Breast CancerPhase 2NCT02291913
Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer
A Phase 2 study testing Everolimus, Exemestane and Tamoxifen in people with Breast Cancer, run by SCRI Development Innovations, LLC at 8 sites in United States.
Trial summary
Many patients with ER-positive or PR-positive breast cancer are treated with endocrine therapy. Although most ER/PR-positive tumors initially respond to hormonal therapy, patients often experience disease progression. Everolimus, in combination with exemestane, has shown activity in endocrine-resistant disease. 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, Exemestane and Tamoxifen
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 8 sitesUnited States
- Study dates
- 18 Dec 2014to 31 Jan 2019
- 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
- Histologic diagnosis of unresectable, locally recurrent or MBC.
- ER and/or PR-positive tumors with staining by immunohistochemistry (IHC) based on the most recent biopsy.
- Only 1 previous chemotherapy regimen for MBC. Patients progressing while receiving adjuvant endocrine therapy or progressing <12 months from completion of adjuvant endocrine therapy are eligible.
- Progressed on anti-estrogen therapy (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy) defined as:
- Recurrence while on, or within 12 months of end of anti-estrogen therapy for early stage breast cancer, or
- Progression while on, or within one month of anti-estrogen therapy for locally advanced or metastatic breast cancer.
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- Note: No washout for anti-estrogen therapy required. Anti-estrogen therapy does not have to be the last treatment prior to study entry.
- Post-menopausal or pre/peri-menopausal women on tamoxifen. LHRH agonists may be used to render ovarian suppression with postmenopausal ranges of estradiol or FSH per institutional guidelines.
- HER2-negative breast cancer, defined as follows:
- Fluorescent In Situ Hybridization (FISH)-negative (FISH ratio <2.0), or
- IHC 0-1+, or
- IHC 2-3+ AND FISH-negative (FISH ratio <2.0).
- Measureable disease as measured by Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1 or evaluable bone lesions, lytic or mixed, in absence of measureable disease by RECIST criteria.
- Adequate hematologic, hepatic and renal function.
- International normalized ratio (INR) ≤1.5 or prothrombin time (PT)/partial thromboplastin time (PTT) within normal limits (WNL) of the institution (if patient is not on anti-coagulation therapy).
- Age ≥ 18 years.
- ECOG Performance Status score of 0-2.
- Life expectancy of ≥ 12 weeks.
Who cannot join
- Previous therapy or known intolerance/hypersensitivity with any approved or investigational mTOR inhibitor (e.g., temsirolimus, everolimus, sirolimus).
- Patients who are ≤21 days after their most recent chemotherapy and have not recovered from side effects.
- Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of everolimus. For investigational drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the investigational drug and administration of everolimus is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days for metastatic disease prior to first dose of everolimus or has not recovered from side effects of such therapy.
- Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 2 weeks have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases.
- Patients with known active hepatitis B (HBV) or hepatitis C (HCV) infection. Patients with risk factors for hepatitis must have HBV DNA and HCV RNA testing by PCR, and are ineligible if these tests are positive.
- Patients receiving immunization with attenuated live vaccines within 1 week of study entry or during study period.
- NOTE: There are additional inclusion/exclusion criteria. The study center will determine patient eligibility and respond to any questions.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Tennessee Oncology
Chattanooga, Tennessee, 37404
Florida Cancer Specialists-South
Fort Myers, Florida, 33916
Center for Cancer and Blood Disorders
Fort Worth, Texas, 76104
Memorial Cancer Center
Hollywood, Florida, 33021
Tennessee Oncology PLLC
Nashville, Tennessee, 37203
Woodlands Medical Specialists
Pensacola, Florida, 32503
Hope Cancer Center
Terre Haute, Indiana, 47802
Florida Cancer Specialists-East
West Palm Beach, Florida, 33401
About this study
Official title: Phase II Open Label Study of Everolimus in Combination With Anti-estrogen Therapy in Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer
Many patients with ER-positive or PR-positive breast cancer are treated with endocrine therapy. Although most ER/PR-positive tumors initially respond to hormonal therapy, patients often experience disease progression. Everolimus, in combination with exemestane, has shown activity in endocrine-resistant disease. This study will evaluate the efficacy of Everolimus+ anti-estrogen therapy in patients with ER-positive metastatic breast cancer who have progressed after receiving anti-estrogen therapy.
Read the detailed description
This is a multi-centered, open-labeled, Phase II study on metastastic breast cancer (MBC). The patient population includes locally recurrent or MBC patients with cytologically or histologically confirmed hormone receptor-positive breast cancer who have demonstrated disease progression on prior anti-estrogen therapy or therapies. Investigators propose to evaluate the efficacy of Everolimus in patients with ER-positive (estrogen receptor-positive) metastatic breast cancer who have progressed on anti-estrogen therapy. Forty-six (46) patients are planned for enrollment in the trial.
