Study of Fulvestrant +/- Everolimus in Post-Menopausal, Hormone-Receptor + Metastatic Breast Ca Resistant to AI (PrE0102)

This study is currently recruiting participants.
Verified January 2014 by PrECOG, LLC.
Information provided by (Responsible Party):
PrECOG, LLC. Identifier:
First received: February 14, 2013
Last updated: January 6, 2014
Last verified: January 2014

Post-menopausal women with hormone-receptor positive (HR+) metastatic breast cancer resistant to aromatase inhibitor (AI) therapy will be randomized to receive Fulvestrant (Faslodex) with Everolimus or Fulvestrant (Faslodex) with a placebo (no active ingredients).

Fulvestrant has demonstrated activity when used as first, second, or third line endocrine therapy, making it an attractive therapy for combination with other agents. In addition, it is commonly reserved for use following disease progression on AI therapy.

Everolimus is an orally administered drug that blocks a signaling pathway called "mTOR". "mTOR" acts as a regulator for many processes in the body, including cell growth. Blocking this pathway may have an effect on cell growth.

The combination of a novel class of agents (mTOR inhibitors) and an established standard treatment for metastatic HR+ breast cancer may potentially increase the clinical benefit by targeting multiple different biological pathways.

Condition Intervention Phase
Metastatic Breast Cancer
Drug: Fulvestrant
Drug: Everolimus
Drug: Placebo (for Everolimus)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-Blind, Placebo-Controlled Phase II Trial of Fulvestrant (Faslodex) Plus Everolimus in Post-Menopausal Patients With Hormone-Receptor Positive Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy

Resource links provided by NLM:

Further study details as provided by PrECOG, LLC.:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: Every 3 months until progression or up to 3 years ] [ Designated as safety issue: No ]
    Progression-free survival documented by Physical Exam, CT Scan or MRI in post-menopausal patients with hormone-receptor positive metastatic breast cancer that is resistant to aromatase inhibitor therapy treated with fulvestrant and everolimus compared to fulvestrant alone from randomization to documented disease progression or death.

Secondary Outcome Measures:
  • Participant Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Monthly up to 3 years ] [ Designated as safety issue: Yes ]
    Comparison of overall toxicity and of grade 3-4 toxicity in the combination arm and the fulvestrant arm.

  • Objective Response Rate [ Time Frame: Every 3 months until progression or up to 3 years ] [ Designated as safety issue: No ]
    Objective response rates (by Physical Exam, CT or MRI) will be provided for each arm.

  • Time to Progression [ Time Frame: Every 3 months until progression or up to 3 years ] [ Designated as safety issue: No ]
    Median time to progression (by Physical Exam, CT or MRI) will be estimated for each arm.

  • Overall Survival [ Time Frame: Every 3 months until progression or up to 3 years ] [ Designated as safety issue: No ]
    Overall survival will be characterized using Kaplan-Meier plots and other descriptive metrics.

Estimated Enrollment: 130
Study Start Date: May 2013
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fulvestrant & Everolimus
Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus everolimus daily x 12 cycles.
Drug: Fulvestrant

Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Other Name: Faslodex
Drug: Everolimus

Everolimus 10 mg (2 tablets) daily x 12 cycles.

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Other Names:
  • mTOR Inhibitor
  • RAD001
  • Afinitor
Placebo Comparator: Fulvestrant & Placebo
Fulvestrant Day 1 & 15 of Cycle 1, then Day 1 of all subsequent cycles (every 28 days for 12 cycles) plus placebo daily x 12 cycles.
Drug: Fulvestrant

Fulvestrant 500 mg Day 1 & 15 of Cycle 1, then 500 mg Day 1 of all subsequent cycles (every 28 days for 12 cycles).

If no evidence of disease progression after 12 cycles, unblind and continue same dose and schedule until progression or unacceptable toxicity.

