Study of Zunsemetinib with Capecitabine for Metastatic Breast Cancer
This study is looking at a new combination treatment for people with hormone receptor-positive, HER2-negative metastatic breast cancer that has spread to the bones. It combines zunsemetinib with capecitabine, along with standard bone-strengthening medicines like zoledronic acid or denosumab. The study aims to see how safe this combination is and how well it works. You might be able to join if you have this type of breast cancer, are at least 18 years old, and your doctor thinks capecitabine is a good treatment option for you. The study will measure side effects and help determine the best dose of zunsemetinib.
- Study design
- This is a Phase Ib/II study, meaning it's in early stages to test safety and effectiveness. It plans to enroll 152 participants.
- What's involved
- You would take zunsemetinib and capecitabine daily at specific times. You would also receive zoledronic acid or denosumab as part of your standard care.
- Compensation
- Not stated in the trial record.
- Follow-up
- Side effects will be monitored for up to 30 days after your last treatment, which is estimated to be 11 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06374459
Zunsemetinib in Combination With Capecitabine in Patients With Hormone Receptor-Positive and HER2-Negative Metastatic Breast Cancer With Bone Metastasis
Recruiting
PHASE1Ages 18+InterventionalTreatmentWashington University School of MedicineInvestigator-initiated
~152 participants
Updated 2026-04-20 on ClinicalTrials.gov
What's tested:ZumsemetinibCapecitabineZoledronic acidDenosumab
At a glance
Recruiting sites
2 of 3 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Number of participants with adverse events (Phase Ib only)
Measured over From start of treatment through 30 days after end of treatment (estimated to be 11 months)
+4 more outcomes measured
Conditions
Where it's being run
3 sites across 3 statesKansas1
Minnesota1
Missouri1
Study leadership
- Cynthia X Ma, M.D., Ph.D. · PRINCIPAL_INVESTIGATOR · Washington University School of Medicine
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Hormone receptor-positive, HER2-negative metastatic breast cancer.
Measurable or non-measurable but evaluable disease by RECIST v1.1.
Candidate for capecitabine treatment per physician decision. See below phase-specific eligibility criteria for further guidance.
No more than one prior chemotherapy for metastatic disease.
Patient must have received prior endocrine therapy with CDK4/6 inhibitor.
If patient is on denosumab or zoledronic acid prior to enrollment, patient must have been on the regimen for at least 6 months prior to study. However, a washout of 3 weeks is required prior to C1D1.
At least 18 years of age.
ECOG performance status 0, 1, or 2
Life expectancy of at least 12 weeks.
Adequate bone marrow and organ function as defined below:
Leukocytes ≥ 3 K/cumm
Absolute neutrophil count (ANC) ≥ 1.5 K/cumm
Platelets ≥ 100 K/cumm
Total bilirubin ≤ 1.5 x IULN (or total bilirubin ≤ 3 mg/dL if patient has known Gilbert Syndrome)
AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
Creatinine clearance \> 60 mL/min by Cockcroft-Gault
Calcium within normal limits
Women of childbearing potential and men who are heterosexually active must agree to use adequate contraception as specified in the protocol. Contraception should continue for 6 months (for women) or 3 months (for men) after the end of treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
Ability to understand and willingness to sign an IRB approved written informed consent document.
Patients must have archival tissue sample available from prior metastatic biopsy. If no tissue is available, patient may still be able to enroll with PI approval.
Presence of bone metastasis is not required.
Candidate for, or currently on stable doses of capecitabine, defined as capecitabine: 1000 mg/m\^2 BID, 14 days on and 7 days off. A stable dose of capecitabine is defined as no more than grade 1 AEs related to capecitabine on the 1000 mg/m\^2 BID, 14 days on and 7 days off dose for at least 1 cycle. Capecitabine is not counted as a prior chemotherapy regimen in these patients.
Progressive bone metastasis per the most recent tumor imaging studies by RECIST 1.1 or clinical progression (such as worsening bone pain, elevation of tumor marker) per treating physician.
Exclusion
Patients may not have received the following investigational or SOC therapies within the below specified time frames prior to C1D1:
Radiation therapy within 1 week
Systemic chemotherapy, including antibody drug conjugates with chemotherapy payload, within 3 weeks.
Immunotherapy within 3 weeks
Oral chemotherapy or molecularly targeted therapy within 5 half-lives of the agent.
Endocrine therapies do not have a required washout and may be continued until C1D1.
Strong and moderate CYP3A4 and CYP2C8 inhibitors (including grapefruit), strong and moderate CYP3A and CYP2C8 inducers, and drugs with QT prolonging potential within 5 half-lives of the agent.
Untreated brain metastases. Patients with treated brain metastases are eligible if they show no evidence of progression and are off steroids.
A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zunsemetinib or other agents used in the study.
History of acute, untreated skeletal related events (SRE) or active untreated SRE or a change or an anticipated change in the SOC anti-resorptive agents after entering the study.
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of C1D1.
Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL or they have a history of AIDS-defining opportunistic infection within the 12 months prior to Cycle 1 Day 1. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.
Screening resting QTcF above 470 msec.
Capecitabine within 2 weeks prior to C1D1. Patients may be currently taking capecitabine, but must not have dosed within 2 weeks prior to C1D1 for study correlative purposes.
Prior capecitabine in the metastatic setting.
History of other malignancy, unless all treatment was completed and patient had no evidence of disease within 2 years of C1D1.
What this trial measures
- Number of participants with adverse events (Phase Ib only)From start of treatment through 30 days after end of treatment (estimated to be 11 months)
- Recommended phase II dose of zunsemetinib (Phase Ib only)Through end of 1st cycle (each cycle is 21 days)
- Number of participants with dose-limiting toxicities (Phase Ib only)Through end of 1st cycle (each cycle is 21 days)
- Percent change in serum CTX (Phase II only)Baseline and Day 1 of week 7
- Progression-free survival (PFS) (Phase II only)From start of treatment through completion of follow-up (estimated to be 3 years and 10 months)