Overview
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.
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.
Eligibility
Inclusion Criteria:
- HR+MBC with PI3Kmut Post CDK 4/6+ET Post PI3K inhibitor+ET
Exclusion Criteria:
- Women who didn't receive anti-PI3K
