Hormone Receptor Positive Breast CancerMBCNCT07646171
EVERST- Everolimus After Alpelisib in Women With Hormone Receptor-positive (HR+) Metastatic Breast Cancer (MBC)
An observational study of Hormone Receptor Positive Breast Cancer, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Hormone Receptor Positive Breast Cancer
- What is being tested?
- Everolimus (Afinitor) tablets with endocrine therapy and Blood draw for biomarker and genetic analysis
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- How many people
- 19 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Sep 2022to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: HR+ MBC post CDK 4/6 inhibitors and anti PI3K inhibitor.
Who may be able to join
- HR+MBC with PI3Kmut Post CDK 4/6+ET Post PI3K inhibitor+ET
Who cannot join
- Women who didn't receive anti-PI3K
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Ichilov-Sourasky Medical Center
Tel Aviv
Hanan Mansour Breast cancer study coordinator, 97236974062, hananm@tlvmc.gov.il
About this study
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.
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.
Read the 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.
- Conditions
- Hormone Receptor Positive Breast Cancer
- Being tested
- Everolimus (Afinitor) tablets with endocrine therapy, Blood draw for biomarker and genetic analysis
- Keywords
- mTOR inhibitor, Hormone receptor positive breast cancer, PI3K inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Everolimus (Afinitor) tablets with endocrine therapyDrug
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 analysisProcedure or surgery
"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."
| Study group | Role | What they receive |
|---|---|---|
| HR+MBC post Alpelisib | Patients with HR+MBC post Alpelisib treatment who are scheduled to receive Everolimus with endocrine therapy, an additional blood sample is collected for biomarker evaluation. Receives: Drug: Everolimus (Afinitor) tablets with endocrine therapy; Procedure: Blood draw for biomarker and genetic analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
ORR
Objective response rate -best response rate in the first scan 8-12 weeks from day1
Measured: Response rate- From enrollment to the first scan at 8-12 weeks
Secondary outcomes (2)
PFS
Time from Day 1 to progression, an average of 16 weeks
Measured: From date of enrollment until the date of first documented progression, assessed up to 24 months.
CBR Clinical Benefit Rate
Proportion with CR/PR or stable disease ≥24 weeks
Measured: Through the end of the study, assessed up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2026
- Study start1 Sep 2022
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hormone Receptor Positive Breast CancerStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 19 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07646171
- Sponsor's protocol ID
- TLV-0295-21
- Acronym
- MBC
- Status last verified
- Jun 2026
- First submitted
- 15 May 2025
- Last updated
- 12 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be made available outside the primary research group to protect participant privacy and maintain confidentiality.
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT07646171
- Acronym / sponsor ID
- MBC / TLV-0295-21
- Conditions
- Hormone Receptor Positive Breast Cancer
- Keywords
- mTOR inhibitor, Hormone receptor positive breast cancer, PI3K inhibitor
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 19 participants (estimated)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 12 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HR+MBC post Alpelisib | – | Drug: 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. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- HR+ MBC post CDK 4/6 inhibitors and anti PI3K inhibitor.
Key inclusion criteria (1 listed)
- HR+MBC with PI3Kmut Post CDK 4/6+ET Post PI3K inhibitor+ET
Key exclusion criteria (1 listed)
- Women who didn't receive anti-PI3K
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Everolimus (Afinitor) tablets with endocrine therapyPatients 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." | Drug | HR+MBC post Alpelisib |
| 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." | Procedure or surgery | HR+MBC post Alpelisib |
Primary outcome
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
2 secondary outcomes
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be made available outside the primary research group to protect participant privacy and maintain confidentiality.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hormone Receptor Positive Breast Cancer, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Breast Cancer coordinator Breast Cancer coordinator (972-03-6974092, hananm@tlvmc.gov.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ORR (time frame: Response rate- From enrollment to the first scan at 8-12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2026.