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

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

  • ORG STUDY ID: J15212
  • SECONDARY ID: IRB00086616
  • NCT ID: NCT02738866

Conditions

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
PalbociclibIbrancePalbociclib and Fulvestrant
FulvestrantFaslodexPalbociclib and Fulvestrant

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, the primary objective is to 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). The study will also determine the prevalence rate of estrogen receptor α
      (ESR1) and phosphatidylinositol-3-kinase (PI3K) mutations in the study population.

      The secondary objectives include evaluating the progression-free survival (PFS) in
      participants with and without ESR1 mutations, and PI3K mutations through analysis of tumor
      biopsies and circulating plasma tumor DNA (ptDNA) samples. The study 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
      participants with hormone refractory MBC who progressed on prior palbociclib and AI. The data
      will be correlated with tumor subtypes, expression profiles, and candidate phosphoprotein
      expression with PFS in the study population.
    

Trial Arms

NameTypeDescriptionInterventions
Palbociclib and FulvestrantExperimentalParticipants 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-free survival
Time Frame:6 months
Safety Issue:
Description:To estimate progression-free survival (PFS) of palbociclib and fulvestrant in women and men with ER/PR-positive, HER2-negative MBC who progressed on a palbociclib and an AI

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • breast cancer
  • Metastatic Breast Cancer
  • palbociclib
  • fulvestrant

Last Updated

February 10, 2020