174 Participants Needed

Elacestrant vs Elacestrant + CDK4/6 Inhibitor for Breast Cancer

SC
Overseen ByStudy Coordinator
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Northwestern University
Must be taking: CDK4/6 inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating estrogen receptor-positive (ER+) and HER2-negative breast cancer. Researchers aim to determine if the drug elacestrant is more effective alone or when combined with a CDK4/6 inhibitor, such as abemaciclib, palbociclib, or ribociclib. It targets individuals who have previously tried other treatments, including a CDK4/6 inhibitor, for their metastatic breast cancer, which has spread to other parts of the body. Participants must have this specific type of breast cancer and have undergone at least two prior endocrine therapies. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop all current medications, but there is a 14-day washout period required if you were previously on a CDK4/6 inhibitor before starting a different one in the study. Additionally, you cannot take strong or moderate CYP3A4 inducers or inhibitors.

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

A previous study found that elacestrant caused common side effects such as nausea, tiredness, vomiting, and diarrhea. These side effects are expected. When combined with CDK4/6 inhibitors like palbociclib, abemaciclib, or ribociclib, the side effects were similar to those seen with these drugs alone, with no additional side effects.

Research also shows that most people can handle the combination of elacestrant with these inhibitors without unexpected or severe reactions, indicating that the treatment is generally well-tolerated. These findings from earlier studies help predict current reactions to the treatment. For those considering joining a trial, these results suggest a manageable safety profile based on previous research.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they offer new ways to tackle the disease. Elacestrant is a selective estrogen receptor degrader (SERD), which works differently from standard hormone therapies by directly targeting and breaking down estrogen receptors, potentially offering more effective control over cancer growth. The combination therapy adds a CDK4/6 inhibitor, like Palbociclib, Abemaciclib, or Ribociclib, which interfere with cancer cell division, aiming to enhance the effects of Elacestrant. This dual approach could offer a powerful option, especially for patients who may not respond to current hormone therapies.

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

Research shows that elacestrant may effectively treat hormone receptor-positive metastatic breast cancer. In real-world studies, patients taking elacestrant experienced stable cancer for about 5 to 7 months. This trial will provide participants with either elacestrant alone or in combination with CDK4/6 inhibitors such as palbociclib, abemaciclib, or ribociclib. When combined with these inhibitors, elacestrant is generally well-tolerated and may yield better results. Early findings suggest that this combination might be more effective, especially for patients who have already tried other treatments. Overall, using elacestrant alone or with CDK4/6 inhibitors appears promising for treating this type of breast cancer.678910

Who Is on the Research Team?

William J. Gradishar, MD | Northwestern ...

William Gradishar, M.D.

Principal Investigator

Northwestern University

Are You a Good Fit for This Trial?

This trial is for adults with ER+/HER2- advanced or metastatic breast cancer who have tried at least two endocrine therapies, including a CDK4/6 inhibitor. They should be in good physical condition (ECOG 0 or 1), have no severe heart issues, and not be at immediate risk due to visceral spread. Participants must not have had recent chemotherapy, major surgery, or certain other treatments.

Inclusion Criteria

My cancer has a confirmed ESR1 mutation.
I have at least one tumor that can be measured or a mainly lytic bone lesion.
I have had at least 2 hormone treatments for my cancer, including a CDK4/6 inhibitor.
See 10 more

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 28 days.
I do not have any uncontrolled illnesses.
My advanced cancer is causing symptoms and could lead to serious complications soon.
See 10 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either elacestrant monotherapy or combination therapy with a CDK4/6 inhibitor for each 28-day cycle until progressive disease or other criteria are met

Variable (until progression or other criteria)
Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for survival and disease progression every 36 weeks for 2 years, then every 72 weeks up to 5 years

Up to 5 years
Every 36 weeks for 2 years, then every 72 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Abemaciclib
  • Elacestrant
  • Palbociclib
  • Ribociclib
Trial Overview The study tests if elacestrant's effectiveness improves when combined with a CDK4/6 inhibitor (palbociclib, abemaciclib, ribociclib) in patients previously treated with a CDK4/6 inhibitor. It aims to overcome resistance often seen in this common subtype of breast cancer after standard treatment.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: Elacestrant MonotherapyExperimental Treatment1 Intervention
Group II: Combination TherapyExperimental Treatment1 Intervention

