PhII Randomized CAPecitabine + ELAcestrant vs. Capecitabine Alone in ER+ Breast Cancer (CAPELA)

The goal of this research study is to compare a combination of two drugs, capecitabine and elacestrant to capecitabine alone as a treatment for advanced estrogen receptor-positive (ER+) breast cancer. This study is designed for participants with cancer that has previously stopped responding to medication in the class of therapy called CDK 4/6 inhibitors, including palbociclib, ribociclib, or abemaciclb. The names of the study drugs involved in this study are: * Elacestrant (a type of selective estrogen receptor degrader) * Capecitabine (a type of fluoropyrimidine antimetabolite)

Inclusion Criteria: * Participants must have histologically confirmed estrogen receptor-positive (ER+), HER2-negative metastatic or locally recurrent unresectable (advanced) invasive breast cancer. ER and HER2 measurements should be performed according to institutional guidelines in a CLIA-approved setting. ER must be ≥ 10% on the most recent biopsy in which receptor testing was performed. Cutoff values for positive/negative HER2 staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines. * Participants must have standard of care ctDNA sequencing testing documenting ESR1 and TP53 mutation status. In patients without ESR1 mutation, this result must be from within 3 months. * ESR1 mutations that are considered pathogenic are: E380Q, V422del, S436P, L536H, L536P, L536R, Y537C, Y537D, Y537N, Y537S, D538G * TP53 mutations that are considered pathogenic as determined by a CLIA certified laboratory * Women or men age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of capecitabine in combination with elacestrant participants \1 treatment-related toxicities at study entry and must have completed treatment \> 14 days prior to registration. * ECOG PS 0-1 * Adequate hematological, liver, and kidney function, as defined below: * Absolute neutrophil count \> 1,500/µL * Platelets \> 100,000/µL * Hemoglobin \> 9 g/dL (transfusion is allowed to meet this criterion) Total bilirubin \< 1.5 x institutional upper limit or normal (ULN) or \< 3 institutional ULN in the presence of documented Gilbert's syndrome * AST (SGOT)/ALT (SGPT) \< 2.5 x institutional ULN, or ≤ 5 institutional ULN for subjects with documented metastatic disease to the liver * Creatinine clearance \> 50 mL/min/1.73 m2 * Women of childbearing age, women who are made postmenopausal through use of GNRH agonists, and men must agree to use adequate contraception for the duration of protocol treatment and for at least 6 months after the last dose of capecitabine. * Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy testing does not need to be pursued in female participants who are: * Age \> 60 years; or * Age \< 60 with intact uterus and amenorrhea for 12 consecutive months or more AND estrogen (estradiol) and FSH levels are within postmenopausal range; or * Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation * Participants must be able to swallow and retain oral medication. * Ability to understand and the willingness to sign a written informed consent document. * HIV-infected participants must have well-controlled HIV on ART, defined as: 1. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of screening. 2. Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least 12 weeks before screening. 3. It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months. 4. Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study. The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates. Note: No HIV testing is required at screening unless mandated by local health Authority. * Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before allocation. Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention.Hepatitis B screening tests are not required unless: * Known history of HBV infection * As mandated by local health authority Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening. Note: Participants must have completed curative antiviral therapy at least 4 weeks before allocation. Hepatitis C screening tests are not required unless: * Known history of HCV infection * As mandated by local health authority Exclusion Criteria: * Participants who have had endocrine and/or biologic therapy \< 14 days prior to entering the study or those who have not recovered from any prior treatment-related toxicities (must recover to no more than grade 1; alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 toxicity not constituting a safety risk based on investigator's judgment are acceptable). This is to minimize risk of drug-drug interactions and clarify etiology of future toxicities. * Participants who are receiving concurrent therapy with other investigational agents. This is to minimize risk of drug-drug interactions and clarify etiology of future toxicities. * Rapidly progressive, symptomatic, visceral spread of disease placing participant at risk of life- threatening complications in the short term. It is likely that these patients will not benefit from this regimen. * History of dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with this deficiency are prone to significant toxicity from capecitabine. * Participants with active brain metastases. Treated brain metastases that are asymptomatic and do not require systemic steroids for management of symptoms are allowed if they have received SRS (7-day washout) or WBRT (14-day washout) or asymptomatic untreated brain metastases measuring \