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

Recruiting now · Phase 2

Conditions studied: Estrogen-receptor-positive Breast Cancer, Metastatic Breast Cancer, Breast Cancer, Hormone Receptor Positive Breast Cancer, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, HER2- Breast Cancer, ESR1 Gene Mutation, ER Wildtype, Breast Neoplasms

In brief

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)

Key facts

Study ID

NCT07222215

Run by

Kristina A. Fanucci

People needed

297

Starts

2026-01-16

Expected to finish

2030-10-01

Last updated by the study team

2026-06-12

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 <18 years of age are excluded from this study
• Women must be postmenopausal, which is defined as any of the following:
• Age ≥ 60 years
• Age < 60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range
• Premenopausal women who have been on a GnRH agonist for at least three consecutive months prior to study entry are eligible. Women in this group MUST remain on the GnRH agonist for the duration of protocol treatment.
• Status-post bilateral oophorectomy or total hysterectomy after adequate healing post-surgery
• Must have measurable or evaluable disease by RECIST 1.1. Must have progressed on at least one line of endocrine therapy in the metastatic setting or recurred on or within one year of adjuvant endocrine therapy
• Unrestricted number of prior endocrine therapies (with or without targeted treatment) are allowed in the advanced disease setting. If a patient recurred on or within one year of adjuvant endocrine therapy, it would be counted as one line of treatment.
• Prior CDK4/6 inhibition is required (in adjuvant or metastatic disease), unless a CDK4/6 inhibitor is contraindicated (CDK4/6 inhibitor in combination with endocrine treatment is considered as one line of endocrine treatment).
• Participants must have remained on a prior endocrine treatment alone or in combination with a CDK4/6 inhibitor in the metastatic setting without progression for at least 6 months prior to study entry. This regimen does not need to be the most recent regimen prior to study entry. If patients have progressed on adjuvant endocrine treatment and have not received treatment in the metastatic setting, they must have progressed after at least two years of adjuvant endocrine treatments.
• Prior alpelisib with endocrine treatment is allowed (considered as a line of endocrine treatment).
• Prior everolimus with endocrine treatment is allowed (considered a line of endocrine treatment).
• Prior capivasertib with endocrine treatment is allowed (considered a line of endocrine treatment)
• Prior fulvestrant is permitted. Prior SERM (tamoxifen, lasofoxifene) is permitted. Neither prior oral SERDs nor other next generation oral endocrine therapies (such as PROTACS) are permitted.
• No prior chemotherapy regimen or ADC is allowed in the metastatic setting.
• Participants may have received radiotherapy for palliative purposes but must not be experiencing grade >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

You may not qualify if…

• 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 <1cm. Patients with leptomeningeal disease are not eligible. It is unlikely that these patients will benefit from this regimen.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, clinically significant cardiovascular disease including: cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, uncontrolled diabetes mellitus, gastrointestinal disorders potentially affecting the absorption of elacestrant, inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or total gastric resection, or psychiatric illness/social situations that would limit compliance with study requirements. Active hepatitis B or active hepatitis C infection. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation. This could increase risk of toxicity from treatment and potentially decrease adherence to study protocol.
• Individuals with a history of a different malignancy are ineligible except for the following circumstances:
• (1) Individuals with a history of other malignancies are eligible if they have been disease-free for at least 3 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. These cases should be discussed with the sponsor-investigator prior to enrollment.
• (2) Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin. History of prior malignancy puts patients at risk of recurrence from their prior malignancy or progression of a second malignancy which would complicate interpretation of the end points of this trial.
• Ongoing treatment with drugs that are sensitive substrates of P-glycoprotein (dabigatran, digoxin, fexofenadine) or BRCP (rosuvastatin, sulfasalazine). These drugs have potential drug-drug interactions with the study agents.
• Treatment with strong CYP3A inhibitors within 2 weeks before first study treatment administration or five elimination half-lives, whichever is longest and cannot be replaced.
• Medical conditions requiring concomitant administration of medications with a narrow therapeutic window metabolized by CYP3A and for which a dose reduction cannot be considered. See Appendix D for a list of medications that are CYP3A substrates. These drugs have potential drug-drug interactions with the study agents.
• Female participants lactating or nursing. The safety of these medications in pregnancy or breast feeding patients is unknown.
• Both men and women of all races and ethnic groups are eligible for this trial.

Where it is running

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.