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Clinical Trials (PDQ®)

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

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentActive18 and overPharmaceutical / IndustryPrE0102
NCT01797120

Trial Description

Summary

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.

Further Study Information

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.

Eligibility Criteria

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.

Trial Contact Information

Trial Lead Organizations/Sponsors

PrECOG, LLC

Novartis Pharmaceuticals Corporation

Noah S Kornblum, MDStudy Chair

Carolyn Andrews, RNPh: 267-207-4070
  Email: candrews@precogllc.org

Trial Sites

U.S.A.
California
  Greenbrae
 Marin Cancer Care
 Jaime Chang Ph: 415-925-5040
  Email: jchang@marinspecialtycare.com
 Bobbie Head, MDPrincipal Investigator
  Stanford
 Stanford Cancer Center
 Pei-Jen Chang Ph: 650-725-0866
  Email: peijenc@stanford.edu
 Melinda Telli, MDPrincipal Investigator
Illinois
  Rockford
 SwedishAmerican Regional Cancer Center
 Lori Kline, RN, BS, CCRP Ph: 815-489-4413
  Email: lkline@swedishamerican.org
 Harvey E Einhorn, MDPrincipal Investigator
Indiana
  Indianapolis
 Indiana University Melvin and Bren Simon Cancer Center
 Lauren Baker Ph: 317-278-5160
  Email: bakerlam@iupui.edu
 Ashley Grist Ph: 317-278-6680
  Email: acgrist@iupui.edu
 Kathy MillerPrincipal Investigator
Iowa
  Ames
 McFarland Clinic, PC
 Janet Mannetter Ph: 515-239-2621
  Email: mannetter@mgmc.com
 Joseph Merchant, MDPrincipal Investigator
Maryland
  Baltimore
 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
 Patricia Rennie Ph: 410-955-9869
  Email: prennio1@jhmi.edu
 Bridget Walsh Ph: 410-502-3613
  Email: bwalsh9@jhmi.edu
 Antonio Wolff, MDPrincipal Investigator
Michigan
  Arbor
 St. Joseph Mercy Hospital (MI Cancer Consortium)
 Melissa Case Ph: 734-712-3621
  Email: casemr@trinity-health.org
 Shannon Porter, RN Ph: 734-712-2704
  Email: porters@trinity-health.org
 Phillip Stella, MDPrincipal Investigator
Minnesota
  St. Louis Park
 Metro MN
 Betsy Wagner Ph: 952-993-1555
  Email: elizabeth.wagner@parknicollet.com
 Andrea de Jesus Ph: 952-993-3252
  Email: andrea.dejesus@parknicollet.com
 Jonathan Leach, MDPrincipal Investigator
Nebraska
  Omaha
 Missouri Valley Cancer Consortium
 Erin Smith Ph: 402-991-8070 Ext.201
  Email: esmith@mvcc.cc
 Mary Beth Wilwerding, RN Ph: 402-991-8070 Ext.202
  Email: mwilwerding@mvcc.cc
 Gamini Soori, MDPrincipal Investigator
New York
  Bronx
 Albert Einstein Cancer Center at Albert Einstein College of Medicine
 Kathy Lora Ph: 718-405-8523
  Email: klora@montefiore.org
 Karen Fehn, RN Ph: 718-405-8446
  Email: kfehn@montefiore.org
 Della Makower, MDPrincipal Investigator
  New York
 Beth Israel Medical Center - Petrie Division
 Damien Francois Ph: 212-367-1740
  Email: dfrancoi@chpnet.org
 Sherly Jacob-Perez Ph: 212-844-8292
  Email: sjacob@chpnet.org
 Paula KleinPrincipal Investigator
Ohio
  Columbus
 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
 Jennifer Sensenig Ph: 614-366-5844
  Email: Jennifer.Sensenig@osumc.edu
 Susan Ottman Ph: 614-293-0069
  Email: Susan.Ottman@osumc.edu
 Bhuvaneswari RamaswamyPrincipal Investigator
  Toledo
 Toledo COP
