Clinical Trials /

Palbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor

NCT02738866

Description:

This study is being done to look at the role of continuing palbociclib treatment in combination with another type of hormonal therapy (fulvestrant) after disease progression of palbociclib in combination with an aromatase inhibitor.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Palbociclib</span> With <span class="go-doc-concept go-doc-intervention">Fulvestrant</span> for <span class="go-doc-concept go-doc-disease">Metastatic Breast Cancer</span> After Treatment With <span class="go-doc-concept go-doc-intervention">Palbociclib</span> and an Aromatase Inhibitor

Title

  • Brief Title: Palbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor
  • Official Title: Phase II Trial of Palbociclib With Fulvestrant in Individuals With Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer Who Have Progressed on Treatment With Palbociclib and an Aromatase Inhibitor
  • Clinical Trial IDs

    NCT ID: NCT02738866

    ORG ID: J15212

    NCI ID: IRB00086616

    Trial Conditions

    Metastatic Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Palbociclib Ibrance Palbociclib and Fulvestrant
    Fulvestrant Faslodex Palbociclib and Fulvestrant

    Trial Purpose

    This study is being done to look at the role of continuing palbociclib treatment in
    combination with another type of hormonal therapy (fulvestrant) after disease progression of
    palbociclib in combination with an aromatase inhibitor.

    Detailed Description

    In this phase II trial, we will determine the progression-free survival (PFS) of the cyclin
    dependent kinase 4/6 inhibitor (CDK4/6i) palbociclib with fulvestrant in women and men with
    estrogen or progesterone receptor (ER/PR) positive, HER2-negative metastatic breast cancer
    (MBC) who progressed on treatment with palbociclib and an aromatase inhibitor (AI). We will
    also determine the prevalence rate of estrogen receptor (ESR1) and
    phosphatidylinositol-3-kinase (PI3K) mutations in the study population.

    The secondary objectives include evaluating the progression-free survival (PFS) in patients
    with and without ESR1 mutations, and PI3K through analysis of tumor biopsies and circulating
    plasma tumor DNA (ptDNA) samples. We will also describe other alterations in genes and gene
    products relevant to the cell cycle, drug targets, tumor sensitivity and resistance, and
    identify novel protein kinases activated in biopsies from patients with hormone refractory
    MBC who progressed on prior palbociclib and AI. We will correlate tumor subtypes, expression
    profiles, and candidate phosphoprotein expression with PFS in the study population.

    Trial Arms

    Name Type Description Interventions
    Palbociclib and Fulvestrant Experimental Subjects will receive fulvestrant with palbociclib until disease progression or unacceptable toxicity. Palbociclib, Fulvestrant

    Eligibility Criteria

    Inclusion Criteria:

    - Women may be premenopausal or postmenopausal

    - Metastatic or locally advanced breast cancer, not amenable to surgery or radiation
    with curative intent

    - ER-positive and/or PR-positive, HER2-negative tumor

    - Prior treatment: progressed on and following at least 6 months of combined treatment
    with palbociclib and AI therapy; up to one (1) prior line of chemotherapy for
    advanced disease is allowed in addition to any number of prior lines of endocrine
    therapy; no prior treatment with fulvestrant, everolimus, or any agent whose
    mechanism of action is to inhibit the PI3K-mTOR pathway in the metastatic setting

    - Eastern Cooperative Oncology Group (ECOG) performance status 0-2

    - Evaluable or measurable disease

    - Disease that is amenable to biopsy

    - Adequate hematologic and renal function

    - History of central nervous system metastasis is allowed if treated and stable

    - Prior radiation therapy is allowed if recovered from toxicity and disease evaluable
    for response outside of the radiation fields or evidence of post-radiation
    progression of previously irradiated sites of disease

    - Ability to understand and willingness to sign a written informed consent document

    Exclusion Criteria:

    - Women who are pregnant or breast-feeding

    - Concurrent use of inhibitors or inducers of CYP3A4, or medications which prolong the
    QTc interval

    - Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 2
    weeks before registration; prior radiotherapy to 25% of bone marrow are not eligible
    independent of when it was received

    - Any other malignancy within 3 years prior to registration, except for adequately
    treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix

    - Any severe cardiac event within 6 months of registration

    - Prior hematopoietic stem cell or bone marrow transplantation

    - Known abnormalities in coagulation such as bleeding diathesis, or treatment with
    anticoagulants precluding intramuscular injections of fulvestrant or goserelin (if
    applicable)

    - Known or possible hypersensitivity to palbociclib, fulvestrant, goserelin (if
    applicable) or to any of their excipients

    - Known human immunodeficiency virus infection

    - Other severe acute or chronic medical or psychiatric condition, including recent or
    active suicidal ideation or behavior, or laboratory abnormality that may increase the
    risk associated with study participation or investigational product administration or
    may interfere with the interpretation of study results and, in the judgment of the
    investigator, would make the patient inappropriate for entry into this study

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival

    Prevalence of ESR1 and PI3K mutations

    Secondary Outcome Measures

    Trial Keywords

    breast cancer

    Metastatic Breast Cancer

    palbociclib

    fulvestrant