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Everolimus Combined With Anti-estrogen Therapy in Hormone-Receptor-Positive HER-2 Negative Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02291913
Recruitment Status : Active, not recruiting
First Posted : November 17, 2014
Last Update Posted : May 30, 2019
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Everolimus Drug: Exemestane Drug: Tamoxifen Drug: Fulvestrant Drug: Anastrozole Drug: Letrozole Drug: Toremifine Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 : January 7, 2015
Estimated Primary Completion Date : January 31, 2020
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: everolimus
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.
Drug: Everolimus
Other Name: Afinitor

Drug: Exemestane
Anti-estrogen therapy

Drug: Tamoxifen
Anti-estrogen therapy

Drug: Fulvestrant
Anti-estrogen therapy

Drug: Anastrozole
Anti-estrogen therapy

Drug: Letrozole
Anti-estrogen therapy

Drug: Toremifine
Anti-estrogen therapy

Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: up to 3 years ]
    All patients who received at least 1 cycle of study treatment and had at least 1 post-baseline assessment will be evaluable. PFS defined as the time from Day 1 of study drug administration to disease progression as defined by RECIST (Response Evaluation Criteria in Solid Tumors) v1.1 criteria, or death on study.

Secondary Outcome Measures :
  1. Number of patients with Adverse Events (AEs) as a Measure of Safety and Tolerability [ Time Frame: approximately 1 year from first treatment ]
    Assessments will be made through analysis of the reported incidence of treatment-emergent AEs.

  2. Overall Response Rate (ORR) [ Time Frame: every 8 weeks until discontinuation, estimated 1 year from first treatment ]
    The proportion of patients with observed complete response (CR) or partial response (PR) according to RECIST v1.1 criteria.

  3. Clinical Benefit Rate (CBR) [ Time Frame: approximately 1 year from first treatment ]
    The proportion of patients with CR + PR + Stable Disease (SD) x 6 months

  4. Duration of Response (DOR) [ Time Frame: every 8 weeks until discontinuation, estimated 1 year from first treatment ]
    Defined as time from first date of response (CR or PR) to disease progression or death as defined by RECIST v1.1 criteria.

  5. Overall Survival [ Time Frame: up to 3 years from first treatment ]
    Defined as from Day 1 of study drug administration to date of death due to any cause.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Histologic diagnosis of unresectable, locally recurrent or MBC.
  2. ER and/or PR-positive tumors with staining by immunohistochemistry (IHC) based on the most recent biopsy.
  3. 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.
  4. 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.

  5. 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.
  6. 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).
  7. 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.
  8. Adequate hematologic, hepatic and renal function.
  9. 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).
  10. Age ≥ 18 years.
  11. ECOG Performance Status score of 0-2.
  12. Life expectancy of ≥ 12 weeks.

Exclusion Criteria:

  1. Previous therapy or known intolerance/hypersensitivity with any approved or investigational mTOR inhibitor (e.g., temsirolimus, everolimus, sirolimus).
  2. Patients who are ≤21 days after their most recent chemotherapy and have not recovered from side effects.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.

Information from the National Library of Medicine

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 identifier (NCT number): NCT02291913

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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
Tennessee Oncology
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
Sponsors and Collaborators
SCRI Development Innovations, LLC
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Study Chair: Denise A. Yardley, MD SCRI Development Innovations, LLC

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Responsible Party: SCRI Development Innovations, LLC Identifier: NCT02291913     History of Changes
Other Study ID Numbers: SCRI BRE 212
First Posted: November 17, 2014    Key Record Dates
Last Update Posted: May 30, 2019
Last Verified: May 2019

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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
Keywords provided by SCRI Development Innovations, LLC:
ER-Positive Breast Cancer
HER2-Negative Breast Cancer
anti-estrogen therapy
PR-Positive Breast Cancer
Additional relevant MeSH terms:
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Estrogen Antagonists
Estrogen Receptor Modulators
Estrogen Receptor Antagonists
Selective Estrogen Receptor Modulators
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors