determine whether metformin alters AMP-activated protein kinase (AMPK) activity in tumor cells.

OUTLINE:

Participants receive metformin hydrochloride orally (PO) once daily (QD) on days 1-4 and then twice daily (BID) on days 5-10 for 7-10 days prior to surgery in the absence of disease progression or unacceptable toxicity.

Trial Phase Phase O

Trial Type Basic science

Lead Organization
Dartmouth Hitchcock Medical Center

Principal Investigator
Joseph D Phillips

  • Primary ID D17188
  • Secondary IDs NCI-2018-01305, cphs 30872
  • Clinicaltrials.gov ID NCT03477162