Adaptive capecitabine therapy for metastatic ER-positive, HER2-negative breast cancer
Single Arm Pilot Trial of Adaptive Therapy (AT) With Capecitabine for the Treatment of Metastatic Estrogen Receptor Positive, Hormone Refractory Breast Cancer
This trial will try using capecitabine with dose changes based on tumor imaging and blood markers in adults with metastatic ER-positive, HER2-negative breast cancer.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 35 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | Denosumab, chemotherapy, Radiation |
| Locations | 1 site (Scottsdale, Arizona) |
| Trial ID | NCT06525766 on ClinicalTrials.gov |
What this trial studies
This Phase II trial uses an adaptive therapy approach where capecitabine dosing is changed cycle-to-cycle based on tumor burden measured by imaging and tumor markers. Patients with measurable metastatic ER-positive, HER2-negative breast cancer receive capecitabine and undergo scheduled imaging, 3D volumetric lesion measurements, and blood sampling for circulating tumor DNA. The study measures feasibility of making adaptive dose modifications, time to progression, overall survival, quality of life, and treatment-related adverse events. Exploratory objectives include using ctDNA as a lower-cost tumor burden measure and sequencing to identify genomic predictors of response or resistance.
Who should consider this trial
Good fit: Adults (≥18 years) with histologically confirmed ER-positive, HER2-negative metastatic breast cancer with measurable disease, ECOG 0–2, and adequate blood counts and liver function are ideal candidates.
Not a fit: Patients with HER2-positive or rapidly progressive disease, significant organ dysfunction, or who cannot take oral capecitabine are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could slow disease growth while reducing unnecessary drug exposure and toxicity by tailoring capecitabine dosing to each patient’s tumor burden.
How similar studies have performed: Capecitabine is an established active drug in metastatic breast cancer, but using adaptive dosing based on imaging and ctDNA is a relatively novel approach with limited prior clinical evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 18 years * Histological confirmation of estrogen-receptor positive (ER+), HER2-negative overexpression or amplification negative as per American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines, metastatic breast cancer * Measurable disease. Bone only disease allowed if associated with soft tissue component that is measurable by Response Evaluation Criteria is Solid Tumors (RECIST) 1.1 criteria * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2 * Hemoglobin ≥ 9.0 g/dL (obtained ≤ 14 days prior to registration), no transfusions allowed ≤ 14 days prior to registration * Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (obtained ≤ 14 days prior to registration) * Platelet count ≥ 100,000/mm\^3 (obtained ≤ 14 days prior to registration) * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (obtained ≤ 14 days prior to registration) * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) (obtained ≤ 14 days prior to registration) * Prothrombin time (PT)/international normalized ratio (INR)/activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy (obtained ≤ 14 days prior to registration) * Calculated creatinine clearance ≥ 45 ml/min using the Cockcroft-Gault formula (obtained ≤ 14 days prior to registration) * Negative serum or urine pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Provide written informed consent * Ability to complete questionnaire(s) by themselves or with assistance * Willingness to provide mandatory blood specimens for correlative research * Ability to undergo re-staging CT scans as required by the protocol * Willing to return to enrolling institution at the specified frequency for follow-up (during the active monitoring phase of the study) Exclusion Criteria: * Prior chemotherapy or use of antibody drug conjugate in the metastatic setting * Any of the following, because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects: * Pregnant persons * Nursing persons * Persons of childbearing potential who are unwilling to employ adequate contraception * Any of the following prior therapies: * Major surgery ≤ 3 weeks prior to registration * Radiation therapy ≤ 2 weeks prior to registration * Evidence of visceral crisis or impending cord compression * Evidence of uncontrolled brain metastasis requiring whole brain irradiation or intervention * Uncontrolled intercurrent illness including, but not limited to: * ongoing or active infection * symptomatic congestive heart failure * unstable angina pectoris * uncontrolled cardiac arrhythmia * chronic oxygen dependence * respiratory failure * or psychiatric illness/social situations that would limit compliance with study requirements * Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm * Other active malignancy ≤ 3 years prior to registration. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix * If there is a history of prior malignancy, they must not be receiving other cancer specific treatment. Except for antiestrogen treatment (aromatase inhibitors or selective estrogen modulators) for their cancer are permitted if they meet other eligibility criteria. Denosumab and zoledronic acid, are permitted as established adjunct therapies per guidelines * History of myocardial infarction ≤ 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias * Patients known to have certain homozygous or compound heterozygous dihydropyrimidine dehydrogenase (DPYD) variants that result in complete absence of deoxypyridinoline (DPD) activity * History of severe hypersensitivity reactions to fluorouracil or capecitabine
Where this trial is running
Scottsdale, Arizona
- Mayo Clinic in Arizona — Scottsdale, Arizona, United States (Recruiting)
Study contacts
- Principal investigator: Lida A. Mina, M.D. — Mayo Clinic
- Study coordinator: Clinical Trials Referral Office
- Email: mayocliniccancerstudies@mayo.edu
- Phone: 855-776-0015
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.