Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02291913|
Recruitment Status : Completed
First Posted : November 17, 2014
Results First Posted : February 17, 2020
Last Update Posted : February 17, 2020
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|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Everolimus Drug: Exemestane Drug: Tamoxifen Drug: Fulvestrant Drug: Anastrozole Drug: Letrozole Drug: Toremifine||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||48 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Open Label Study of Everolimus in Combination With Anti-estrogen Therapy in Hormone Receptor-Positive HER2-Negative Advanced Breast Cancer|
|Actual Study Start Date :||December 18, 2014|
|Actual Primary Completion Date :||January 31, 2019|
|Actual Study Completion Date :||January 31, 2019|
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.
Other Name: Afinitor
- 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).
- Number of Patients With Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: Up to 20 months ]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.
- 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 ]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.
- Number of Participants With CR, PR, or 6 Months of SD Also Called Clinical Benefit Rate (CBR) [ Time Frame: Up to 20 months ]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).
- 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 ]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.
- Median Overall Survival (OS) [ Time Frame: up to 3 years from first treatment ]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.
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||Female|
|Accepts Healthy Volunteers:||No|
- 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.
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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02291913
|United States, Florida|
|Florida Cancer Specialists-South|
|Fort Myers, Florida, United States, 33916|
|Memorial Cancer Center|
|Hollywood, Florida, United States, 33021|
|Woodlands Medical Specialists|
|Pensacola, Florida, United States, 32503|
|Florida Cancer Specialists-East|
|West Palm Beach, Florida, United States, 33401|
|United States, Indiana|
|Hope Cancer Center|
|Terre Haute, Indiana, United States, 47802|
|United States, Tennessee|
|Chattanooga, Tennessee, United States, 37404|
|Tennessee Oncology PLLC|
|Nashville, Tennessee, United States, 37203|
|United States, Texas|
|Center for Cancer and Blood Disorders|
|Fort Worth, Texas, United States, 76104|
|Study Chair:||Denise A. Yardley, MD||SCRI Development Innovations, LLC|
Documents provided by SCRI Development Innovations, LLC:
|Responsible Party:||SCRI Development Innovations, LLC|
|Other Study ID Numbers:||
SCRI BRE 212
|First Posted:||November 17, 2014 Key Record Dates|
|Results First Posted:||February 17, 2020|
|Last Update Posted:||February 17, 2020|
|Last Verified:||February 2020|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
|Product Manufactured in and Exported from the U.S.:||No|
ER-Positive Breast Cancer
HER2-Negative Breast Cancer
PR-Positive Breast Cancer
Neoplasms by Site
Protein Kinase Inhibitors
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Steroid Synthesis Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists