Breast CancerPhase 2NCT02236572
Neoadj ph 2 AI Plus Everolimus in Postmenopausal Women w/ ER Pos/HER2 Neg, Low Risk Score
A Phase 2 study testing Everolimus in people with Breast Cancer, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to see whether adding everolimus to hormone treatment before breast surgery will increase the chances of shrinking the breast cancer in those patients with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or less), compared to prior experience with hormone… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Nov 2014to 1 Mar 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a histologically confirmed diagnosis of hormone receptor positive, HER2 negative invasive breast carcinoma.
- Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP 2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by immunohistochemistry. Estrogen and/or progesterone receptor results by Oncotype Dx will not be accepted.
- Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (must be a ratio of < 2), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.
- Patients must not have had prior ipsilateral breast-conserving surgery or total mastectomy and be eligible for neoadjuvant treatment.
- Clinical Stage II-IIIC (T2-4 N0-3 M0) by mammogram, ultrasound or MRI
- Baseline Oncotpye Dx recurrence score < 25.
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- Staging studies with a CT scan of the chest and abdomen and bone scan, or a PET/CT is required for clinical stage III, and are considered optional for stage II breast cancers.
- Patients with multifocal, multicentric and synchronous bilateral breast cancers are allowed:
- Multifocal disease is defined as more than one invasive cancer < 2 cm from the largest lesion within the same breast quadrant.
- Multicentric disease is defined as more than one invasive cancer ≥ 2 cm from the largest lesion within the same breast quadrant or more than one lesion in different quadrants.
- Synchronous bilateral disease is defined as invasive breast cancer in both breasts, diagnosed within 30 days of each other.
- In patients with multicentric or bilateral invasive breast cancers, all sampled lesions must be hormone receptor-positive and HER2-negative. Any lesion measuring > 1 cm must have an Oncotype Dx and the score must be < 25. Lesions less than 1 cm in size are not required to have an Oncotype Dx. One lesion (typically the largest) should be designated as the target lesion for which clinical and radiographic response to the neoadjuvant therapy will be judged.
- Patients with a hormone receptor-positive, HER2-negative invasive cancer that meets study criteria may have ductal carcinoma in situ in another quadrant of the same breast or in the contralateral breast even if the DCIS is hormone receptor-negative.
- Patients must have adequate bone marrow function, as defined by peripheral granulocyte count of ≥ 1,500/mL, hemoglobin ≥ 9 g/dL and a platelet count ≥ 100,000/ mL within 28 days prior to registration.
- Patients must have adequate hepatic function obtained within 28 days prior to registration and documented by all of the following:
- Bilirubin ≤ 1.5 mg/dL (or ≤ 3.0 mg/dL if due to Gilbert's Syndrome)
- ALT and AST ≤ 1.5 x Institutional Upper Limit of Normal (IULN)
- Alkaline phosphatase ≤ 1.5 x IULN
- Patients must have adequate renal function with serum creatinine level ≤ IULN within 28 days prior to registration.
- Patients must have a fasting cholesterol ≤ 300 mg/dl OR ≤7.75 mmol/L and triglycerides ≤ 2.5 x IULN obtained within 28 days prior to registration. Patients may be on lipid lowering agents to reach these values.
- Patients must have a ECOG performance status of 0-2.
- Patients must be able to take oral medications.
- Postmenopausal women (women are considered post-menopausal and not of child-bearing potential if they are > 18 years of age and have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms or biochemically postmenopausal by estradiol and FSH levels) prior to enrollment, or have had surgical bilateral oophorectomy (with or without hysterectomy) prior to registration. Medical ovarian suppression with LHRH agonists to render a patient postmenopausal will not be acceptable.
- 16. Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent prior to any screening procedures in accordance with institutional and federal guidelines.
Who cannot join
- Patients must not have inflammatory breast cancer (T4d) and must not have metastatic breast cancer (Stage IV disease).
- Patients must not have prior exposure to mTOR inhibitors (e.g. rapamycin, everolimus, sirolimus, temsirolimus, deforolimus).
- Patients must not have prior treatment with any investigational drug within the preceding 28 days and must not be planning to receive any other investigational drug for the duration of the study.
- Patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
- Uncontrolled diabetes mellitus as defined by HbA1c >8% within 28 days prior to registration despite adequate therapy.
- Patients who have any severe and/or uncontrolled cardiac disease within ≤ 6 months prior to start of everolimus, including: unstable angina pectoris, Symptomatic congestive heart failure of New York heart Association Class III or IV, myocardial infarction, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
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- Patients must not have an organ allograft or other history of immune compromise.
