Sarcoma MetastaticPhase 2NCT07291297
Metformin Hydrochloride in Combination With Standard of Care Systemic Therapy in Previously Untreated Advanced Unresectable or Metastatic Soft Tissue Sarcoma
A Phase 2 study testing Metformin Hydrochloride ER in people with Sarcoma Metastatic and Sarcoma, Soft Tissue, run by Wake Forest University Health Sciences at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sarcoma Metastatic, Sarcoma, Soft Tissue
- What is being tested?
- Metformin Hydrochloride ER
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Mar 2026to Oct 2033
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Levine Cancer Institute
Charlotte, North Carolina, 28204
Leah Wilson, RN, 980-442-2333, Leah.J.Wilson@advocatehealth.org
Megan Jagosky, MD
- Recruiting
Atrium Health Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27103
Shailaja Raj, MD, 336-716-7970, Shailaja.Raj@advocatehealth.org
About this study
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.
Read the detailed description
This is a single arm, phase II, open-label study of metformin in combination with physician directed SOC first-line systemic therapy in participants with advanced unresectable or metastatic STS. Participants will continue study treatment for 5 years or until early treatment discontinuation. Metformin treatment intervention should begin no later than 4 weeks from the initiation of front-line SOC therapy.
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. 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.
Toleration of the 1000mg ER daily dose will be defined by the participant meeting all criteria below at the Course 1-Day15 (+ 7 days) study visit:
- No grade 3/4 metformin-related toxicities since initiation of metformin
- No metformin-related GI upset since initiation of metformin including diarrhea
- Acceptable organ function
- The treating provider must agree the participant has sufficiently tolerated the starting dose of the treatment intervention.
If toleration has been deemed acceptable, by meeting all criteria above as outlined, 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 above for dose escalation, the participant will continue to receive 1000mg ER daily.
- Conditions
- Sarcoma Metastatic, Sarcoma, Soft Tissue
- Being tested
- Metformin Hydrochloride ER
- Keywords
- Advanced Unresectable or Metastatic Soft Tissue Sarcoma, Metformin Hydrochloride
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin Hydrochloride ERDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Metformin Hydrochloride ER |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From date of metformin start to date of death, or censored at 12 months, whichever occurred first.
Secondary outcomes (2)
Overall survival (OS)
OS is defined as the duration of time from initiation of metformin to date of death from any cause. Surviving participants will be censored at the last known date they were alive.
Measured: From date of metformin start to date of death, or censored as described; assessed for approximately 5 years.
Cancer specific survival
Cancer specific survival is defined as the duration of time from initiation of metformin to date of sarcoma-related death. For participants who die from causes unrelated to sarcoma, cancer-specific survival will be calculated at the date of death, with non-cancer specific death as a competing risk event. Surviving participants will be censored at the last known date they were alive.
Measured: From date of metformin start to date of death, or censored as described; assessed for approximately 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2025
- Study start4 Mar 2026
- Primary completionOct 2028 (estimated)
- Study completionOct 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sarcoma MetastaticStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Arm, Metformin
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Atrium Health Levine Cancer Institute, Paula Takacs Foundation
- Responsible party
- Sponsor
- Investigators
- Megan Jagosky, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07291297
- Sponsor's protocol ID
- IRB00138078
- Other IDs
- ONC-SAR-2401
- Status last verified
- Jul 2026
- First submitted
- 17 Dec 2025
- Last updated
- 23 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin Hydrochloride in Combination With Standard of Care Systemic Therapy in Previously Untreated Advanced Unresectable or Metastatic Soft Tissue Sarcoma
- ClinicalTrials.gov ID
- NCT07291297
- Acronym / sponsor ID
- IRB00138078
- Conditions
- Sarcoma Metastatic, Sarcoma, Soft Tissue
- Keywords
- Advanced Unresectable or Metastatic Soft Tissue Sarcoma, Metformin Hydrochloride
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- Atrium Health Levine Cancer Institute, Paula Takacs Foundation
- Study start
- 4 Mar 2026 (actual)
- Primary completion
- Oct 2028 (estimated)
- Study completion
- Oct 2033 (estimated)
- First posted
- 18 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a single arm, phase II, open-label study of metformin in combination with physician directed SOC first-line systemic therapy in participants with advanced unresectable or metastatic STS. Participants will continue study treatment for 5 years or until early treatment discontinuation. Metformin treatment intervention should begin no later than 4 weeks from the initiation of front-line SOC therapy.
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. 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.
Toleration of the 1000mg ER daily dose will be defined by the participant meeting all criteria below at the Course 1-Day15 (+ 7 days) study visit:
- No grade 3/4 metformin-related toxicities since initiation of metformin
- No metformin-related GI upset since initiation of metformin including diarrhea
- Acceptable organ function
- The treating provider must agree the participant has sufficiently tolerated the starting dose of the treatment intervention.
If toleration has been deemed acceptable, by meeting all criteria above as outlined, 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 above for dose escalation, the participant will continue to receive 1000mg ER daily.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Arm, Metformin
| Arm | Type | Receives |
|---|---|---|
| Metformin Hydrochloride ER | Other | Drug: Metformin Hydrochloride ER1000mg 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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)
- Adequate performance status (PS) defined as ECOG PS = 0-2
- Adequate renal function
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin Hydrochloride ERParticipants 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. | Drug | Metformin Hydrochloride ER |
Primary outcome
Number of participants surviving at 12 months
Time frame: From date of metformin start to date of death, or censored at 12 months, whichever occurred first.
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).
2 secondary outcomes
Overall survival (OS)
Time frame: From date of metformin start to date of death, or censored as described; assessed for approximately 5 years.
Cancer specific survival
Time frame: From date of metformin start to date of death, or censored as described; assessed for approximately 5 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Megan Jagosky, MD principal investigator
Wake Forest University Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin Hydrochloride ER in people with Sarcoma Metastatic and Sarcoma, Soft Tissue, run by Wake Forest University Health Sciences at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Leah Wilson, RN (980-442-2333, Leah.J.Wilson@advocatehealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants surviving at 12 months (time frame: From date of metformin start to date of death, or censored at 12 months, whichever occurred first.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jul 2026.