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NCT Number: NCT07646171

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

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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Key information

Conditions

Hormone Receptor Positive Breast Cancer

Age range

21 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Ichilov-Sourasky Medical Center

Tel Aviv, Israel

Location status: Recruiting

Location contact

Hanan Mansour Breast cancer study coordinator

CONTACT

[email protected]

97236974062

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Women who didn't receive anti-PI3K

Treatment and study plan

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."

Primary outcomes

  1. ORR

    Time frame: 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

  1. PFS

    Time frame: 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

  2. CBR Clinical Benefit Rate

    Time frame: Through the end of the study, assessed up to 24 months.

    Proportion with CR/PR or stable disease ≥24 weeks

Study contacts

Contact information is provided by the study sponsor or research team.

Breast Cancer coordinator Breast Cancer coordinator

CONTACT

[email protected]

972-03-6974092

Sponsors and collaborators

Lead sponsor

Tel-Aviv Sourasky Medical Center

Other Gov

Registry information

Official study 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.

Acronym: MBC

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Jun 12, 2026
Registry last updated
Jun 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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