Elacestrant Combinations for Breast Cancer

(ELEVATE Trial)

Recruiting at 115 trial locations

Overseen By Stemline Trials

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Stemline Therapeutics, Inc.

Must be taking: LHRH agonists

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: CNS metastases, Visceral spread, BRCA mutation, others

No Placebo Group

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This is a multicenter, Phase 1b/2 trial. The phase 1b part of the trial aims to determine the RP2D of elacestrant when administered in combination with alpelisib, everolimus, palbociclib, abemaciclib, and ribociclib. The Phase 2 part of the trial will evaluate the efficacy and safety of the various combinations in patients with ER+/HER2- advanced/metastatic breast cancer.

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

The trial requires that you stop taking certain medications before starting, such as anti-cancer therapies, strong or moderate inducers or inhibitors of a specific liver enzyme (CYP3A4), and certain herbal preparations. There is a 'washout' period (time without taking these medications) of 14 days or 5 half-lives, whichever is shorter, before the first dose of trial therapy.

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

Elacestrant has shown effectiveness in treating ER-positive, HER2-negative breast cancer, especially in patients with ESR1 mutations, by degrading estrogen receptors and inhibiting tumor growth. It has been approved by the FDA and demonstrated improved progression-free survival in clinical trials, particularly when combined with other drugs like palbociclib or everolimus. ^{1 2 3 4 5}

What safety data exists for Elacestrant in breast cancer treatment?

Elacestrant has been evaluated in clinical trials and is generally considered safe for use in humans with breast cancer, as it was approved by the FDA based on improved progression-free survival in patients. However, it can interact with certain medications and may require dose adjustments in people with liver issues. ^{1 2 3 5 6}

What makes the drug Elacestrant unique for breast cancer treatment?

Elacestrant is unique because it is the first orally available selective estrogen receptor degrader (SERD) approved for treating ER-positive, HER2-negative breast cancer with ESR1 mutations, offering a new option for patients who have progressed after endocrine therapy. ^{1 2 3 5 6}

Eligibility Criteria

This trial is for adults with ER+/HER2- advanced/metastatic breast cancer who've had up to two hormonal therapies, one with a CDK4/6 inhibitor. They must have good organ function and performance status, no severe allergies to the drugs being tested, and agree to contraception if of childbearing potential. Those with certain prior treatments or health conditions are excluded.

Inclusion Criteria

My cancer has a PIK3CA mutation.

Patient has signed the informed consent before all study specific activities are conducted.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have any severe ongoing infections.

QTcF values ≥450 msec.

I have been treated with everolimus before.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1b Treatment

Determine the RP2D of elacestrant in combination with other drugs, with 1-3 cohorts of 6 DLT-evaluable patients each

28 days

Multiple visits for dose-limiting toxicity evaluation

Phase 2 Treatment

Evaluate the efficacy and safety of elacestrant in combination with other drugs in patients with ER+/HER2- advanced/metastatic breast cancer

6 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 months

Treatment Details

Interventions

• Alpelisib (PI3K Inhibitor)
• Elacestrant (Selective Estrogen Receptor Degrader (SERD))
• Everolimus (mTOR Inhibitor)
• Palbociclib (CDK4/6 Inhibitor)
• Ribociclib (CDK4/6 Inhibitor)

Trial Overview The study tests Elacestrant in combination with other cancer drugs (Alpelisib, Everolimus, Ribociclib, Palbociclib) to find the best dose and assess safety/effectiveness against metastatic breast cancer. It's an open-label trial where everyone knows what treatment they're getting.

Participant Groups

Group I: Phase 1b Arm E: Experimental Treatment 2 Interventions

Elacestrant Dihydrochloride 300 mg, 400 mg + Capivasertib 200 mg, 320 mg, 400 mg

Group II: Phase 1b Arm D: elacestrant with either palbociclib, abemaciclib, or ribociclib (no prior CDK4/6i) Experimental Treatment 4 Interventions

Elacestrant Dihydrochloride 300 mg or 400 mg + Palbociclib 100 mg,125 mg OR The recommended Phase 2 dose for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384) Elacestrant 86 mg, 172 mg, 258 mg + Ribociclib 400 mg or possibly 600 mg

Group III: Phase 1b Arm C: elacestrant with abemaciclib or ribociclib: Experimental Treatment 3 Interventions

Elacestrant Dihydrochloride 100 mg, 200 mg, 300 mg + Ribociclib 400 mg or possibly 600 mg The recommended Phase 2 dose for the combination of elacestrant and abemaciclib is evaluated in the ongoing ELECTRA trial (ClinicalTrials.gov Identifier: NCT04791384)

Group IV: Phase 1b Arm B: elacestrant with everolimus Experimental Treatment 2 Interventions

Elacestrant Dihydrochloride 300 mg or 400 mg + Everolimus 5.0 mg, 7.5 mg or possibly 10 mg

Group V: Phase 1b Arm A: elacestrant with alpelisib Experimental Treatment 2 Interventions

Elacestrant Dihydrochloride 300 mg or 400 mg + Alpelisib 250 mg or 300 mg

Who Is Running the Clinical Trial?

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Stemline Therapeutics, Inc.

Lead Sponsor

Trials

24

Recruited

6,500+

Findings from Research

Elacestrant (ORSERDU™) is a newly approved oral medication for treating advanced or metastatic breast cancer in postmenopausal women and adult men with specific estrogen receptor mutations, following at least one line of endocrine therapy.

The drug specifically targets estrogen receptor-positive, HER2-negative breast cancer, and its approval in the USA marks a significant milestone in its development, with ongoing regulatory assessments in the EU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: First Approval. Hoy, SM.[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 (RAD1901) effectively degrades estrogen receptors and inhibits the growth of estrogen receptor-positive (ER+) breast cancer cells in both laboratory and patient-derived models, showing significant antitumor activity.

The combination of elacestrant with other therapies like palbociclib or everolimus enhances its efficacy, suggesting it could be a valuable treatment option for patients with ER+ breast cancer, including those with resistant mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Bihani, T., Patel, HK., Arlt, H., et al.[2018]

In the phase III EMERALD trial, elacestrant, an oral selective estrogen receptor degrader, showed a statistically significant improvement in progression-free survival for patients with ER-positive/HER2-negative breast cancer.

This benefit was observed in patients who had already been treated with endocrine therapy and a CDK4/6 inhibitor, indicating elacestrant's potential as a valuable treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel SERD Has PFS Edge against Breast Cancer. [2022]

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]

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]

References

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

Elacestrant: First Approval. [2023]

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

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

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

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. [2018]

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

Novel SERD Has PFS Edge against Breast Cancer. [2022]

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

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

6. Germany pubmed.ncbi.nlm.nih.gov

Pharmacology and pharmacokinetics of elacestrant. [2023]