- Conditions
- Breast Cancer
- Being tested
- Everolimus, Exemestane, Tamoxifen, Fulvestrant, Anastrozole
- Keywords
- ER-Positive Breast Cancer, HER2-Negative Breast Cancer, everolimus, anti-estrogen therapy, PR-Positive Breast Cancer, Afinitor
- 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
Also called Afinitor
ExemestaneDrug
Anti-estrogen therapy
TamoxifenDrug
Anti-estrogen therapy
FulvestrantDrug
Anti-estrogen therapy
AnastrozoleDrug
Anti-estrogen therapy
LetrozoleDrug
Anti-estrogen therapy
ToremifineDrug
Anti-estrogen therapy
| Study group | Role | What they receive |
|---|---|---|
| everolimus | Experimental | Everolimus will be administered at a dose of 10 mg PO daily combined with any one of the following anti-estrogen therapies on which the patient most recently progressed (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy). Anti-estrogen therapy will be administered at the US Food and Drug Administration (FDA) prescribed doses. Receives: Drug: Everolimus; Drug: Exemestane; Drug: Tamoxifen; Drug: Fulvestrant; Drug: Anastrozole; Drug: Letrozole; Drug: Toremifine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression Free Survival (PFS)
PFS is defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria, or death on study. Participants who are alive and free from disease progression will be censored at the date of last radiologic tumor assessment. Participants who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. Participants who do not have a post-baseline tumor assessment will be censored at the date of first treatment (Day 1).
Measured: up to 3 years
Secondary outcomes (5)
Number of Patients With Adverse Events (AEs) as a Measure of Safety and Tolerability
Assessments were made through analysis of the reported incidence of treatment-emergent AEs. All participants who received at least one dose of protocol treatment were followed for safety. Adverse events were collected from day of first dose to 30 days after last protocol treatment and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Measured: Up to 20 months
Number of Patients With an Objective Response (CR or PR) Also Called the Overall Response Rate (ORR).
Defined as the number of patients with objective evidence of complete or partial response (CR or PR) using RECIST version 1.1. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters.
Measured: every 8 weeks until discontinuation, up to 20 months
Number of Participants With CR, PR, or 6 Months of SD Also Called Clinical Benefit Rate (CBR)
The proportion of patients with Complete Response (CR) or Partial Response (PR) or 6 months or more of Stable Disease (SD). A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters. SD is not meeting the criteria for PR or a 20% increase in target lesions called Progressive Disease (PD).
Measured: Up to 20 months
Median Time From First Occurrence of CR or PR to Disease Progression or Death Also Called Duration of Response (DOR)
Only those patients who achieved Complete Response or Partial Response will be included in the summaries of DOR. DOR is defined as time from first date of response of CR or PR to disease progression or death as defined by RECIST v1.1 criteria. Participants who are alive and free from disease progression will be censored at the date of last tumor assessment. Patients who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. A CR is the complete disappearance of all target lesions. A PR is a decrease of 30% or more of the diameter(s) of all target lesions from the baseline sum of diameters.
Measured: every 8 weeks until discontinuation, up to 20 months
Median Overall Survival (OS)
Defined as the time from date of first study treatment to date of death due to any cause. Patients who are alive will be censored at the date of last known date alive.
Measured: up to 3 years from first treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2014 (estimated)
- Study start18 Dec 2014
- Primary completion31 Jan 2019
- Study completion31 Jan 2019
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.
- 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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- SCRI Development Innovations, LLC
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Denise A. Yardley, MD, Study chair, SCRI Development Innovations, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02291913
- Sponsor's protocol ID
- SCRI BRE 212
- Status last verified
- Feb 2020
- First submitted
- 10 Nov 2014
- Last updated
- 17 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Open Label Study of Everolimus in Combination With Anti-estrogen Therapy in Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT02291913
- Acronym / sponsor ID
- SCRI BRE 212
- Conditions
- Breast Cancer
- Keywords
- ER-Positive Breast Cancer, HER2-Negative Breast Cancer, everolimus, anti-estrogen therapy, PR-Positive Breast Cancer, Afinitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- SCRI Development Innovations, LLCUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- 18 Dec 2014 (actual)
- Primary completion
- 31 Jan 2019 (actual)
- Study completion
- 31 Jan 2019 (actual)
- First posted
- 17 Nov 2014 (estimated)
- Results
- Posted 17 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many patients with ER-positive or PR-positive breast cancer are treated with endocrine therapy. Although most ER/PR-positive tumors initially respond to hormonal therapy, patients often experience disease progression. Everolimus, in combination with exemestane, has shown activity in endocrine-resistant disease. This study will evaluate the efficacy of Everolimus+ anti-estrogen therapy in patients with ER-positive metastatic breast cancer who have progressed after receiving anti-estrogen therapy.
