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

NCT ID: NCT02738866

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-10-25
• Study Completion Date: 2026-06-30

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.

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.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Palbociclib and Fulvestrant

Participants will receive fulvestrant with palbociclib until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Palbociclib

Intervention Type: DRUG

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.

Fulvestrant

Intervention Type: DRUG

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).

Interventions

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.

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Ibrance; Faslodex

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
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vered Stearns, M.D.

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Jessica Tao, MD

Role: PRINCIPAL_INVESTIGATOR

SKCCC Johns Hopkins Medical Institution

Locations

Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital

Washington D.C., District of Columbia, United States

Anne Arundel Health System Research Institute, Inc.

Annapolis, Maryland, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Allegheny Health Network (AHN) - Allegheny General Hospital ONLY

Pittsburgh, Pennsylvania, United States

Reading Hospital - McGlinn Cancer Institute

West Reading, Pennsylvania, United States

Countries

United States

Other Identifiers

IRB00086616

Identifier Type: OTHER

Identifier Source: secondary_id

J15212

Identifier Type: -

Identifier Source: org_study_id