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

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ClinicalTrials.gov Identifier: NCT02738866
Recruitment Status : Recruiting
First Posted : April 14, 2016
Last Update Posted : February 7, 2019
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Drug: Palbociclib Drug: Fulvestrant Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 25, 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Palbociclib and Fulvestrant
Participants will receive fulvestrant with palbociclib until disease progression or unacceptable toxicity.
Drug: Palbociclib
Palbociclib will be given orally, continued at the same dose as was received previously; the maximum starting dose will be per the approved label, a dose of 125 mg once daily. Palbociclib will be taken days 1-21, then seven days off treatment to complete one 28 day cycle.
Other Name: Ibrance

Drug: Fulvestrant
Fulvestrant 500 mg should be administered intramuscularly into the buttocks slowly (1-2 minutes per injection) as two 5 mL injections, one in each buttock, on days 1, 15, and 29 (i.e., Cycle 2 Day 1) and once monthly thereafter (i.e., day 1 of each cycle).
Other Name: Faslodex




Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 6 months ]
    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

  2. Prevalence of ESR1 and PI3K mutations [ Time Frame: 6 months ]
    To determine the prevalence of ESR1 and PI3K mutations in tissue and in ptDNA in women and men with ER/PR-positive, HER2-negative MBC who progressed on a palbociclib and an AI



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02738866


Contacts
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Contact: Hopkins Breast Trials 410-614-1361 HopkinsBreastTrials@jhmi.edu
Contact: Kimmel Cancer Center Clinical Research Office 410-955-8866 jhcccro@jhmi.edu

Locations
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United States, District of Columbia
Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital Recruiting
Washington, District of Columbia, United States, 20016
Contact: Hopkins Breast Trials    410-955-8804    HopkinsBreastTrials@jhmi.edu   
Principal Investigator: Raquel Nunes, MD         
United States, Maryland
Anne Arundel Health System Research Institute, Inc. Recruiting
Annapolis, Maryland, United States, 21401
Principal Investigator: Jeanine Werner, MD         
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21287
Contact: Hopkins Breast Trials    410-955-8804    HopkinsBreastTrials@jhmi.edu   
Principal Investigator: Vered Stearns, M.D.         
United States, Pennsylvania
Allegheny Health Network (AHN) - Allegheny General Hospital ONLY Recruiting
Pittsburgh, Pennsylvania, United States, 15212
Principal Investigator: Antonios Christou, MD         
Reading Hospital - McGlinn Cancer Institute Recruiting
West Reading, Pennsylvania, United States, 19611
Principal Investigator: Terrence Cescon, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Pfizer
Investigators
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Study Chair: Vered Stearns, M.D. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02738866     History of Changes
Other Study ID Numbers: J15212
IRB00086616 ( Other Identifier: JHMIRB )
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: February 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to make individual participant data available.

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
breast cancer
Metastatic Breast Cancer
palbociclib
fulvestrant

Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Palbociclib
Aromatase Inhibitors
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors