The goal of this research study is to compare a combination of two drugs, capecitabine and elacestrant to capecitabine alone as a treatment for advanced estrogen receptor-positive (ER+) breast cancer. This study is designed for participants with cancer that has previously stopped responding to medication in the class of therapy called CDK 4/6 inhibitors, including palbociclib, ribociclib, or abemaciclb.
The names of the study drugs involved in this study are:
* Elacestrant (a type of selective estrogen receptor degrader) * Capecitabine (a type of fluoropyrimidine antimetabolite)
Participants must have histologically confirmed estrogen receptor-positive (ER+), HER2-negative metastatic or locally recurrent unresectable (advanced) invasive breast cancer. ER and HER2 measurements should be performed according to institutional guidelines in a CLIA-approved setting. ER must be ≥ 10% on the most recent biopsy in which receptor testing was performed. Cutoff values for positive/negative HER2 staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.
Participants must have standard of care ctDNA sequencing testing documenting ESR1 and TP53 mutation status. In patients without ESR1 mutation, this result must be from within 3 months.
ESR1 mutations that are considered pathogenic are: E380Q, V422del, S436P, L536H, L536P, L536R, Y537C, Y537D, Y537N, Y537S, D538G
TP53 mutations that are considered pathogenic as determined by a CLIA certified laboratory
Participants who have had endocrine and/or biologic therapy < 14 days prior to entering the study or those who have not recovered from any prior treatment-related toxicities (must recover to no more than grade 1; alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 toxicity not constituting a safety risk based on investigator's judgment are acceptable). This is to minimize risk of drug-drug interactions and clarify etiology of future toxicities.
Participants who are receiving concurrent therapy with other investigational agents. This is to minimize risk of drug-drug interactions and clarify etiology of future toxicities.
Rapidly progressive, symptomatic, visceral spread of disease placing participant at risk of life- threatening complications in the short term. It is likely that these patients will not benefit from this regimen.
History of dihydropyrimidine dehydrogenase (DPD) deficiency. Patients with this deficiency are prone to significant toxicity from capecitabine.
Sequential
Capecitabine
DrugA fluoropyrimidine carbamate, tablet taken orally, per standard of care.
Elacestrant
DrugA selective estrogen receptor degrader, tablet taken orally, per standard of care
Progression Free Survival (PFS) in ESR1 mutant population
PFS based on the Kaplan-Meier method is defined as the time from study randomization to disease progression per RECIST 1.1 or death. Patients alive without disease progression are censored at the date of last disease evaluation.
Progression Free Survival (PFS) in intention to treat (ITT) population
PFS based on the Kaplan-Meier method is defined as the time from study randomization to disease progression per RECIST 1.1 or death. Patients alive without disease progression are censored at the date of last disease evaluation.
Overall Survival (OS) in ESR1 mutant population
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from randomization to death due to any cause or censored at date last known alive.
Objective Response Rate in ESR1 mutant population
The objective response rate is defined as the rate of patients with a complete response or partial response, calculated using RECIST 1.1. The best overall response is the best response recorded from the start of treatment until disease progression/recurrence.
Clinical benefit rate (CBR) in ESR1 mutant population
The clinical benefit rate is defined as the rate of patients with a complete response (CR), partial response (PR), or stable disease (SD) ≥24 weeks, calculated using RECIST 1.1.
Second progression event (PFS2) in ESR1 mutant population
PFS2 based on the Kaplan-Meier method is defined as the time from study randomization to second disease progression, according to RECIST 1.1, or death after first progression.
Overall survival (OS) ESR1 mutation not detected population
Overall Survival (OS) based on the Kaplan-Meier method is defined as the time from randomization to death due to any cause or censored at date last known alive.
Progression-free survival rate (PFS)
PFS based on the Kaplan-Meier method is defined as the time from study randomization to disease progression per RECIST 1.1 or death. Patients alive without disease progression are censored at the date of last disease evaluation.
Second progression event (PFS2)
PFS2 based on the Kaplan-Meier method is defined as the time from study randomization to second disease progression, according to RECIST 1.1, or death after first progression.
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Kristina A. Fanucci
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
Stemline Therapeutics, Inc.
Collaborator
Johns Hopkins University
Collaborator
Translational Breast Cancer Research Consortium
Collaborator
Menarini Group
Collaborator
Gateway for Cancer Research
Collaborator
Terri Brodeur Breast Cancer Foundation
Collaborator
