EVERST- Everolimus After Alpelisib in Women With Hormone Receptor-positive (HR+) Metastatic Breast Cancer (MBC) (MBC)
EVERST- Everolimus After Alpelisib in Women With HR+ MBC- This Phase II, Open-label, Single-arm, Study Investigates the Clinical Benefit of Everolimus Combined With Endocrine Therapy. in Hormone Receptor-positive (HR+), Metastatic Breast Cancer Patients Who Progressed on Prior PI3K Inhibitor Therapy With Endocrine Therapy. The Trial Aims to Determine if Sequential Inhibition of the PI3K/AKT/mTORC1 Pathway Retains Efficacy Post-PI3K Inhibitor Resistance, Hypothesizing That Everolimus Will Demonstrate a Response Rate Exceeding the Historical 9.5% Observed in the BOLERO2 Trial.
Study Overview
Status
Conditions
Detailed Description
Detailed Description The study employs a two-stage design to evaluate the primary endpoint of clinical response rate (complete/partial response per RECIST v1.1). Stage 1 will enroll 19 patients with measurable disease; if no responses are observed, the trial terminates. If ≥1 response occurs, 24 additional patients will be enrolled (total N=43), with success defined as ≥2 responses. Secondary endpoints include progression-free survival (PFS), clinical benefit rate (CBR), and biomarker analysis via longitudinal ctDNA profiling to identify genomic drivers of resistance/sensitivity. Eligible participants receive everolimus (10 mg/day) + ET until progression, unacceptable toxicity, or withdrawal. Tumor assessments occur every 8 weeks, with toxicity monitoring.
Study Design
Intervention Model: Single-group assignment
Primary Purpose: Treatment
Phase: II
Allocation: Non-randomized
Masking: None (open-label)
Outcome Measures
Primary: Objective response rate (ORR).
Secondary:
PFS (time from treatment initiation to progression/death).
CBR (proportion with CR/PR or stable disease ≥24 weeks).
Biomarker correlation (e.g., ESR1 mutations, PTEN alterations) via ctDNA analysis.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Breast Cancer coordinator Breast Cancer coordinator
- Phone Number: 972-03-6974092
- Email: hananm@tlvmc.gov.il
Study Locations
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Tel Aviv, Israel
- Recruiting
- Ichilov-Sourasky Medical Center
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Contact:
- Hanan Mansour Breast cancer study coordinator
- Phone Number: 97236974062
- Email: hananm@tlvmc.gov.il
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- HR+MBC with PI3Kmut Post CDK 4/6+ET Post PI3K inhibitor+ET
Exclusion Criteria:
- Women who didn't receive anti-PI3K
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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HR+MBC post Alpelisib
Patients with HR+MBC post Alpelisib treatment who are scheduled to receive Everolimus with endocrine therapy, an additional blood sample is collected for biomarker evaluation.
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Patients receive standard of care treatment as prescribed by their treating physician.
This study only observes the outcomes and does not alter the treatment regimen, dosing, or schedule."
"A supplementary blood sample is collected from participants to analyze genetic and molecular biomarkers, aiming to identify potential correlations between these markers and clinical response to the standard treatment."
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
ORR
Time Frame: Response rate- From enrollment to the first scan at 8-12 weeks
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Objective response rate -best response rate in the first scan 8-12 weeks from day1
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Response rate- From enrollment to the first scan at 8-12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
PFS
Time Frame: From date of enrollment until the date of first documented progression, assessed up to 24 months.
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Time from Day 1 to progression, an average of 16 weeks
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From date of enrollment until the date of first documented progression, assessed up to 24 months.
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CBR Clinical Benefit Rate
Time Frame: Through the end of the study, assessed up to 24 months.
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Proportion with CR/PR or stable disease ≥24 weeks
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Through the end of the study, assessed up to 24 months.
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Organic Chemicals
- Pharmaceutical Preparations
- Investigative Techniques
- Dosage Forms
- Specimen Handling
- Clinical Laboratory Techniques
- Diagnostic Techniques and Procedures
- Diagnosis
- Punctures
- Surgical Procedures, Operative
- Biological Factors
- Health Services
- Health Care Facilities Workforce and Services
- Preventive Health Services
- Macrolides
- Lactones
- Sirolimus
- Genetic Techniques
- Genetic Services
- Diagnostic Services
- Everolimus
- Tablets
- Genetic Testing
- Blood Specimen Collection
- Biomarkers
Other Study ID Numbers
- TLV-0295-21
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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