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

NCT07646171 — Recruiting, 19 participants, Tel-Aviv Sourasky Medical Center
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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.

RegistryNCT07646171, acronym MBC
StatusRecruiting
Study typeObservational
Enrollment19 (Estimated)
SponsorTel-Aviv Sourasky Medical Center (Other gov)
ConditionsHormone Receptor Positive Breast Cancer
InterventionsEverolimus (Afinitor) tablets with endocrine therapy, Blood draw for biomarker and genetic analysis (Drug, procedure)
Datesstart 2022-09-01, primary completion 2026-12-31 (estimated), completion 2027-12-31 (estimated), first posted 2026-06-12, last updated 2026-06-12
Locations1 site in Israel

Related Papers Related Patents Related Grants Related Experts
All trials for Hormone Receptor Positive Breast Cancer All trials of Everolimus (Afinitor) tablets with endocrine therapy All trials of Blood draw for biomarker and genetic analysis

-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.

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+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.

+Arms and interventions

ArmTypeInterventionsDescription
HR+MBC post AlpelisibDrug: Everolimus (Afinitor) tablets with endocrine therapy; Procedure: Blood draw for biomarker and genetic analysisPatients with HR+MBC post Alpelisib treatment who are scheduled to receive Everolimus with endocrine therapy, an additional blood sample is collected for biomarker evaluation.
  • Everolimus (Afinitor) tablets with endocrine therapy (Drug): 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."
  • Blood draw for biomarker and genetic analysis (Procedure): "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."

+Outcome measures

Primary outcomes

  • 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 outcomes

  • 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

+Eligibility

Sex: All, ages: 21 Years to any

Inclusion Criteria:

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

Exclusion Criteria:

* Women who didn't receive anti-PI3K

+Locations (1)

FacilityCityCountryStatus
Ichilov-Sourasky Medical CenterTel AvivIsraelRecruiting