Elacestrant is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as Orserdu for:
🇪🇺
Approved in European Union as Orserdu for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

Northwestern University

Lead Sponsor

Trials
1,674
Recruited
989,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have shown positive results in clinical trials for treating estrogen receptor positive (ER+)/HER2-negative metastatic breast cancer, indicating a shift in treatment strategies.
These inhibitors work by targeting key kinases that promote cancer cell proliferation, leading to improved outcomes and potentially better quality of life for patients compared to traditional sequential endocrine therapy.
Clinical development of CDK4/6 inhibitor for breast cancer.Iwata, H.[2019]
CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have significantly improved treatment outcomes for hormone receptor-positive and HER2-negative breast cancer, establishing themselves as key options in both first- and second-line therapies.
While these inhibitors effectively prolong overall survival and progression-free survival in patients, they are also associated with notable adverse events, highlighting the need for careful monitoring during treatment.
An Overview of the Safety Profile and Clinical Impact of CDK4/6 Inhibitors in Breast Cancer-A Systematic Review of Randomized Phase II and III Clinical Trials.Stanciu, IM., Parosanu, AI., Nitipir, C.[2023]
Elacestrant is the first oral selective estrogen receptor degrader (SERD) approved by the FDA for treating ER/PR-positive, HER2-negative metastatic breast cancer with ESR1 mutations, showing improved median progression-free survival compared to standard endocrine therapy in the EMERALD trial.
The drug acts as a mixed ER agonist/antagonist and has specific metabolic considerations, being primarily processed by CYP3A4, which can lead to drug interactions; dose adjustments are recommended for patients with moderate hepatic dysfunction.
Pharmacology and pharmacokinetics of elacestrant.Beumer, JH., Foldi, J.[2023]

Citations

Elacestrant in hormone receptor-positive metastatic breast ...Elacestrant shows promise for improving outcomes in hormone receptor-positive metastatic breast cancer, but further research is needed to confirm its ...
Real-World Data Reveal Longer PFS With Elacestrant in ...Wander acknowledges the lack of uniform scans, but despite these limitations, elacestrant performed well, with PFS estimates of 5 to 7 months.
Real-world (RW) elacestrant use patterns and therapeutic ...In the EMERALD study, pts with ESR1-mutant (ESR1m) HR+/HER2-negative aBC had a median progression free survival (PFS) of 3.8 months (mos). Here, ...
4.orserduhcp.comorserduhcp.com/efficacy/
EMERALD Trial Primary Endpoint & Efficacy - orserduORSERDU (elacestrant) is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor ...
Elacestrant in ESR1-mutant, endocrine-responsive ...Compared with the control arm, elacestrant therapy was associated with more grade 1-2 toxicity, including nausea (35% versus 19%) and vomiting ( ...
Post-marketing safety of elacestrant in breast cancerFDA data analysis revealed that the most commonly reported elacestrant-related AEs were nausea, fatigue, disease progression, vomiting, diarrhea ...
Elacestrant combinations in patients (pts) with ER+/HER2- ...Elacestrant combinations continue to demonstrate safety consistent with the known profiles of each drug + SOC ET without increased risk of associated AEs.
Elacestrant Combinations in ER+/HER2- Locally ... - OncLivePresented by Dr. Hope S. Rugo, this slide deck presents updated phase 1b/2 safety and efficacy results from the ELEVATE trial of elacestrant ...
Evaluation of Safety of Elacestrant in Patients with Breast ...This study offers real-world insights into elacestrant usage, confirming known adverse reactions and identifying previously unreported events.
Metastatic Breast Cancer (mBC) at the ASCO 2025 Annual ...Preliminary efficacy analysis from the elacestrant plus everolimus and ribociclib cohorts of the ELEVATE study, along with updated safety data ...
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