EVERST- Everolimus After Alpelisib in Women With Hormone Receptor-positive (HR+) Metastatic Breast Cancer (MBC)

Official title

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.

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.

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

• Drug Everolimus (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."
• Procedure Blood 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."

Primary outcome measures

• ORR [Time frame: Response rate- From enrollment to the first scan at 8-12 weeks]

Secondary outcome measures (2)

• PFS [Time frame: From date of enrollment until the date of first documented progression, assessed up to 24 months.]
• CBR Clinical Benefit Rate [Time frame: Through the end of the study, assessed up to 24 months.]

Eligibility criteria

Inclusion criteria

• HR+MBC with PI3Kmut Post CDK 4/6+ET Post PI3K inhibitor+ET

Exclusion criteria

• Women who didn't receive anti-PI3K

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Israel · 1 center

• Ichilov-Sourasky Medical Center — Tel Aviv

Identifiers

NCT: NCT07646171 · TLV-0295-21

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