A phase I dose-escalation and metabolomics study of metformin combined with chemotherapy and/or immunotherapy in solid malignancies

Cancer Categories

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Primary Objectives:

Evaluate the dose limiting toxicities (DLTs) of metformin alone and in combination with chemotherapy and/or immunotherapy (IO) in patients with solid malignancies
Determine the maximum tolerated dose (MTD) of metformin in combination with chemotherapy and/or IO in patients with solid malignancies

Secondary Objective:

Eligibility

Inclusion Criteria:

Have histologically confirmed advanced solid tumor and are considered a suitable candidate for chemotherapy and/or immunotherapy or both
Are a male or female participant aged ≥ 18 years
Have provided a signed, written informed consent form
Have measurable disease per RECIST v1.1
Have adequate hematologic, renal, liver, and coagulation function as defined by the following:

Hemoglobin ≥ 8 g/dL if determined suitable by the investigator for the selected chemotherapy and/or immunotherapy regimen for the particular patient
Absolute neutrophil count (ANC) > 1500/mm3
Platelets > 75,000/mm3 if determined suitable by the investigator for the selected chemotherapy and /or immunotherapy regimen for the particular patient
Estimated Glomerular Filtration Rate (eGFR) > 45 mL/min/1.73 m2 (as described by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] 2021 equation)
Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Participants with known Gilbert's syndrome who have total bilirubin level ≤ 3 x ULN may be enrolled if deemed suitable for a particular patient by the investigator for the selected chemotherapy and/or immunotherapy regimen.
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 x ULN. For participants with hepatic metastases, AST and ALT ≤ 5 x ULN.
Alkaline phosphatase (ALP) < 2.5 x ULN. For participants with hepatic and/or bone metastases ≤ 5 x ULN

Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, and suitable for chemotherapy/IO recommended by the investigator.
Participants who have experienced expected toxicity from Cycle 1 of anticancer therapy which is unlikely to recover to grade 1 or better prior to Cycle 2 (e.g., anemia, alopecia, vitiligo, endocrine dysfunction associated with IO) and may otherwise not impact the eligibility will be allowed.
Women of child-bearing potential must agree to avoid becoming pregnant and male participants should avoid impregnating a female partner or donating sperm starting at initiation of treatment up until at least 90 days after the last dose of study drug.
Have an estimated life expectancy of at least 12 weeks

Exclusion Criteria:

Patients who have or are any of the following exclusion criteria are not eligible for participation in the study.
Patients with uncontrolled diabetes
Patients who have received metformin must be at least five half-lives beyond such treatment (four weeks) and must not be taking metformin at the time of enrollment.
Patients with a known hypersensitivity to metformin, its excipients, its analogs, or any of its components
Patients on other antidiabetic medicines are eligible as long as adding metformin will not be contraindicated
Patients with an inability to tolerate oral medications
Women who are pregnant or lactating
Patients with clinically significant intercurrent disease including, but not limited to:

New York Heart Association Class III or IV heart failure
Myocardial infarction, unstable angina, or stroke ≤ 3 months prior to Cycle 1 Day 1
Uncontrolled arrhythmia
Clinically significant active infection requiring IV antibiotic, antiviral, or antifungal medications

Patients with other current medical or other conditions that, in the opinion of the investigator, may confound study interpretation or prevent completion of study procedures and follow-up examinations
Patients with an unwillingness or inability to comply with the study procedures required in this protocol
Patients using an investigational agent within four weeks of study entry

Locations

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices