Metformin Pharmacology in Human Cancers: A Proof of Principle Study

NCT03477162 | Terminated Early Phase 1 Results DMC FDA Drug

• 1 other identifier: D17188
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Thoracic Neoplasm

Outcome Measures

Primary Outcomes (1)

• Lung Tumor Tissue Concentration of Metformin

  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.

  Within 7 days from surgery

Secondary Outcomes (4)

• Concentration of Metformin in Adipose Tissue

  Within 7 days from surgery

• Concentration of Metformin in Tumor-adjacent Normal Tissue

  Within 7 days from surgery

• Concentration of Metformin in Plasma.

  Within 7 days from surgery

• Concentration of Metformin in Whole Blood.

  Within 7 days from surgery

Other Outcomes (1)

• AMPK Activity Alterations.

  Within 7 days from surgery.

Study Arms (1)

Metformin

EXPERIMENTAL

Patients enrolled will be treated with metformin (administered orally; 750 mg QD for 4 days, then 750 mg BID for 3-6 days; or clinically indicated metformin) for a total of 7-10 days prior to surgery, up until the night before surgery.

Drug: Metformin

Interventions

Metformin DRUG

Metformin will be given to patients prior to surgery.

Metformin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 centimeters (cm).
• Patients with multicentric disease are eligible. Samples from all available tumors are requested for research purposes.
• Patients with Type 2 diabetes mellitus 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.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) greater than or equal to 1,500/mm3 and platelet count greater than or equal to 75,000/mm3.
• Total bilirubin less than or equal to 1.5x the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3x ULN.
• Estimated glomerular filtration rate (eGFR) \> 60 mL/min/1.73m2 or estimated creatinine clearance (eCrCL) \> 60 mL/min
• Ability to give informed consent.
• Patients must be willing to provide 20 milliliters (mL) of blood for research use.
• Patient must be willing to provide consent for use of archived tissue for research.

You may not qualify if:

• 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.
• Known hypersensitivity to metformin.
• History of reactive hypoglycemia.
• Active or history of lactic acidosis, metabolic acidosis, or diabetic ketoacidosis.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

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MeSH Terms

Conditions

Thoracic Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Joseph Phillips, MD
• Organization: Dartmouth Hitchcock Medical Center

Joseph.D.Phillips@hitchcock.org

603-650-5000

Study Officials

• Joseph Phillips, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician, Thoracic Surgery

Study Record Dates

• First Submitted: March 14, 2018
• First Posted: March 26, 2018
• Study Start: May 15, 2018
• Primary Completion: November 30, 2021
• Study Completion: November 30, 2021
• Last Updated: October 3, 2023
• Results First Posted: October 3, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)