Other Name: Faslodex
Drug: Placebo (for Everolimus)
Placebo (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.
Other Name: Sugar Pill

Detailed Description:

Breast cancer is the most commonly diagnosed malignancy in women worldwide. In the United States, an estimated 230,480 new cases of invasive breast cancer were diagnosed in 2011, with 39,520 breast cancer deaths. In 40-80% of women with node-positive disease at diagnosis, their breast cancer will recur. When distant metastases occur, median survival is 18 to 36 months from time of recurrence. Among the 60-70% of women with HR+ breast cancer, 40-60% of them will benefit from endocrine therapy. Endocrine therapy has shown to yield similar survival rates in hormone-sensitive disease as compared to chemotherapy; although response rates are lower and responses develop more slowly. Endocrine therapy is considerably less toxic than chemotherapy, and is therefore the preferred treatment option for patients with HR+ disease.

Endocrine therapy represents the foundation of treatment for HR+ metastatic and locally advanced breast cancer. Multiple compounds in varying classes exist, and those most widely used include the selective estrogen receptor modulators (SERMs), aromatase inhibitors (AIs), and the selective estrogen receptor down-regulators (SERDs). Although the utility of these drugs is well established, as many as 50% of women with HR+ breast cancer will fail to respond to endocrine treatment. Moreover, those who do respond will inevitably develop acquired resistance.

Fulvestrant is the first drug which acts as a pure estrogen receptor (ER) antagonist without known agonist effects. It competitively binds to the ERs with an approximately 100 times greater affinity than that of tamoxifen. Fulvestrant promotes the degradation of ERs and subsequently prevents ER-mediated gene transcription.

Everolimus (RAD001) is an oral derivative of rapamycin that is an m-TOR inhibitor. At cellular and molecular levels, everolimus acts as a signal transduction inhibitor. Everolimus selectively inhibits mTOR (mammalian target of rapamycin); a key and highly conserved serine-threonine kinase which is present in all cells and is a central regulator of protein synthesis and ultimately cell growth, cell proliferation, angiogenesis and cell survival. mTOR is the only currently known target of everolimus.

In oncology, everolimus has been in clinical development since 2002 for patients with various hematologic and non-hematologic malignancies as a single agent or in combination with antitumor agents, including cytotoxic chemotherapeutic agents, targeted therapies, antibodies and hormonal agents.

Patients will be randomized (1:1) to receive everolimus or placebo with fulvestrant after consideration of stratification factors of performance status (0 vs. 1), measurable disease (with or without non-measurable) vs. non-measurable disease, and prior chemotherapy for metastatic disease vs. no prior chemotherapy.

Patients will be evaluated for disease response every 12 weeks and treated until disease progression or unacceptable toxicity for a total of 12 cycles.

Patients with no evidence of progressive disease who remain on study after completing 12 cycles are unblinded and continue to receive fulvestrant alone (if originally randomized to placebo) or in combination with everolimus (if originally randomized to everolimus) at the same dose and schedule. Patients will continue to be evaluated for disease response every 12 weeks and continue until disease progression or unacceptable toxicity.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Signed informed consent.
  2. ≥18 years.
  3. ECOG Performance Status 0 or 1.
  4. Histologically or cytologically confirmed adenocarcinoma of the breast.
  5. Stage IV disease or inoperable locally advanced disease.
  6. ER and/or PR-positive disease. Tumors must be HER-2/neu negative or equivocal.
  7. Aromatase Inhibitor (AI) resistant, defined as:

    • relapsed while receiving adjuvant therapy with an AI or,
    • progressive disease while receiving an AI for metastatic disease
  8. Received one prior dose of fulvestrant within 28 days of randomization are eligible.

    • ≥2 prior doses of fulvestrant are not eligible
  9. Must be female and postmenopausal.
  10. May have received ≤1 prior systemic chemotherapy regimen for metastatic disease.
  11. Adequate organ function:

    • WBC ≥3.0 x 10⁹/L, ANC ≥1.5 x 10⁹/L and platelet count ≥100 x 10⁹/L
    • hemoglobin ≥9 g/dL
    • serum bilirubin ≤1.5 X ULN (Upper Limit of Normal)
    • AST or ALT ≤2.5 X ULN (≤5 x ULN in patients with liver metastases)
    • serum creatinine ≤1.5 X ULN
    • serum albumin ≥3 g/dL
    • fasting serum cholesterol ≤300 mg/dL OR ≤7.75 mmol/L AND fasting triglycerides ≤2.5 x ULN.
    • PT with INR ≤1.5
  12. May have measurable disease, non-measurable disease, or both.
  13. Basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix within the past five years treated with curative intent. History of prior malignancy are eligible if disease-free for >3 years.