Detailed description
This is a multi-centered, open-labeled, Phase II study on metastastic breast cancer (MBC). The patient population includes locally recurrent or MBC patients with cytologically or histologically confirmed hormone receptor-positive breast cancer who have demonstrated disease progression on prior anti-estrogen therapy or therapies. Investigators propose to evaluate the efficacy of Everolimus in patients with ER-positive (estrogen receptor-positive) metastatic breast cancer who have progressed on anti-estrogen therapy. Forty-six (46) patients are planned for enrollment in the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| everolimus | Experimental | Drug: Everolimus, Drug: Exemestane, Drug: Tamoxifen, Drug: Fulvestrant, Drug: Anastrozole, Drug: Letrozole, Drug: ToremifineEverolimus will be administered at a dose of 10 mg PO daily combined with any one of the following anti-estrogen therapies on which the patient most recently progressed (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy). Anti-estrogen therapy will be administered at the US Food and Drug Administration (FDA) prescribed doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Histologic diagnosis of unresectable, locally recurrent or MBC.
- ER and/or PR-positive tumors with staining by immunohistochemistry (IHC) based on the most recent biopsy.
- Only 1 previous chemotherapy regimen for MBC. Patients progressing while receiving adjuvant endocrine therapy or progressing <12 months from completion of adjuvant endocrine therapy are eligible.
- Progressed on anti-estrogen therapy (tamoxifen, fulvestrant, anastrozole, letrozole, exemestane, toremifine, or LHRH agonists in conjunction with anti-estrogen therapy) defined as:
- Note: No washout for anti-estrogen therapy required. Anti-estrogen therapy does not have to be the last treatment prior to study entry.
Key exclusion criteria (8 listed)
- Previous therapy or known intolerance/hypersensitivity with any approved or investigational mTOR inhibitor (e.g., temsirolimus, everolimus, sirolimus).
- Patients who are ≤21 days after their most recent chemotherapy and have not recovered from side effects.
- Use of an investigational drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of everolimus. For investigational drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the investigational drug and administration of everolimus is required.
- Wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) administered ≤28 days or limited field radiation for palliation ≤7 days for metastatic disease prior to first dose of everolimus or has not recovered from side effects of such therapy.
- Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 2 weeks have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases.
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 |
|---|---|---|
| EverolimusAlso: Afinitor | Drug | everolimus |
| ExemestaneAnti-estrogen therapy | Drug | everolimus |
| TamoxifenAnti-estrogen therapy | Drug | everolimus |
| FulvestrantAnti-estrogen therapy | Drug | everolimus |
| AnastrozoleAnti-estrogen therapy | Drug | everolimus |
| LetrozoleAnti-estrogen therapy | Drug | everolimus |
| ToremifineAnti-estrogen therapy | Drug | everolimus |
Primary outcome
Median Progression Free Survival (PFS)
Time frame: up to 3 years
PFS is defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 criteria, or death on study. Participants who are alive and free from disease progression will be censored at the date of last radiologic tumor assessment. Participants who receive non-protocol therapy (subsequent therapy) prior to incurring an event will be censored at the date of last tumor assessment prior to the start of subsequent therapy. Participants who do not have a post-baseline tumor assessment will be censored at the date of first treatment (Day 1).
5 secondary outcomes
Number of Patients With Adverse Events (AEs) as a Measure of Safety and Tolerability
Time frame: Up to 20 months
Number of Patients With an Objective Response (CR or PR) Also Called the Overall Response Rate (ORR).
Time frame: every 8 weeks until discontinuation, up to 20 months
Number of Participants With CR, PR, or 6 Months of SD Also Called Clinical Benefit Rate (CBR)
Time frame: Up to 20 months
Median Time From First Occurrence of CR or PR to Disease Progression or Death Also Called Duration of Response (DOR)
Time frame: every 8 weeks until discontinuation, up to 20 months
Median Overall Survival (OS)
Time frame: up to 3 years from first treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2020.
- 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.
Denise A. Yardley, MD study chair
SCRI Development Innovations, LLC
8 sites 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, Exemestane and Tamoxifen in people with Breast Cancer, run by SCRI Development Innovations, LLC at 8 sites 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 18 inclusion and 8 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: finished, as of the sponsor's last update on 17 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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 17 Feb 2020). 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?
Median Progression Free Survival (PFS) (time frame: up to 3 years). 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 17 Feb 2020.