Hormone Receptor Positive Breast Cancer
Conditions
Keywords
mTOR inhibitor, Hormone receptor positive breast cancer, PI3K inhibitor
Brief summary
This phase II, open-label, single-arm, study investigates the clinical benefit of everolimus combined with endocrine therapy (ET) in hormone receptor-positive (HR+), metastatic breast cancer (MBC) patients who progressed on prior PI3K inhibitor therapy (+ ET). 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.
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.
Interventions
DRUGEverolimus (Afinitor) tablets with endocrine therapy
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."
PROCEDUREBlood draw for biomarker and genetic analysis
"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."
Sponsors
Tel-Aviv Sourasky Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HR+MBC with PI3Kmut Post CDK 4/6+ET Post PI3K inhibitor+ET
Exclusion criteria
* Women who didn't receive anti-PI3K
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | Response rate- From enrollment to the first scan at 8-12 weeks | Objective response rate -best response rate in the first scan 8-12 weeks from day1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | From date of enrollment until the date of first documented progression, assessed up to 24 months. | Time from Day 1 to progression, an average of 16 weeks |
| CBR Clinical Benefit Rate | Through the end of the study, assessed up to 24 months. | Proportion with CR/PR or stable disease ≥24 weeks |
Countries
Israel
Contacts
CONTACTBreast Cancer coordinator Breast Cancer coordinator
Outcome results
None listed