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)
This is a Phase II, multi-center, open-label, randomized study comparing a combination of two drugs, capecitabine and elacestrant, to capecitabine alone as a treatment for advanced estrogen receptor-positive (ER+) Human Epidermal Growth Factor Receptor 2 negative (HER2-) 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. Participants will be randomized into one of two study groups: Arm A Capecitabine and Elacestrant versus Arm B Capecitabine alone. Randomization means a participants is placed into a study group by chance. The U.S. Food and Drug Administration (FDA) has approved capecitabine as a treatment option for advanced estrogen receptor-positive (ER+) Human Epidermal Growth Factor Receptor 2 negative (HER2-) breast cancer. The FDA has approved elacestrant for metastatic breast cancer with an ESR1 mutation. Elacestrant is not FDA approved for participants whose cancer does not have ESR1 mutation and it is possible elacestrant may not be as effective or effective at all in participants whose tumors do not have an ESR1 mutation. The FDA has not approved Elacestrant and Capecitabine to be given together. The research study procedures include screening for eligibility, in-clinic visits, questionnaires, blood tests, urine tests, Computerized Tomography (CT) scans, Magnetic Resonance Imaging (MRI) scans, and electrocardiograms (ECGs). It is expected that about 297 people will take part in this research study. Stemline, a Menarini Group Company, is supporting this research study by providing the study drugs, elacestrant, and funding. This study is also being supported by Johns Hopkins University on behalf of the Translational Breast Cancer Research Consortium (TBCRC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
297
A fluoropyrimidine carbamate, tablet taken orally, per standard of care.
A selective estrogen receptor degrader, tablet taken orally, per standard of care
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGProgression 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.
Time frame: Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles.
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.
Time frame: Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles.
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.
Time frame: Follow up or other contact every 2 months for 24 months until time of second progression, then every 6 months for 5 years
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.
Time frame: Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles
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.
Time frame: Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles
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.
Time frame: Follow up or other contact every 2 months for a total of 24 months or until progressive disease
Overall survival (OS) in ITT 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.
Time frame: Follow up or other contact every 2 months for 24 months until time of second progression, then every 6 months for 5 years
Objective Response Rate in ITT population
The objective response rate is defined as the rate of patients with a complete response or partial response, calculated using RECIST 1.1.
Time frame: Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles
Clinical benefit rate (CBR) in ITT 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.
Time frame: Tumor measurements are repeated every 3 cycles (each cycle is 21 days) for the first 9 cycles. After cycle 9 tumor measurements will be performed every 4 cycles
Second progression event (PFS2) in ITT 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.
Time frame: Follow up or other contact every 2 months for a total of 24 months or until progressive disease
Safety and tolerability of capecitabine in combination with elacestrant
Assessment of toxicities and lab values categorized and graded according to CTCAE v5.0
Time frame: Assessment will occur once per cycle (each cycle is 21 days) for the first 9 cycles, then once every other cycle starting with cycle 10
Impact of treatment with capecitabine plus elacestrant versus capecitabine alone on quality of life
evaluation with PRO-CTCAE and FACT-ES survey instruments
Time frame: Once every 2 cycles (each cycle is 21 days) for the first 4 cycles, every 3 months for months 3-12 on trial, then every 6 months for months 12+ on trial
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