Elacestrant Combinations for Breast Cancer (ELEVATE Trial)
Recruiting in Palo Alto (17 mi)
+114 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Stemline Therapeutics, Inc.
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.
12345What 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.
12356What 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.
12356Eligibility 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.Participant Groups
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.
5Treatment groups
Experimental Treatment
Group I: Phase 1b Arm E:Experimental Treatment2 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 Treatment4 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 Treatment3 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 everolimusExperimental Treatment2 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 alpelisibExperimental Treatment2 Interventions
Elacestrant Dihydrochloride 300 mg or 400 mg + Alpelisib 250 mg or 300 mg
Elacestrant is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Orserdu for:
- ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
🇪🇺 Approved in European Union as Orserdu for:
- ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
New York Cancer and Blood SpecialistsPort Jefferson Station, NY
MD Anderson Cancer Center TexasHouston, TX
Texas Oncology - Baylor Charles A. Sammons Cancer CenterDallas, TX
NYU Langone HealthNew York, NY
More Trial Locations
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Who is running the clinical trial?
Stemline Therapeutics, Inc.Lead Sponsor
Stemline Therapeutics, Inc.Lead Sponsor
References
Elacestrant: First Approval. [2023]Elacestrant (ORSERDU™) is an orally available selective estrogen receptor degrader (SERD) being developed by Stemline Therapeutics, a subsidiary of Menarini Group, for the treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. In January 2023, elacestrant received its first approval for the treatment of postmenopausal women or adult men with ER-positive, HER2-negative, estrogen receptor 1 (ESR1)-mutated (as determined by a US FDA-approved test) advanced or metastatic breast cancer with disease progression following ≥ 1 line of endocrine therapy in the USA. A regulatory assessment of elacestrant for the treatment of ER-positive, HER2-negative advanced or metastatic breast cancer is currently underway in the EU. Development of elacestrant for the treatment of vasomotor symptoms has been discontinued. This article summarizes the milestones in the development of elacestrant leading to this first approval for this indication.
Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. [2023]Elacestrant (RAD-1901), a selective estrogen receptor degrader, was approved by USFDA on January 27, 2023, for the treatment of breast cancer. It has been developed by Menarini Group under the brand name Orserdu®. Elacestrant showed anticancer activity both in vitro and in vivo in ER+ HER2-positive breast cancer models. The present review delebrates the development stages of Elacestrant, with its medicinal chemistry, synthesis, mechanism of action, and pharmacokinetic studies. Clinical data and safety profile has also been discussed, including data from randomized trials.
Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. [2018]Purpose: Estrogen receptor-positive (ER+) breast cancers are typically treated with endocrine agents, and dependence on the ER pathway is often retained even after multiple rounds of antiestrogen therapy. Selective estrogen receptor degraders (SERD) are being developed as a strategy to more effectively target ER and exploit ER dependence in these cancers, which includes inhibiting both wild-type and mutant forms of ER. The purpose of this study was to evaluate the efficacy of a novel orally bioavailable SERD, elacestrant (RAD1901), in preclinical models of ER+ breast cancer.Experimental Design: Elacestrant was evaluated as a single agent and in combination with palbociclib or everolimus in multiple ER+ breast cancer models, including several patient-derived xenograft models.Results: Elacestrant induces the degradation of ER, inhibits ER-mediated signaling and growth of ER+ breast cancer cell lines in vitro and in vivo, and significantly inhibits tumor growth of multiple PDX models. Furthermore, we demonstrate that elacestrant in combination with palbociclib or everolimus can lead to greater efficacy in certain contexts. Finally, elacestrant exhibits significant antitumor activity both as a single agent and in combination with palbociclib in two patient-derived breast cancer xenograft models harboring ESR1 mutations.Conclusions: These data underscore the potential clinical utility of elacestrant as a single agent and as a combination therapy, for both early- and late-stage ER+ disease. Clin Cancer Res; 23(16); 4793-804. ©2017 AACR.
Novel SERD Has PFS Edge against Breast Cancer. [2022]In the phase III EMERALD trial, the investigational oral selective estrogen receptor degrader elacestrant offered a modest but statistically significant improvement in progression-free survival in patients with ER-positive/HER2-negative breast cancer previously treated with endocrine therapy and a CDK4/6 inhibitor.
Early Signs of Response to Elacestrant Seen in ER+ HER2- Breast Cancer. [2021]A phase I trial evaluated the selective estrogen receptor degrader elacestrant in breast cancer.
Pharmacology and pharmacokinetics of elacestrant. [2023]Elacestrant, a novel oral selective estrogen receptor (ER) degrader (SERD), was approved by the Food and Drug Administration (FDA) on January 27, 2023, for use in patients with ER and/or progesterone receptor (PR)-positive and HER2-negative metastatic breast cancer whose tumors harbor an ESR1 missense mutation (ESR1-mut), after at least one line of endocrine therapy (ET). The FDA made its decision based on the randomized phase 3 EMERALD trial, which met its primary endpoint of improved median progression-free survival (mPFS) with elacestrant monotherapy versus standard-of-care endocrine monotherapy in the overall intention to treat population; however, this benefit was largely driven by the ESR1-mut cohort. Elacestrant is a dose-dependent mixed ER agonist/antagonist, which at high doses acts as a direct ER antagonist as well as selective downregulator of ER. It is 11% bioavailable, primarily metabolized by CYP3A4 in the liver and excreted in feces. This leads to drug-drug interactions with strong CYP3A4 inhibitors and inducers, such as itraconazole and rifampin, respectively. In accordance with its clearance route, dose reduction is recommended in patients with moderate hepatic dysfunction but not in renal dysfunction. Studies evaluating elacestrant in severe hepatic dysfunction as well as in patients from racial and ethnic minority groups are ongoing. Overall, elacestrant is the first orally bioavailable SERD approved by the FDA for use in patients with metastatic breast cancer. Current clinical trials are ongoing evaluating it in the adjuvant setting in patients with early stage ER-positive breast cancers.