Capecitabine + Elacestrant for Breast Cancer

(CAPELA Trial)

Overseen By Kristina Fanucci, MD, MHS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kristina A. Fanucci

Must be taking: GnRH agonists

Must not be taking: CYP3A inhibitors

Disqualifiers: Active brain metastases, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 25

Duration: 27 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining two drugs, capecitabine and elacestrant (a type of hormone therapy), offers better treatment for advanced estrogen receptor-positive (ER+) breast cancer. The study targets patients whose cancer no longer responds to CDK 4/6 inhibitors, such as palbociclib or ribociclib. Participants will be divided into groups to receive either capecitabine alone or both drugs to determine which is more effective. Those with ER+ breast cancer that has spread or cannot be surgically removed, and who have not benefited from CDK 4/6 inhibitors, might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does exclude participants who have taken certain therapies within 14 days before the study. It also excludes those on medications that interact with the study drugs. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that capecitabine is safe for treating breast cancer. Common side effects include diarrhea and hand-foot syndrome, which causes redness, swelling, and pain on the palms or soles. These side effects are generally manageable.

Research has shown that elacestrant is also well-tolerated. The most common side effects are nausea and tiredness, which are usually mild and manageable.

When used together, capecitabine and elacestrant show safety data similar to each drug on its own. Most side effects, like nausea and tiredness, are manageable and resemble those experienced with each drug individually.

Overall, both drugs have been used safely in other treatments. This study aims to explore their combined effect, but existing research suggests they are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Capecitabine and Elacestrant for breast cancer treatment because together they offer a potentially more effective approach than current options. Capecitabine is already known for its ability to disrupt cancer cell DNA, but combining it with Elacestrant, which targets estrogen receptors, could enhance the treatment's effectiveness, especially in patients with specific genetic mutations like ESR1. This dual approach may provide a targeted treatment for those with hormone receptor-positive breast cancer, particularly when standard endocrine therapies fall short. Additionally, the option to switch to Elacestrant monotherapy upon progression offers flexibility and a personalized treatment pathway, which could lead to improved outcomes for patients.

What evidence suggests that this trial's treatments could be effective for advanced ER+ breast cancer?

In this trial, participants will be randomized to receive either the combination of capecitabine and elacestrant or capecitabine alone. Studies have shown that the combination of capecitabine and elacestrant holds promise for treating advanced estrogen receptor-positive (ER+) breast cancer. Research indicates that elacestrant can double the time patients live without cancer progression compared to some other treatments, with 6-month rates at 41% versus 19%. Capecitabine, a chemotherapy drug, is already known for its effectiveness in breast cancer. When used together, these drugs might work better, as similar combinations have demonstrated a synergistic effect, meaning they work better together than alone. Elacestrant alone has also proven effective, with real-world data showing patients live without cancer worsening for 5 to 7 months. These findings suggest the combination could be a strong option for those who have not responded to other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

Kristina Fanucci, MD, MHS

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for individuals with advanced estrogen receptor-positive (ER+) breast cancer that no longer responds to CDK 4/6 inhibitors like palbociclib. Participants must have previously been treated with these medications.

Inclusion Criteria

Ability to understand and sign a written informed consent document

HCV-infected participants eligible if HCV viral load undetectable

Participants must agree to use adequate contraception if of childbearing age, postmenopausal through use of GNRH agonists, or male

Exclusion Criteria

Participants receiving concurrent therapy with other investigational agents

I haven't taken strong CYP3A inhibitors in the last 2 weeks.

I haven't had hormone or biological therapy in the last 14 days or I'm still experiencing side effects from previous treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either Capecitabine alone or Capecitabine with Elacestrant in 21-day cycles

27 weeks

Imaging every 9 weeks, in-clinic visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6 months after end of treatment

Follow-up visits every 6 months

Optional Extension

Participants in Arm B with ESR1 mutation may switch to Elacestrant monotherapy after progression

Until progression

Imaging every 9 weeks, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• Elacestrant

Trial Overview The study compares the effectiveness of combining two drugs, capecitabine and elacestrant, against using capecitabine alone in treating ER+ breast cancer that's resistant to certain therapies.

How Is the Trial Designed?

Group I: Optional switch after progression on Arm B Capecitabine monotherapy: Elacestrant Monotherapy Experimental Treatment 1 Intervention

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

Group II: Arm B: Capecitabine Monotherapy Experimental Treatment 1 Intervention

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

Group III: Arm A: Capecitabine + Elacestrant Experimental Treatment 2 Interventions

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

Who Is Running the Clinical Trial?

Kristina A. Fanucci

Lead Sponsor

Stemline Therapeutics, Inc.

Industry Sponsor

Trials

24

Recruited

6,500+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Menarini Group

Industry Sponsor

Trials

45

Recruited

12,600+

Translational Breast Cancer Research Consortium

Collaborator

Trials

27

Recruited

3,100+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07222215

PhII Randomized CAPecitabine + ELAcestrant vs. ... The goal of this research study is to compare a combination of two drugs, capecitabine and elacestrant to capecitabine alone as a treatment ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11162492/

Pure estrogen receptor antagonists potentiate capecitabine ... Results. Fulvestrant combined with chemotherapy has additive to synergistic activity in ER+ breast cancer cells. To investigate the impact of ...

3. withpower.com withpower.com/trial/phase-2-esr1-gene-mutation-11-2025-4d8b6

Capecitabine + Elacestrant for Breast Cancer (CAPELA Trial) The goal of this research study is to compare a combination of two drugs, capecitabine and elacestrant to capecitabine alone as a treatment ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01836-2/pdf

369P Elacestrant combinations in patients (pts) with ... The phase Ib study. (NCT04851613) showed that the combination of afuresertib plus fulvestrant has prom- ising efficacy in subjects with HR+/HER2- LA/mBC who ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)01470-4/fulltext

Elacestrant in ESR1-mutant, endocrine-responsive ... Accordingly, the landmark analysis showed 6- and 12-month PFS rates were doubled in the elacestrant arm (6 months: 41% versus 19%; 12 months: 27 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4770778/

Efficacy and safety of capecitabine-based first-line ... Capecitabine-based chemotherapy significantly improves ORR and PFS in patients with advanced breast cancer, but has no demonstrable impact on OS.

7. esmoopen.com esmoopen.com/article/S2059-7029(25)01437-1/fulltext

Adjuvant capecitabine in patients with triple-negative ... Compared with patients with RD, survival rates among patients who experienced pCR were higher at each landmark, with 89.3% of patients being ...

8. ascopubs.org ascopubs.org/doi/10.1200/OA-24-00068

Randomized Trial of Fixed-Dose Capecitabine Compared ... In MBC, FD capecitabine 1,500 mg twice daily on a 7/7 schedule has less toxicity and similar efficacy when compared with body surface area-based ...

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa1612645

Adjuvant Capecitabine for Breast Cancer after ... The addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative ...

10. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.899423/full

Efficacy and Safety of Capecitabine for Triple-Negative ... From the available data of TNBCs, the capecitabine group demonstrated significantly higher rates of diarrhea (OR = 3.10, 95% CI 2.32–4.15), hand ...