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Phase II Study of Everolimus Beyond Progression

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: NCT02269670
Recruitment Status : Active, not recruiting
First Posted : October 21, 2014
Last Update Posted : October 8, 2018
Information provided by (Responsible Party):
Elisavet Paplomata, Emory University

Brief Summary:
This phase II trial studies how well everolimus and hormone therapy work in treating patients with hormone receptor positive breast cancer that has continued to spread (progressed) or returned after a period of improvement (recurred) on everolimus and exemestane hormone therapy. Everolimus is a chemotherapy drug that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen and progesterone are hormones that can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by lowering the amount of estrogen and progesterone the body makes. Giving everolimus with a different type of hormone therapy may be an effective treatment for breast cancer in patients who progressed on everolimus with exemestane.

Condition or disease Intervention/treatment Phase
Estrogen Receptor-positive Breast Cancer HER2-negative Breast Cancer Progesterone Receptor-positive Breast Cancer Recurrent Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Stage IV Breast Cancer Drug: everolimus Drug: anastrozole Drug: letrozole Drug: tamoxifen citrate Drug: fulvestrant Drug: megestrol acetate Phase 2

Detailed Description:


Progression free survival in patients with advanced or metastatic breast cancer receiving everolimus plus hormonal therapy beyond first progression.


  1. Clinical benefit rate (sum of stable disease, partial response, complete response).
  2. Response rate (partial response and complete response).
  3. Overall survival.
  4. Safety, side effects and tolerability profile of everolimus.


Patients receive everolimus orally (PO) daily and a hormone therapy regimen chosen at the discretion of the investigator (anastrozole PO daily; letrozole PO daily; tamoxifen citrate PO daily; fulvestrant intramuscularly [IM] or PO on days 1, 15, and 29, and then monthly; megestrol acetate PO 4 times daily [QID]; or other regimen). Treatment continues in the absence of disease progression or unacceptable toxicity.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Everolimus Beyond Progression in Postmenopausal Women With Advanced, Hormone Receptor Positive Breast Cancer
Study Start Date : November 2014
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: Treatment (everolimus, hormone therapy)
Patients receive everolimus PO daily and a hormone therapy regimen chosen at the discretion of the investigator (anastrozole PO daily; letrozole PO daily; tamoxifen citrate PO daily; fulvestrant IM or PO on days 1, 15, and 29, and then monthly; megestrol acetate PO QID; or other regimen). Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: everolimus
Given PO
Other Names:
  • 42-O-(2-hydroxy)ethyl rapamycin
  • Afinitor
  • RAD001

Drug: anastrozole
Given PO
Other Names:
  • ANAS
  • Arimidex
  • ICI-D1033

Drug: letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara
  • LTZ

Drug: tamoxifen citrate
Given PO
Other Names:
  • Nolvadex
  • TAM
  • tamoxifen
  • TMX

Drug: fulvestrant
Given IM or PO
Other Names:
  • Faslodex
  • ICI 182,780

Drug: megestrol acetate
Given PO
Other Names:
  • BDH 1298
  • Maygace
  • Megace
  • Megestil
  • Niagestin

Primary Outcome Measures :
  1. Response rate (partial response plus complete response) using RECIST [ Time Frame: Up to 2 years ]
    Measured at different time points, e.g. 8, 16, and 24 weeks, and will be summarized as percentage of stable disease, complete remission or partial remission along with 95% confidence interval.

  2. Progression-free survival (PFS) [ Time Frame: Up to 2 years ]
    The median PFS and survival rate at different time points for this study will be estimated by Kaplan-Meier method along with 95% confidence interval.

Secondary Outcome Measures :
  1. Clinical benefit rate (response rate plus stable disease) [ Time Frame: Up to 2 years ]
    Measured at different time points and summarized as a percentage along with 95% confidence interval.

  2. Overall survival (OS) [ Time Frame: From the initiation of alternate hormonal treatment in combination with everolimus to time of death from any cause, assessed up to 2 years ]
    The median OS and survival rate at different time points for this study will be estimated by Kaplan-Meier method along with 95% confidence interval.

  3. Incidence of adverse events assessed using Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Estrogen (ER) and/or progesterone (PR)-positive at primary diagnosis and at metastatic diagnosis where tissue is available (defined as > or = 1% of staining nuclei)
  • Progressive or recurrent breast cancer defined as disease progression or recurrence while on a combination of exemestane with everolimus
  • Human epidermal growth factor receptor 2 (HER2)/neu-negative breast cancer by standard criteria (immunohistochemistry [IHC] < 3+ or fluorescence in situ hybridization [FISH] negative if IHC 2+) at primary diagnosis
  • Histologically confirmed, measurable or evaluable disease; patients should have at least one measurable lesion; if applicable, Response Evaluation Criteria in Solid Tumors (RECIST) criteria should be used
  • Life expectancy > 6 months
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Absolute neutrophil count (ANC) > 1,500/µL
  • Platelets ≥ 100,000/µL
  • Hemoglobin > 10 g/dL
  • Creatinine ≤ 1.5 x upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 x ULN
  • International normalized ratio ≤ 1.3 (or ≤ 3 on anticoagulants)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2 x UNL unless related to primary disease
  • Signed informed consent
  • Adequate birth control
  • Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication

Exclusion Criteria:

  • Prior treatment with everolimus other than in combination with hormonal therapy for treatment of breast cancer or prior treatment with another mammalian target of rapamycin (mTOR) inhibitor (sirolimus, temsirolimus) for any indication
  • HER2 positive disease as defined by 3+ IHC or positive FISH (both in primary and metastatic sites)
  • Active infection: temperature > 100 Fahrenheit (F), fever of unknown origin, active symptoms or signs of infection as defined by the investigator
  • Uncontrolled central nervous system metastases
  • Life-threatening, visceral metastases
  • Pregnant or lactating women
  • Prior chemotherapy within the last 4 weeks
  • Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
  • Concomitant malignancies or previous malignancies within the last 5 years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix
  • History of significant cardiac disease, cardiac risk factors or uncontrolled arrhythmias
  • Hypersensitivity to trial medications (everolimus)
  • Emotional limitations, which the investigator judges could limit the patient's ability to follow up and comply with study procedures
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent
  • Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN
  • Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis
  • A known history of human immunodeficiency virus (HIV) seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of EVEROLIMUS (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients with an active, bleeding diathesis
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception; (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of EVEROLIMUS)
  • Symptomatic intrinsic lung disease or extensive tumor involvement of the lungs, resulting in dyspnea at rest
  • Taking any of the following agents:

    • Chronic treatment with systemic steroids or another immunosuppressive agent (use of steroids as part of management of everolimus toxicities will be allowed)
    • Live vaccines
    • Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; 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, bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines
    • Drugs or substances known to be inhibitors or inducers of the isoenzyme cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A)

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): NCT02269670

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United States, Georgia
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
Emory University/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States, 30342
Sponsors and Collaborators
Emory University
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Principal Investigator: Elisavet Paplomata, MD Emory University/Winship Cancer Institute

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Responsible Party: Elisavet Paplomata, Principal Investigator, Emory University Identifier: NCT02269670     History of Changes
Other Study ID Numbers: IRB00071229
NCI-2014-02092 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
WINSHIP2563-13 ( Other Identifier: Emory University/Winship Cancer Institute )
First Posted: October 21, 2014    Key Record Dates
Last Update Posted: October 8, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Megestrol Acetate
Citric Acid
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
Calcium Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Aromatase Inhibitors