Exclusion Criteria:

  1. Major surgery or significant traumatic injury within 4 weeks of randomization or patients that may require major surgery during the course of the study.
  2. Investigational agents within 4 weeks of randomization.
  3. Anticancer treatment within 4 weeks of randomization, with the following exceptions:

    • Bisphosphonates or Zometa for bone metastases
    • a GnRH analog is permitted if the patient had progressive disease on a GnRH (Gonadotropin-Releasing Hormone) analog plus a SERM (Selective Estrogen Receptor Modulators) or an AI; the GnRH analog may continue but the SERM or AI must be discontinued.
  4. Prior treatment with an mTOR inhibitor.
  5. Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent ≥ 5 mg prednisone or equivalent daily.
  6. Receive immunization with attenuated live vaccines within one week of randomization or during the study period.
  7. Current or a prior history of brain metastases or leptomeningeal disease. Must not have rapidly progressive, life-threatening metastases.
  8. Known hypersensitivity/history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or fulvestrant.
  9. Congenital or acquired immune deficiency at increased risk of infection.
  10. Impairment of gastrointestinal function/disease that may significantly alter the absorption of everolimus.
  11. Active, bleeding diathesis.
  12. History of any condition or uncontrolled intercurrent illness that in the opinion of the local investigator might interfere with or limit the patient's ability to comply with the protocol or pose additional or unacceptable risk to the patient.
  13. Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:

    • Symptomatic congestive heart failure of New York Heart Association Class III or IV
    • Unstable angina pectoris, myocardial infarction within 6 months of randomization, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
    • History of symptomatic pulmonary disease or non-malignant pulmonary disease requiring treatment.
    • Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN
    • Active (acute or chronic) or uncontrolled severe infections
    • Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh Class C).

Note: Detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening.

