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

Johns Hopkins Medicine

Status and phase

Active, not recruiting

Phase 2

Conditions

Metastatic Breast Cancer

Treatments

Drug: Palbociclib

Drug: Fulvestrant

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02738866

IRB00086616 (Other Identifier)

J15212

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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