 Jessica Ciesler Ph: 419-843-6147 Ext.221
  Email: jciesler@tcop.info
 Joanne Lenkay Ph: 419-843-6147 Ext.228
  Email: jlenkay@tcop.info
 Rex Mowat, MDPrincipal Investigator
Pennsylvania
  Dunmore
 Hematology and Oncology Associates of Northeastern Pennsylvania
 Lee Ann Haefele Ph: 570-342-3675 Ext.218
  Email: Leeann.Haefele@hemonc1.com
 Richard Emanuelson, MDPrincipal Investigator
  Hershey
 Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
 Jo Ann Fahringer, RN, BSN Ph: 717-531-0003 Ext.285237
  Email: jfahringer@hmc.psu.edu
 Brittany Lamke Ph: 717-531-0003 Ext.289437
  Email: blamke@hmc.psu.edu
 Cristina Truica, MDPrincipal Investigator
  Philadelphia
 Fox Chase Cancer Center - Philadelphia
 Cecilia McAleer Ph: 215-728-2981
  Email: cecilia.mcaleer@fccc.edu
 Joanne Ley, RN, CCRP Ph: 215-214-1724
  Email: joanne.ley@fccc.edu
 Lori J. GoldsteinPrincipal Investigator
 Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
 Melisa Mordenti, MPH Ph: 215-955-8979
  Email: melisa.mordenti@jefferson.edu
 Nicole Napowanetz Ph: 215-503-3037
  Email: nicole.napowanetz@jefferson.edu
 Allison ZibelliPrincipal Investigator
  Pittsburgh
 UPMC Cancer Centers
 Brenda Lee Steele Ph: 412-641-2261
  Email: steelebl@upmc.edu
 Veronica Wahula Ph: 412-641-2283
  Email: wahuvf@upmc.edu
 Adam BrufskyPrincipal Investigator
  West Reading
 McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
 Christine Wolfe, RN, CCRP Ph: 484-628-8194
  Email: Christine.Wolfe@readinghealth.org
 Patricia A. Weiser, RN, CCRP Ph: 484-628-8193
  Email: Patricia.Weiser@readinghealth.org
 Terrence P. CesconPrincipal Investigator
  Wynnewood
 Main Line Heath System
 Diana Blade Ph: 484-476-2649
  Email: bladed@mlhs.org
 Sandra Lyon, RN Ph: 484-476-3494
  Email: LyonS@mlhs.org
 Paul Gilman, MDPrincipal Investigator
Texas
  Dallas
 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
 Morella Menicucci Ph: 214-590-2173
  Email: morella.menicucci@utsouthwestern.edu
 Todd Morgan Ph: 214-648-7020
  Email: todd.morgan@utsouthwestern.edu
 Barbara B. HaleyPrincipal Investigator
West Virginia
  Charleston
 Charleston Area Medical Center (CAMC)
 Augusta Kosowicz, PA-C Ph: 304-388-9940
  Email: augusta.kosowicz@camc.org
 Karen Shirey, RN Ph: 304-388-9936
  Email: karen.shirey@camc.org
 Arun Nagarajan, MDPrincipal Investigator
Wisconsin
  Green Bay
 St. Vincent Hospital Regional Cancer Center
 Jolene Cheslock Ph: 920-433-8272
  Email: jolene.cheslock@stvgb.org
 Gerald K. Bayer, MDPrincipal Investigator
  Lacrosse
 Gundersen Health System
 Deb Kettner-Sieber Ph: 608-775-1195
  Email: dlkettner@gundersenhealth.org
 Nancy Ruther Ph: 608-775-2733
  Email: nrruther@gundersenhealth.org
 Kurt Oettel, MDPrincipal Investigator
  Waukesha
 ProHealth Care Inc. (Waukesha)
 Chanda Miller Ph: 262-928-5539
  Email: Chanda.Miller@phci.org
 Timothy Wassenaar, MDPrincipal Investigator
  Wauwatosa
 Aurora Cancer Care
 Liz Sieber Ph: 414-778-4347
  Email: Elizabeth.sieber@aurora.org
 Patti Allard Ph: 414-778-4346
  Email: Patti.allard@aurora.org
 Michael Thompson, MDPrincipal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01797120
ClinicalTrials.gov processed this data on November 12, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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