Metformin plus standard first-line therapy for advanced soft tissue sarcoma

Metformin Hydrochloride in Combination With Standard of Care Systemic Therapy in Previously Untreated Advanced Unresectable or Metastatic Soft Tissue Sarcoma

This trial tests whether adding metformin to standard first-line systemic treatment helps people with previously untreated advanced or metastatic soft tissue sarcoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Wake Forest University Health Sciences (Academic / other)
• Locations: 2 sites (Charlotte, North Carolina and 1 other locations)
• Trial ID: NCT07291297 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label Phase II study testing extended-release metformin given alongside physician-directed standard-of-care first-line systemic therapy for adults with advanced unresectable or metastatic soft tissue sarcoma. Participants start metformin 1000 mg ER daily for 14 days and, if tolerated, escalate to 1000 mg ER twice daily beginning around Day 15, with tolerability assessed clinically and by organ-function tests. Treatment continues for up to five years or until early discontinuation, and metformin must begin within four weeks of initiating front-line systemic therapy. Eligible participants are adults with intermediate/high-grade advanced or metastatic soft tissue sarcoma, ECOG performance status 0–2, and adequate renal and hepatic function.

Who should consider this trial

Good fit: Adults (≥18) with previously untreated advanced unresectable or metastatic intermediate/high-grade soft tissue sarcoma who are starting first-line systemic therapy, have ECOG 0–2, and adequate kidney and liver function are ideal candidates.

Not a fit: Patients who have already received systemic therapy for metastatic disease, have poor organ function, significant renal impairment, cannot tolerate metformin, or are pregnant are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding metformin may improve clinical outcomes such as response rates or progression-free survival for patients with advanced soft tissue sarcoma.

How similar studies have performed: Metformin has shown mixed signals in other cancer types with some promising preclinical data, but randomized evidence specifically in advanced soft tissue sarcoma is very limited.

Eligibility criteria

Inclusion Criteria:

1. Advanced unresectable or metastatic/intermediate/high grade soft tissue sarcoma
2. Age ≥ 18 years at the time of enrollment
3. Initiating first line systemic therapy for advanced/metastatic disease (treatment naïve for advanced/metastatic disease)

   1. Participants who have not yet initiated first line systemic therapy: expected to initiate front-line therapy within 4 weeks of initiating metformin
   2. Participants who have previously initiated first line systemic therapy: No more than 4 weeks from initiation of first line systemic therapy
4. Adequate performance status (PS) defined as ECOG PS = 0-2
5. Adequate renal function
6. Adequate liver function
7. Individuals of childbearing potential (ICBP) must have a negative serum pregnancy test within 7 days prior to enrollment. NOTE: Individuals who may become pregnant are considered to have childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are postmenopausal (at least 12 consecutive months with no menses without an alternative medical cause). Metformin is known to be excreted in breast milk and should not be used by nursing mothers.
8. ICBP and partners of ICBP must not be expecting to conceive and be willing to use a highly effective contraceptive method (i.e., achieves a failure rate of \<1% per year when used consistently and correctly) from the time of informed consent until 30 days after study treatment discontinuation.
9. Individuals who are having sexual relationships in which their partners may become pregnant must be willing to use condoms from the time of informed consent until 30 days after study treatment discontinuation. For a non-pregnant ICBP partner, contraception recommendations should also be considered.
10. Ability to ingest oral medications

Exclusion Criteria:

1. Already prescribed and taking metformin at time of diagnosis of advanced unresectable or metastatic disease
2. Planned enrollment on a treatment clinical trial for first line therapy
3. Breastfeeding within the duration of anticipated study treatment. NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
4. History of acute or chronic metabolic acidosis including diabetic ketoacidosis, with or without coma.
5. Participants previously diagnosed with an additional malignancy must be disease-free for at least five years prior to enrollment. Exceptions include ductal carcinoma in situ (DCIS), basal cell or squamous cell skin cancer and in situ cervical or bladder cancer.
6. Treatment with any investigational drug within 14 days prior to day 1 of treatment
7. History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin. Participants receiving any medications or substances that are inhibitors or inducers of CYP450 enzyme(s) are ineligible. Lists including medications and substances known or with the potential to interact with the specified CYP450 enzyme(s) isoenzymes. Please refer to https://drug-interactions.medicine.iu.edu/MainTable.aspx for the most current information.
8. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure requiring pharmacologic treatment, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements as determined by the investigator.
9. Patients with known brain or active central nervous system (CNS) metastases.

Where this trial is running

Charlotte, North Carolina and 1 other locations

• Levine Cancer Institute — Charlotte, North Carolina, United States (Recruiting)
• Atrium Health Wake Forest Baptist Comprehensive Cancer Center — Winston-Salem, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Megan Jagosky, MD — Wake Forest University Health Sciences
• Study coordinator: Leah Wilson, RN

Conditions Sarcoma Metastatic; Sarcoma, Soft Tissue; Advanced Unresectable or Metastatic Soft Tissue Sarcoma; Metformin Hydrochloride