- Patients must not be receiving chronic, systemic treatment with corticosteroids or other immunosuppressive agent. Topical or inhaled corticosteroids are allowed.
- Patients must not have a known history of HIV seropositivity
- Patients must not have a known diagnosis of hepatitis B or C. Patients with the following risk factors must have hepatitis screening pre-treatment:
- Blood transfusions prior to 1990
- Current or prior IV drug users
- Current or prior dialysis
- Household contact with a hepatitis B or C patient
- Current or prior high-risk sexual activity
- History of jaundice.
- Patients must not have any known uncontrolled underlying pulmonary disease or severely impaired lung function (spirometry and DLCO 50% or less of normal and O2 saturation 88% or less at rest on room air),
- Active (acute or chronic) or uncontrolled severe infection.
- Patients who have received live attenuated vaccines within 1 week of start of Everolimus, or have plans to receive such vaccination while on protocol treatment. Patient should also avoid close contact with others who have received live attenuated vaccines. Examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella and TY21a typhoid vaccines;
- Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing;
- Patients must not have taken within 14 days prior to registration , be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors, and/or CYP3A4 inducers.
- Patients with active bleeding diathesis.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Neoadjuvant Phase II Trial of Aromatase Inhibitors in Combination With Everolimus in Postmenopausal Women With Hormone Receptor Positive/HER2 Negative Breast Cancers With Low and Intermediate Risk (< 25) Oncotype Dx Recurrence Scores
The purpose of this study is to see whether adding everolimus to hormone treatment before breast surgery will increase the chances of shrinking the breast cancer in those patients with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or less), compared to prior experience with hormone therapy alone. Everolimus is a drug currently approved for use by the United States Food and Drug administration (FDA) for the treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is considered investigational for non-metastatic breast cancer patients.
Read the detailed description
This is a single arm open-labeled neoadjuvant phase II clinical trial evaluating everolimus in combination with an aromatase inhibitor in postmenopausal women with hormone receptor positive/HER2 negative breast cancers with low and intermediate risk (< 25) Recurrence Scores by Oncotype Dx.
- Conditions
- Breast Cancer
- Being tested
- Everolimus
- Keywords
- Postmenopausal, ER-positive, PR-positive, HER2-negative, Low and intermediate risk
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Aromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily:
- Anastrozole 1 mg
- Letrozole 2.5 mg
- Exemestane 25 mg
| Study group | Role | What they receive |
|---|---|---|
| Aromatase Inhibitor plus Everolimus | Experimental | Aromatase inhibitor plus everolimus by mouth daily for 26 weeks Receives: Drug: Everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor
(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.
Measured: up to 26 weeks
Secondary outcomes (2)
PEPI Score
To obtain the PEPI score, risk points for relapse-free survival (RFS) are assigned depending on the hazard ratio (HR) from the multivariable analysis. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. A HR in the range of 1 to 2 receives one risk point; a HR in the 2 to 2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model, ranges from 0 (best possible outcome) to 12 (worst possible outcome).
Measured: up to 26 weeks
Participant Ability to Tolerate Study Treatment With Minimal Side Effects
Adverse events (using CTCAE (4.0)) that begin or worsen after informed consent were recorded. Adverse events are itemized in the adverse events module (in terms of total events and total participants experiencing events). Presented are the total number of participants that experience adverse events. For clarification, counts of participants that experienced serious adverse events and counts of participants that experienced 'other' (not serious) adverse events are presented separately.
Measured: Up to 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2014 (estimated)
- Study start29 Nov 2014
- Primary completion1 Mar 2021
- Study completion1 Mar 2021
Why it stopped: Phase 2 of recruitment was contingent on 5 of 15 patients responding, which did not occur.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Lajos Pusztai, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02236572
- Sponsor's protocol ID
- 1405013982
- Status last verified
- Jan 2022
- First submitted
- 8 Sep 2014
- Last updated
- 1 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Neoadjuvant Phase II Trial of Aromatase Inhibitors in Combination With Everolimus in Postmenopausal Women With Hormone Receptor Positive/HER2 Negative Breast Cancers With Low and Intermediate Risk (< 25) Oncotype Dx Recurrence Scores
- ClinicalTrials.gov ID
- NCT02236572
- Acronym / sponsor ID
- 1405013982
- Conditions
- Breast Cancer
- Keywords
- Postmenopausal, ER-positive, PR-positive, HER2-negative, Low and intermediate risk
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Phase 2 of recruitment was contingent on 5 of 15 patients responding, which did not occur.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals
- Study start
- 29 Nov 2014 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 10 Sep 2014 (estimated)
- Results
- Posted 1 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to see whether adding everolimus to hormone treatment before breast surgery will increase the chances of shrinking the breast cancer in those patients with hormone-responsive breast cancer and a lower Oncotype DX® Recurrence Score ( 25 or less), compared to prior experience with hormone therapy alone. Everolimus is a drug currently approved for use by the United States Food and Drug administration (FDA) for the treatment of patients with advanced or metastatic kidney or breast cancer. Everolimus is considered investigational for non-metastatic breast cancer patients.
