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Metastatic Breast CancerPhase 2PrE0102NCT01797120

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

A Phase 2 study testing Fulvestrant and Everolimus in people with Metastatic Breast Cancer, run by PrECOG, LLC. at 25 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Fulvestrant and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
131 participants
Where
25 sitesUnited States
Study dates
31 May 2013to 12 Sep 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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
  • hemoglobin ≥9 g/dL
  • serum bilirubin ≤1.5 X ULN (Upper Limit of Normal)
  • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (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.
  • Prothrombin time (PT) with international normalized ratio (INR) ≤1.5
  • May have measurable disease, non-measurable disease, or both.
  • 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.

Who cannot join

  • 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.
Show all 22Show fewer
  • 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:
  • 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 locations and contacts

25 sites in 1 country.

25 sites in 1 country

United States25 sites
  • McFarland Clinic, PC

    Ames, Iowa, 50010-3014

  • St. Joseph Mercy Hospital (MI Cancer Consortium)

    Ann Arbor, Michigan, 48158

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Charleston Area Medical Center (CAMC)

    Charleston, West Virginia, 25304

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • Hematology & Oncology Associates of Northeastern PA, PC

    Dunmore, Pennsylvania, 18512

  • St. Vincent Hospital

    Green Bay, Wisconsin, 54301

  • Marin Cancer Care

    Greenbrae, California, 94904

  • Penn State University

    Hershey, Pennsylvania, 17033

  • Gundersen Health System

    La Crosse, Wisconsin, 54601

  • Beth Israel

    New York, New York, 10011

  • Missouri Valley Cancer Consortium

    Omaha, Nebraska, 68106

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • University of Pittsburgh- Magee Women's Hospital

    Pittsburgh, Pennsylvania, 15213

  • SwedishAmerican Regional Cancer Center

    Rockford, Illinois, 61104

  • Metro MN

    Saint Louis Park, Minnesota, 55416

  • Stanford University

    Stanford, California, 94305

  • Montefiore Medical Center

    The Bronx, New York, 10466

  • Toledo COP

    Toledo, Ohio, 43617

  • ProHealth Care Inc. (Waukesha)

    Waukesha, Wisconsin, 53188

  • Aurora Cancer Care

    Wauwatosa, Wisconsin, 53226

  • Reading Hospital- McGlinn Family Regional Cancer Center

    West Reading, Pennsylvania, 19611

  • Main Line Heath System

    Wynnewood, Pennsylvania, 19096

Other trials in United States

About this study

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

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.

Read more

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.

Read the 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 (yes vs. no), and prior chemotherapy for metastatic disease (yes vs. no).

Patients will be evaluated for disease response every 12 weeks, and treated until disease progression or unacceptable toxicity or withdrawal of consent for a maximum of 12 cycles (48 weeks).

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.

Being tested
Fulvestrant, Everolimus, Placebo
Keywords
Post-Menopausal Patients, Hormone-Receptor Positive, Resistant to Aromatase Inhibitor Therapy, Fulvestrant, Faslodex, mTOR Inhibitor, Everolimus, RAD001, Afinitor
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FulvestrantDrug

    Also called Faslodex

    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.

  • EverolimusDrug

    Also called mTOR Inhibitor, RAD001, Afinitor

    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.

  • PlaceboDrug

    Also called Sugar Pill

    Placebo for Everolimus (2 tablets) daily x 12 cycles. Placebo manufactured to mimic everolimus tablet.

Study groups in NCT01797120
Study groupRoleWhat they receive
Fulvestrant & EverolimusActive 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.
Receives: Drug: Fulvestrant; Drug: Everolimus
Fulvestrant & PlaceboPlacebo 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.
Receives: Drug: Fulvestrant; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Every 3 months until progression or up to 3 years

Secondary outcomes (3)
  1. Clinical Benefit Rate

    Clinical benefit rate is defined as number of patients with objective response (complete response or partial response) or stable disease for at least 24 weeks divided by number of patients randomized in each arm. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease; Complete Response (CR) is defined as disappearance of all target lesions.

    Measured: Every 3 months until progression or up to 3 years

  2. Objective Response Rate

    Objective response rate is defined as number of patients with complete or partial response (by Physical Exam, CT or MRI) divided by number of patients randomized in each arm

    Measured: Every 3 months until progression or up to 3 years

  3. Overall Survival

    Overall survival will be characterized using Kaplan-Meier plots and other descriptive metrics.

    Measured: Every 3 months until progression or up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2013 (estimated)
  2. Study start31 May 2013
  3. Primary completion22 Mar 2017
  4. Study completion12 Sep 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
131 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01797120
Sponsor's protocol ID
PrE0102
Acronym
PrE0102
Status last verified
Apr 2018
First submitted
14 Feb 2013
Last updated
30 May 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Data is proprietary.

Publications

  • 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.

    PubMed 29664714

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fulvestrant and Everolimus in people with Metastatic Breast Cancer, run by PrECOG, LLC. at 25 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (time frame: Every 3 months until progression or up to 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01797120, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 May 2018.

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