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

NCT07222215 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-605
• Study Type: interventional
• Target: 297
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

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; Estrogen-receptor-positive Breast Cancer

Keywords

Advanced Estrogen Receptor-Positive Breast Cancer; Metastatic Breast Cancer; Breast cancer; Hormone receptor positive breast cancer; Advanced Human Epidermal Growth Factor Receptor 2 negative breast cancer; HER2- Breast Cancer; ESR1 gene mutation; ER wildtype

Outcome Measures

Primary Outcomes (2)

• Progression Free Survival (PFS) in ESR1 mutant population

  PFS based on the Kaplan-Meier method is defined as the time from study randomization to disease progression per RECIST 1.1 or death. Patients alive without disease progression are censored at the date of last disease evaluation.

  Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles.

• Progression Free Survival (PFS) in intention to treat (ITT) population

  PFS based on the Kaplan-Meier method is defined as the time from study randomization to disease progression per RECIST 1.1 or death. Patients alive without disease progression are censored at the date of last disease evaluation.

  Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles.

Secondary Outcomes (10)

• Overall Survival (OS) in ESR1 mutant population

  Follow up or other contact every 2 months for 24 months until time of second progression, then every 6 months for 5 years

• Objective Response Rate in ESR1 mutant population

  Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles

• Clinical benefit rate (CBR) in ESR1 mutant population

  Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles

• Second progression event (PFS2) in ESR1 mutant population

  Follow up or other contact every 2 months for a total of 24 months or until progressive disease

• Overall survival (OS) in ITT population

  Follow up or other contact every 2 months for 24 months until time of second progression, then every 6 months for 5 years

Other Outcomes (3)

• Overall survival (OS) ESR1 mutation not detected population

  Follow up or other contact every 2 months for 24 months until time of second progression, then every 6 months for 5 years

• Progression-free survival rate (PFS)

  Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles

• Second progression event (PFS2)

  Follow up or other contact every 2 months for a total of 24 months or until progressive disease

Study Arms (3)

Arm A: Capecitabine + Elacestrant

EXPERIMENTAL

Participants will be randomized 1:1, enrolled, and stratified based on the receipt of one or two prior lines of endocrine therapy in the metastatic setting, presence or absence of visceral disease, presence or absence of ESR1 mutation, and presence or absence of p53 mutation. * Baseline visit with assessments * Imaging every 9 weeks for 27 weeks, then every 12 weeks * Cycle 1 through End of Treatment (21-day cycles): * Days 1 - 14: Predetermined dose of Capecitabine 2x daily for 14 days followed by 7 days off * Days 1 - 21: Predetermined dose of Elacestrant 1x daily * Follow up: every 6 months after end of treatment

Drug: Capecitabine; Drug: Elacestrant

Arm B: Capecitabine Monotherapy

EXPERIMENTAL

Participants will be randomized 1:1, enrolled, and stratified based on the receipt of one or two prior lines of endocrine therapy in the metastatic setting, presence or absence of visceral disease, presence or absence of ESR1 mutation, and presence or absence of p53 mutation. * Baseline visit with assessments * Imaging every 9 weeks for 27 weeks, then every 12 weeks * Cycle 1 through End of Treatment (21-day cycles): --Days 1 - 14: Predetermined dose of Capecitabine 2x daily for 14 days followed by 7 days off * Follow up: every 6 months after end of treatment

Drug: Capecitabine

Optional switch after progression on Arm B Capecitabine monotherapy: Elacestrant Monotherapy

EXPERIMENTAL

For Arm B participants with ESR1 mutation, at the time of progression on Capecitabine participants have the option to continue on trial and switch to single agent Elacestrant monotherapy. -Imaging every 9 weeks for 27 weeks, then every 12 weeks Through End of Treatment (21-day cycles): --Days 1 - 21: Predetermined dose of Elacestrant 1x daily -Follow up: every 6 months after end of treatment

Drug: Elacestrant

Interventions

Capecitabine DRUG

A fluoropyrimidine carbamate, tablet taken orally, per standard of care.

Also known as: Xeloda

Arm A: Capecitabine + Elacestrant; Arm B: Capecitabine Monotherapy

Elacestrant DRUG

A selective estrogen receptor degrader, tablet taken orally, per standard of care

Also known as: RAD1901, Elacestrant Dihydrochloride, RAD1901 - 2 HCl, C30H40Cl2N2O2

Arm A: Capecitabine + Elacestrant; Optional switch after progression on Arm B Capecitabine monotherapy: Elacestrant Monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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 testing documenting ESR1 mutation status. In patients without ESR1 mutation, this result must be from within 2 months.
• qualifying ESR1 mutations: E380Q, V422del, S436P, L536H, L536P, L536R, Y537C, Y537D, Y537N, Y537S, D538G
• 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
• Up to two 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).

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. (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.

Sponsors & Collaborators

• Johns Hopkins University: collaborator
• Translational Breast Cancer Research Consortium: collaborator
• Menarini Group: collaborator
• Kristina A. Fanucci: lead
• Stemline Therapeutics, Inc.: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine; elacestrant; RAD1901

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Kristina Fanucci, MD, MHS

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristina Fanucci, MD, MHS

CONTACT

617-632-3800; Kristina_Fanucci@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 23, 2025
• First Posted: October 29, 2025
• Study Start: January 16, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

US (1)