Detailed description
This is a single arm open-labeled neoadjuvant phase II clinical trial evaluating everolimus in combination with an aromatase inhibitor in postmenopausal women with hormone receptor positive/HER2 negative breast cancers with low and intermediate risk (< 25) Recurrence Scores by Oncotype Dx.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Aromatase Inhibitor plus Everolimus | Experimental | Drug: EverolimusAromatase inhibitor plus everolimus by mouth daily for 26 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Patients must have a histologically confirmed diagnosis of hormone receptor positive, HER2 negative invasive breast carcinoma.
- Tumors must be estrogen and/or progesterone receptor positive according to ASCO/CAP 2010 guidelines as either ER or PR ≥ 1% positive nuclear staining by immunohistochemistry. Estrogen and/or progesterone receptor results by Oncotype Dx will not be accepted.
- Tumors must be HER2 negative as defined according to ASCO/CAP 2013, as HER2 0 - 1+ by IHC or non-amplified FISH or CISH. If HER2 IHC is 2+, FISH/CISH must be performed and must not be positive (must be a ratio of < 2), but otherwise FISH/CISH is not required if IHC is 0 or 1+ by institutional standards.
- Patients must not have had prior ipsilateral breast-conserving surgery or total mastectomy and be eligible for neoadjuvant treatment.
- Clinical Stage II-IIIC (T2-4 N0-3 M0) by mammogram, ultrasound or MRI
Key exclusion criteria (22 listed)
- Patients must not have inflammatory breast cancer (T4d) and must not have metastatic breast cancer (Stage IV disease).
- Patients must not have prior exposure to mTOR inhibitors (e.g. rapamycin, everolimus, sirolimus, temsirolimus, deforolimus).
- Patients must not have prior treatment with any investigational drug within the preceding 28 days and must not be planning to receive any other investigational drug for the duration of the study.
- Patient may not have any impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of the drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
- Uncontrolled diabetes mellitus as defined by HbA1c >8% within 28 days prior to registration despite adequate therapy.
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 |
|---|---|---|
| EverolimusAromatase inhibitor plus everolimus by mouth daily for 26 weeks. All patients will begin treatment on Cycle 1 Day 1 with both the standard dose of one of the following 3 aromatase inhibitors ( physician's choice) plus everolimus 10 mg by mouth daily: * Anastrozole 1 mg * Letrozole 2.5 mg * Exemestane 25 mg | Drug | Aromatase Inhibitor plus Everolimus |
Primary outcome
Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor
Time frame: up to 26 weeks
(PEPI) preoperative endocrine prognostic index. The total PEPI score assigned to each patient is the sum of the risk points derived from the pT stage, pN stage, Ki67 level, and estrogen receptor status of the surgical specimen. An HR in the range of 1-2 receives one risk point; a HR in the 2-2.5 range, two risk points; a HR greater than 2.5, three risk points. The total risk point score for each patient is the sum of all the risk points accumulated from the four factors in the model. A lower PEPI score indicates lower risk for recurrence. A score of 0 is lowest risk for recurrence.
2 secondary outcomes
PEPI Score
Time frame: up to 26 weeks
Participant Ability to Tolerate Study Treatment With Minimal Side Effects
Time frame: Up to 26 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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. This study is not recruiting at the moment.
Lajos Pusztai, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Everolimus in people with Breast Cancer, run by Yale University at 1 site in United States.
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 24 inclusion and 22 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: stopped early, as of the sponsor's last update on 1 Feb 2022. 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 United States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Achievement of a PEPI Score of 0 Following Neoadjuvant Treatment With Everolimus and an Aromatase Inhibitor (time frame: up to 26 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 1 Feb 2022.