Palbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor
Primary Purpose
Metastatic Breast Cancer
Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Palbociclib
Fulvestrant
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring breast cancer, Metastatic Breast Cancer, palbociclib, fulvestrant
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
Sites / Locations
- Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital
- Anne Arundel Health System Research Institute, Inc.
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
- Allegheny Health Network (AHN) - Allegheny General Hospital ONLY
- Reading Hospital - McGlinn Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Palbociclib and Fulvestrant
Arm Description
Participants will receive fulvestrant with palbociclib until disease progression or unacceptable toxicity.
Outcomes
Primary Outcome Measures
Progression-free survival
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
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
Secondary Outcome Measures
Full Information
NCT ID
NCT02738866
First Posted
April 11, 2016
Last Updated
August 3, 2023
Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT02738866
Brief Title
Palbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
October 25, 2016 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators
Pfizer
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer
Keywords
breast cancer, Metastatic Breast Cancer, palbociclib, fulvestrant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Palbociclib and Fulvestrant
Arm Type
Experimental
Arm Description
Participants will receive fulvestrant with palbociclib until disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
Palbociclib
Other Intervention Name(s)
Ibrance
Intervention Description
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
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
Faslodex
Intervention Description
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).
Primary Outcome Measure Information:
Title
Progression-free survival
Description
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
Time Frame
6 months
Title
Prevalence of ESR1 and PI3K mutations
Description
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
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vered Stearns, M.D.
Organizational Affiliation
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Official's Role
Study Chair
Facility Information:
Facility Name
Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20016
Country
United States
Facility Name
Anne Arundel Health System Research Institute, Inc.
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Allegheny Health Network (AHN) - Allegheny General Hospital ONLY
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Reading Hospital - McGlinn Cancer Institute
City
West Reading
State/Province
Pennsylvania
ZIP/Postal Code
19611
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to make individual participant data available.
Learn more about this trial
Palbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor
We'll reach out to this number within 24 hrs