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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02738866
Recruitment Status : Active, not recruiting
First Posted : April 14, 2016
Last Update Posted : January 27, 2023
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)
Actual Enrollment : 60 participants
Allocation: N/A
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 : July 2023
Estimated Study Completion Date : December 2023

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

Information from the National Library of Medicine

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

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

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United States, District of Columbia
Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital
Washington, District of Columbia, United States, 20016
United States, Maryland
Anne Arundel Health System Research Institute, Inc.
Annapolis, Maryland, United States, 21401
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21287
United States, Pennsylvania
Allegheny Health Network (AHN) - Allegheny General Hospital ONLY
Pittsburgh, Pennsylvania, United States, 15212
Reading Hospital - McGlinn Cancer Institute
West Reading, Pennsylvania, United States, 19611
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
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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    
Other Study ID Numbers: J15212
IRB00086616 ( Other Identifier: JHMIRB )
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: January 27, 2023
Last Verified: January 2023
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
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
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