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

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Recruiting

CT.gov ID

NCT02738866

Collaborator

Pfizer (Industry)

100

Enrollment

Locations

Arm

74.2

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

100 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 :

Oct 25, 2016

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

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 Names: 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 Names: Faslodex

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 Names:

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 Names:

Faslodex

Outcome Measures

Primary Outcome Measures

Progression-free survival [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
Prevalence of ESR1 and PI3K mutations [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
2	Anne Arundel Health System Research Institute, Inc.	Annapolis	Maryland	United States	21401
3	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21287
4	Allegheny Health Network (AHN) - Allegheny General Hospital ONLY	Pittsburgh	Pennsylvania	United States	15212
5	Reading Hospital - McGlinn Cancer Institute	West Reading	Pennsylvania	United States	19611