  Contacts and Locations
Please refer to this study by its identifier: NCT01797120

Contact: Carolyn Andrews, RN 267-207-4070

United States, California
Marin Cancer Care Recruiting
Greenbrae, California, United States, 94904
Contact: Jaime Chang    415-925-5040   
Principal Investigator: Bobbie Head, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Pei-Jen Chang    650-725-0866   
Principal Investigator: Melinda Telli, MD         
United States, Illinois
SwedishAmerican Regional Cancer Center Recruiting
Rockford, Illinois, United States, 61104
Contact: Lori Kline, RN, BS, CCRP    815-489-4413   
Principal Investigator: Harvey E Einhorn, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Lauren Baker    317-278-5160   
Contact: Ashley Grist    317-278-6680   
Principal Investigator: Kathy Miller, MD         
United States, Iowa
McFarland Clinic, PC Recruiting
Ames, Iowa, United States, 50010-3014
Contact: Janet Mannetter    515-239-2621   
Principal Investigator: Joseph Merchant, MD         
United States, Michigan
St. Joseph Mercy Hospital (MI Cancer Consortium) Recruiting
Arbor, Michigan, United States, 48158
Contact: Melissa Case    734-712-3621   
Contact: Shannon Porter, RN    734-712-2704   
Principal Investigator: Phillip Stella, MD         
United States, Minnesota
Metro MN Recruiting
St. Louis Park, Minnesota, United States, 55416
Contact: Betsy Wagner    952-993-1555   
Contact: Andrea de Jesus    952-993-3252   
Principal Investigator: Jonathan Leach, MD         
United States, Nebraska
Missouri Valley Cancer Consortium Recruiting
Omaha, Nebraska, United States, 68106
Contact: Erin Smith    402-991-8070 ext 201   
Contact: Mary Beth Wilwerding, RN    402-991-8070 ext 202   
Principal Investigator: Gamini Soori, MD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10466
Contact: Kathy Lora    718-405-8523   
Contact: Karen Fehn, RN    718-405-8446   
Principal Investigator: Della Makower, MD         
Beth Israel Recruiting
New York, New York, United States, 10011
Contact: Damien Francois    212-367-1740   
Contact: Sherly Jacob-Perez    212-844-8292   
Principal Investigator: Paula Klein, MD         
United States, Ohio
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Jennifer Sensenig    614-366-5844   
Contact: Susan Ottman    614-293-0069   
Principal Investigator: Bhuvaneswari Ramaswamy, MD         
Toledo COP Recruiting
Toledo, Ohio, United States, 43617
Contact: Jessica Ciesler    419-843-6147 ext 221   
Contact: Joanne Lenkay    419-843-6147 ext 228   
Principal Investigator: Rex Mowat, MD         
United States, Pennsylvania
Hematology & Oncology Associates of Northeastern PA, PC Recruiting
Dunmore, Pennsylvania, United States, 18512
Contact: Lee Ann Haefele    570-342-3675 ext 218   
Principal Investigator: Richard Emanuelson, MD         
Penn State University Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Jo Ann Fahringer, RN, BSN    717-531-0003 ext 285237   
Contact: Brittany Lamke    717-531-0003 ext 289437   
Principal Investigator: Cristina Truica, MD         
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Melisa Mordenti, MPH    215-955-8979   
Contact: Nicole Napowanetz    215-503-3037   
Principal Investigator: Allison Zibelli, MD         
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Cecilia McAleer    215-728-2981   
Contact: Joanne Ley, RN, CCRP    215-214-1724   
Principal Investigator: Lori Goldstein, MD         
University of Pittsburgh- Magee Women's Hospital Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Brenda Lee Steele    412-641-2261   
Contact: Veronica Wahula    412-641-2283   
Principal Investigator: Adam Brufsky, MD         
Reading Hospital- McGlinn Family Regional Cancer Center Recruiting
West Reading, Pennsylvania, United States, 19611
Contact: Christine Wolfe, RN, CCRP    484-628-8194   
Contact: Patricia A. Weiser, RN, CCRP    484-628-8193   
Principal Investigator: Terrence Cescon, MD         
Main Line Heath System Recruiting
Wynnewood, Pennsylvania, United States, 19096
Contact: Diana Blade    484-476-2649   
Contact: Sandra Lyon, RN    484-476-3494   
Principal Investigator: Paul Gilman, MD         
United States, West Virginia
Charleston Area Medical Center (CAMC) Recruiting
Charleston, West Virginia, United States, 25304
Contact: Augusta Kosowicz, PA-C    304-388-9940   
Contact: Karen Shirey, RN    304-388-9936   
Principal Investigator: Arun Nagarajan, MD         
United States, Wisconsin
St. Vincent Hospital Recruiting
Green Bay, Wisconsin, United States, 54301
Contact: Jolene Cheslock    920-433-8272   
Principal Investigator: Gerald K. Bayer, MD         
Gundersen Health System Recruiting
Lacrosse, Wisconsin, United States, 54601
Contact: Deb Kettner-Sieber    608-775-1195   
Contact: Nancy Ruther    608-775-2733   
Principal Investigator: Kurt Oettel, MD         
ProHealth Care Inc. (Waukesha) Recruiting
Waukesha, Wisconsin, United States, 53188
Contact: Chanda Miller    262-928-5539   
Principal Investigator: Timothy Wassenaar, MD         
Aurora Cancer Care Recruiting
Wauwatosa, Wisconsin, United States, 53226
Contact: Liz Sieber    414-778-4347   
Contact: Patti Allard    414-778-4346   
Principal Investigator: Michael Thompson, MD         
Sponsors and Collaborators
Study Chair: Noah S Kornblum, MD Saint Barnabas Cancer Center, Montefiore Medical Center
  More Information

Responsible Party: PrECOG, LLC. Identifier: NCT01797120     History of Changes
Other Study ID Numbers: PrE0102
Study First Received: February 14, 2013
Last Updated: January 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by PrECOG, LLC.:
Post-Menopausal Patients
Hormone-Receptor Positive
Resistant to Aromatase Inhibitor Therapy
mTOR Inhibitor

Additional relevant MeSH terms:
Hormones, Hormone Substitutes, and Hormone Antagonists
Hormone Antagonists
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Estrogen Antagonists
Estrogen Receptor Modulators
Antineoplastic Agents, Hormonal
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on April 23, 2014