Metformin with chemotherapy and/or immunotherapy for advanced solid tumors

A Phase I Dose-escalation and Metabolomics Study of Metformin Combined With Chemotherapy and/or Immunotherapy in Solid Malignancies

This trial tests whether taking metformin alone and then together with standard chemotherapy and/or immunotherapy is safe for adults with advanced solid tumors.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Barbara Ann Karmanos Cancer Institute (other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Detroit, Michigan)
• Trial ID: NCT07098299 on ClinicalTrials.gov

What this trial studies

This is a Phase 1, single-site safety trial that gives participants metformin alone for 14 days between the first and second cycles of their planned chemotherapy and/or immunotherapy to assess tolerability, then continues metformin daily alongside standard treatment from cycle 2 onward. Multiple metformin dose levels will be tested to document toxicity profiles and to determine the maximum tolerated dose when combined with various systemic cancer therapies. Participants will otherwise receive standard-of-care chemotherapy and/or immunotherapy chosen for their disease and stage, with routine imaging and labs to monitor for adverse events and response. Safety endpoints and dose-limiting toxicities will guide dose escalation decisions and recommendations for future studies.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed advanced solid tumors who are candidates for systemic chemotherapy and/or immunotherapy and who meet organ function and blood count requirements are eligible.

Not a fit: Patients with inadequate kidney, liver, or bone marrow function, those not receiving systemic chemotherapy or immunotherapy, or those who cannot travel to the study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, this could establish a safe metformin dose to add to standard chemotherapy or immunotherapy and potentially allow further studies of whether it improves outcomes.

How similar studies have performed: Repurposing metformin in combination with cancer therapies has been tried in other early-phase studies with generally tolerable safety but mixed efficacy results, so the approach is not entirely novel but remains unproven.

Eligibility criteria

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:

  1. Hemoglobin ≥ 8 g/dL if determined suitable by the investigator for the selected chemotherapy and/or immunotherapy regimen for the particular patient
  2. Absolute neutrophil count (ANC) \> 1500/mm3
  3. Platelets \> 75,000/mm3 if determined suitable by the investigator for the selected chemotherapy and /or immunotherapy regimen for the particular patient
  4. Estimated Glomerular Filtration Rate (eGFR) \> 45 mL/min/1.73 m2 (as described by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] 2021 equation)
  5. 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.
  6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5 x ULN. For participants with hepatic metastases, AST and ALT ≤ 5 x ULN.
  7. 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:

  1. New York Heart Association Class III or IV heart failure
  2. Myocardial infarction, unstable angina, or stroke ≤ 3 months prior to Cycle 1 Day 1
  3. Uncontrolled arrhythmia
  4. 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
* Patients with uncontrolled metabolic disorders or primary or secondary effects of cancer that induce a high medical risk

Where this trial is running

Detroit, Michigan

• Karmanos Cancer Institute — Detroit, Michigan, United States (RECRUITING)

Study contacts

• Principal investigator: Wasif Saif, M.D. — Wayne State University
• Study coordinator: Wasif Saif, M.D.

Conditions: Advanced Solid Tumor