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

NCT07291297 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00138078ONC-SAR-2401
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this research study is to see how metformin, when used in combination with standard of care (SOC) treatment for metastatic (cancer that has spread) soft tissue sarcoma can improve patient outcomes.

Conditions

Sarcoma Metastatic; Sarcoma, Soft Tissue

Keywords

Advanced Unresectable or Metastatic Soft Tissue Sarcoma; Metformin Hydrochloride

Outcome Measures

Primary Outcomes (1)

• Number of participants surviving at 12 months

  12-month overall survival (OS) will be determined for each participant as a binary variable indicating whether the participant was surviving at 12 months after study enrollment. Failure occurs if the participant dies from any cause within 12 months of study enrollment (initiation of metformin).

  From date of metformin start to date of death, or censored at 12 months, whichever occurred first.

Secondary Outcomes (2)

• Overall survival (OS)

  From date of metformin start to date of death, or censored as described; assessed for approximately 5 years.

• Cancer specific survival

  From date of metformin start to date of death, or censored as described; assessed for approximately 5 years.

Other Outcomes (4)

• Metformin administration

  From start of metformin treatment until last dose of study treatment; approximately 5 years

• Number of participants with at least one adverse event attributable to metformin

  From start of metformin treatment until 30 days after last dose of study treatment; approximately 5 years

• Number of participants with at least one serious adverse event

  From start of metformin treatment until 30 days after last dose of study treatment; approximately 5 years

Study Arms (1)

Metformin Hydrochloride ER

OTHER

1000mg early release (ER) of metformin by mouth daily for 14 days, in combination with physician directed SOC systemic therapy for advanced unresectable or metastatic STS. Toleration of the starting dose of metformin at 1000mg ER daily will be assessed during an office visit with the treating provider prior to Course1-D15. If toleration has been deemed acceptable, the metformin dose will be increased from 1000mg ER daily to 1000mg ER twice a day starting on Course1-D15. If the participant does not meet all criteria for dose escalation, the participant will continue to receive 1000mg ER daily.

Drug: Metformin Hydrochloride ER

Interventions

Metformin Hydrochloride ER DRUG

Participants will initially take 1000mg ER of metformin by mouth daily for 14 days, in combination with physician directed SOC systemic therapy for advanced unresectable or metastatic STS.

Metformin Hydrochloride ER

Eligibility Criteria

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

You may qualify if:

• Advanced unresectable or metastatic/intermediate/high grade soft tissue sarcoma
• Age ≥ 18 years at the time of enrollment
• Initiating first line systemic therapy for advanced/metastatic disease (treatment naïve for advanced/metastatic disease)
• Participants who have not yet initiated first line systemic therapy: expected to initiate front-line therapy within 4 weeks of initiating metformin
• Participants who have previously initiated first line systemic therapy: No more than 4 weeks from initiation of first line systemic therapy
• Adequate performance status (PS) defined as ECOG PS = 0-2
• Adequate renal function
• Adequate liver function
• 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.
• 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.
• 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.
• Ability to ingest oral medications

You may not qualify if:

• Already prescribed and taking metformin at time of diagnosis of advanced unresectable or metastatic disease
• Planned enrollment on a treatment clinical trial for first line therapy
• 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.
• History of acute or chronic metabolic acidosis including diabetic ketoacidosis, with or without coma.
• 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.
• Treatment with any investigational drug within 14 days prior to day 1 of treatment
• 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.
• 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.
• Patients with known brain or active central nervous system (CNS) metastases.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• Atrium Health Levine Cancer Institute: collaborator
• Paula Takacs Foundation: collaborator

Study Sites (2)

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

RECRUITING

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27103, United States

RECRUITING

MeSH Terms

Conditions

Sarcoma

Interventions

Metformin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Megan Jagosky, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Leah Wilson, RN

CONTACT

980-442-2333; Leah.J.Wilson@advocatehealth.org

Megan Jagosky, MD

CONTACT

704-446-1242; Megan.Jagosky@advocatehealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single Arm, Metformin

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: December 18, 2025
• Study Start: March 4, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2033
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (2)