Elacestrant for Breast Cancer

Overseen By Stephanie Ladd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: Endocrine therapy, SERDs

Disqualifiers: Metastatic disease, Invasive cancer, others

Stay on Your Current Meds You can continue your current medications while participating

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: 7

Duration: 12 months

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that participants must have stopped endocrine therapy at least six months before screening. Other current medications are not specified in the protocol.

What data supports the effectiveness of the drug Elacestrant for breast cancer?

Research shows that Elacestrant helps patients with advanced breast cancer live longer without the disease getting worse compared to standard treatments. It was approved by the FDA based on a study that showed it worked better for certain patients with specific genetic changes in their cancer. ^{1 2 3 4 5}

Is Elacestrant safe for humans?

Elacestrant has been generally well tolerated in clinical trials, with the main side effects being upper gastrointestinal symptoms like nausea and vomiting. It has been approved by the FDA for certain types of breast cancer, indicating it has passed safety evaluations for those conditions. ^{1 6 7 8 9}

How is the drug elacestrant different from other treatments for breast cancer?

Elacestrant is unique because it is the first oral selective estrogen receptor degrader (SERD) approved for use in patients with ER-positive, HER2-negative metastatic breast cancer, especially those with ESR1 mutations that make them resistant to other endocrine therapies. Unlike other treatments, it is taken orally and works by degrading the estrogen receptor, which helps inhibit tumor growth. ^{1 4 5 9 10}

What is the purpose of this trial?

This is a single-arm, phase II study examining elacestrant in the adjuvant treatment of patients with ER+ breast cancer who test positive for circulating tumor DNA (ctDNA) during the screening period of the trial.

Research Team

Mariya Rozenblit, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for men and women over 18 who had a certain type of breast cancer (ER+, HER2-) diagnosed between 5 to 15 years ago. They must have finished hormone therapy at least six months before the study starts and show positive signs of cancer in their blood.

Inclusion Criteria

My breast cancer was stage IIB or III, ER positive and HER2 negative.

I was diagnosed with ER+HER2- breast cancer between 5 and 15 years ago and finished hormone therapy.

I haven't taken hormone therapy for at least 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

Up to 12 months

1 visit (in-person)

Treatment

Participants receive elacestrant treatment for one year with ctDNA testing and imaging every three months

12 months

4 visits (in-person) for imaging and ctDNA testing

Follow-up

Participants are monitored for safety and effectiveness after treatment, with ctDNA testing every six months

12 months

2 visits (in-person) for ctDNA testing

Open-label extension (optional)

Participants may continue on elacestrant for an additional year or resume standard endocrine therapy

12 months

Treatment Details

Interventions

• Elacestrant

Trial Overview The trial is testing Elacestrant, a drug given after initial breast cancer treatment. It's for those with ER+ breast cancer who still have traces of cancer DNA in their blood. The study has no comparison group; all participants receive Elacestrant.

Participant Groups

Group I: Single Arm Experimental Treatment 1 Intervention

Administration of elacestrant will follow the FDA approved dose and schedule for patients with ER+ metastatic breast cancer. Elacestrant 345 mg will be administered orally once daily for 12 cycles or until disease progression or unacceptable toxicity

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Stemline Therapeutics, Inc.

Industry Sponsor

Trials

24

Recruited

6,500+

Findings from Research

Elacestrant, a selective estrogen receptor degrader, was found to be safe and well tolerated in a study involving 140 postmenopausal women, with doses up to 1000 mg daily not reaching the maximum tolerated dose.

The drug showed good oral bioavailability and a half-life of 27 to 47 hours, allowing for once-daily dosing, while effectively engaging estrogen receptors and demonstrating some ability to cross the blood-brain barrier.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. Conlan, MG., de Vries, EFJ., Glaudemans, A., et al.[2021]

The phase I trial assessed the safety and efficacy of elacestrant, a selective estrogen receptor degrader, specifically in patients with breast cancer.

This study represents an important step in evaluating new treatment options for breast cancer, focusing on a novel mechanism of action that targets estrogen receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Signs of Response to Elacestrant Seen in ER+ HER2- Breast Cancer. [2021]

In a phase III trial involving 477 patients with ER-positive/HER2-negative advanced breast cancer, elacestrant significantly improved progression-free survival (PFS) compared to standard-of-care endocrine therapy, with a hazard ratio of 0.70 for all patients and 0.55 for those with ESR1 mutations.

While elacestrant showed promising efficacy, it was associated with a higher rate of treatment-related adverse events, including nausea, and a greater percentage of patients discontinuing treatment due to side effects compared to standard therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. Bidard, FC., Kaklamani, VG., Neven, P., et al.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and pharmacokinetics of elacestrant. Beumer, JH., Foldi, J.[2023]

Elacestrant was approved by the FDA for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, highlighting its targeted approach for patients who have not responded to prior endocrine therapy.

The summary includes important details about elacestrant's mechanism of action and safety profile, which are crucial for understanding its role in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Approval of Elacestrant as a Selective Estrogen Receptor Degrader for the Treatment of Metastatic Breast Cancer. De, SK.[2023]

Elacestrant (RAD-1901) is a selective estrogen receptor degrader that was approved by the USFDA for treating ER+ HER2-positive breast cancer, demonstrating anticancer activity in both laboratory and animal models.

The review discusses Elacestrant's development, including its medicinal chemistry, mechanism of action, and safety profile based on clinical trial data, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. Bhatia, N., Thareja, S.[2023]

Elacestrant, an oral selective estrogen receptor downregulator, was approved by the FDA in January 2023 for treating hormone receptor positive (HR+) HER2- advanced breast cancer, showing improved progression-free survival in patients with ESR1 mutations who had previously failed treatment with CDK 4/6 inhibitors and endocrine therapy.

Clinical trials indicate that elacestrant has a safety profile comparable to existing endocrine therapies and provides an effective alternative treatment option, especially for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. Hageman, E., Lussier, ME.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and Pharmacodynamic Studies of Elacestrant, A Novel Oral Selective Estrogen Receptor Degrader, in Healthy Post-Menopausal Women. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Elacestrant Prolongs Progression-Free Survival in Advanced Breast Cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Early Signs of Response to Elacestrant Seen in ER+ HER2- Breast Cancer. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacology and pharmacokinetics of elacestrant. [2023]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

First Approval of Elacestrant as a Selective Estrogen Receptor Degrader for the Treatment of Metastatic Breast Cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. [2023]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating Elacestrant in the Management of ER-Positive, HER2-Negative Advanced Breast Cancer: Evidence to Date. [2023]

10. England pubmed.ncbi.nlm.nih.gov

EMERALD: Phase III trial of elacestrant (RAD1901) vs endocrine therapy for previously treated ER+ advanced breast cancer. [2020]