Study of Fulvestrant +/- Everolimus in Post-Menopausal, Hormone-Receptor + Metastatic Breast Ca Resistant to AI
PrE0102
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
1 other identifier
interventional
131
1 country
25
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2013
Typical duration for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 14, 2013
CompletedFirst Posted
Study publicly available on registry
February 22, 2013
CompletedStudy Start
First participant enrolled
May 31, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 22, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
September 12, 2017
CompletedResults Posted
Study results publicly available
April 30, 2018
CompletedMay 30, 2018
April 1, 2018
3.8 years
February 14, 2013
March 5, 2018
April 30, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free Survival
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. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Every 3 months until progression or up to 3 years
Secondary Outcomes (3)
Clinical Benefit Rate
Every 3 months until progression or up to 3 years
Objective Response Rate
Every 3 months until progression or up to 3 years
Overall Survival
Every 3 months until progression or up to 3 years
Study Arms (2)
Fulvestrant & Everolimus
ACTIVE COMPARATORFulvestrant 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.
Fulvestrant & Placebo
PLACEBO COMPARATORFulvestrant 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.
Interventions
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.
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.
Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.
Eligibility Criteria
You may qualify if:
- Signed informed consent.
- ≥18 years.
- ECOG Performance Status 0 or 1.
- Histologically or cytologically confirmed adenocarcinoma of the breast.
- Stage IV disease or inoperable locally advanced disease.
- ER and/or PR-positive disease. Tumors must be HER-2/neu negative or equivocal.
- Aromatase Inhibitor (AI) resistant, defined as:
- relapsed while receiving adjuvant therapy with an AI or,
- progressive disease while receiving an AI for metastatic disease
- Received one prior cycle of fulvestrant within 28 days of randomization are eligible.
- ≥2 prior doses of fulvestrant are not eligible
- Must be female and postmenopausal.
- May have received ≤1 prior systemic chemotherapy regimen for metastatic disease.
- Adequate organ function:
- Whole Blood Cells (WBC) ≥3.0 x 10⁹/L, Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L and platelet count ≥100 x 10⁹/L
- +9 more criteria
You may not qualify if:
- Major surgery or significant traumatic injury within 4 weeks of randomization or patients that may require major surgery during the course of the study.
- Investigational agents within 4 weeks of randomization.
- 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.
- Prior treatment with an mTOR inhibitor.
- Receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent ≥ 5 mg prednisone or equivalent daily.
- Receive immunization with attenuated live vaccines within one week of randomization or during the study period.
- Current or a prior history of brain metastases or leptomeningeal disease. Must not have rapidly progressive, life-threatening metastases.
- Known hypersensitivity/history of allergic reactions attributed to compounds of similar chemical or biologic composition to everolimus or fulvestrant.
- Congenital or acquired immune deficiency at increased risk of infection.
- Impairment of gastrointestinal function/disease that may significantly alter the absorption of everolimus.
- Active, bleeding diathesis.
- 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.
- Severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- PrECOG, LLC.lead
- Novartiscollaborator
Study Sites (25)
Marin Cancer Care
Greenbrae, California, 94904, United States
Stanford University
Stanford, California, 94305, United States
SwedishAmerican Regional Cancer Center
Rockford, Illinois, 61104, United States
McFarland Clinic, PC
Ames, Iowa, 50010-3014, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
St. Joseph Mercy Hospital (MI Cancer Consortium)
Ann Arbor, Michigan, 48158, United States
Metro MN
Saint Louis Park, Minnesota, 55416, United States
Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106, United States
Beth Israel
New York, New York, 10011, United States
Montefiore Medical Center
The Bronx, New York, 10466, United States
Ohio State University Medical Center
Columbus, Ohio, 43210, United States
Toledo COP
Toledo, Ohio, 43617, United States
Hematology & Oncology Associates of Northeastern PA, PC
Dunmore, Pennsylvania, 18512, United States
Penn State University
Hershey, Pennsylvania, 17033, United States
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
University of Pittsburgh- Magee Women's Hospital
Pittsburgh, Pennsylvania, 15213, United States
Reading Hospital- McGlinn Family Regional Cancer Center
West Reading, Pennsylvania, 19611, United States
Main Line Heath System
Wynnewood, Pennsylvania, 19096, United States
University of Texas Southwestern
Dallas, Texas, 75390, United States
Charleston Area Medical Center (CAMC)
Charleston, West Virginia, 25304, United States
St. Vincent Hospital
Green Bay, Wisconsin, 54301, United States
Gundersen Health System
La Crosse, Wisconsin, 54601, United States
ProHealth Care Inc. (Waukesha)
Waukesha, Wisconsin, 53188, United States
Aurora Cancer Care
Wauwatosa, Wisconsin, 53226, United States
Related Publications (1)
Kornblum N, Zhao F, Manola J, Klein P, Ramaswamy B, Brufsky A, Stella PJ, Burnette B, Telli M, Makower DF, Cheema P, Truica CI, Wolff AC, Soori GS, Haley B, Wassenaar TR, Goldstein LJ, Miller KD, Sparano JA. Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102. J Clin Oncol. 2018 Jun 1;36(16):1556-1563. doi: 10.1200/JCO.2017.76.9331. Epub 2018 Apr 17.
PMID: 29664714RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Carolyn Andrews
- Organization
- PrECOG, LLC
Study Officials
- STUDY CHAIR
Noah S Kornblum, MD
Saint Barnabas Cancer Center, Montefiore Medical Center
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 14, 2013
First Posted
February 22, 2013
Study Start
May 31, 2013
Primary Completion
March 22, 2017
Study Completion
September 12, 2017
Last Updated
May 30, 2018
Results First Posted
April 30, 2018
Record last verified: 2018-04
Data Sharing
- IPD Sharing
- Will not share
Data is proprietary.