Endocrine Therapy Fulvestrant & Palbociclib or Aromatase Inhibitor Therapy in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery

Phase II Trial of Primary Endocrine Therapy With Combination of Fulvestrant or an Aromatase Inhibitor and Palbociclib in Elderly Patients With Hormone Responsive Breast Cancer Who Have Inoperable Tumor Or Operable Tumor But Cannot Undergo Surgery Due to Frailty Or Who Refuse Surgery

This phase II clinical trial studies how well fulvestrant and palbociclib works in treating older patients with breast cancer that responds to hormone treatment (hormone responsive) that cannot be removed by surgery. Estrogen can cause the growth of estrogen-receptor-positive breast cancer cells. Hormone therapy using fulvestrant may fight estrogen-receptor-positive breast cancer by blocking the use of estrogen by the tumor cells. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving fulvestrant together with palbociclib may be an effective treatment for hormone responsive breast cancer.

Study Overview

• Status: Completed
• Conditions: Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIC Breast Cancer; HER2/Neu Negative; Estrogen Receptor and/or Progesterone Receptor Positive
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Palbociclib; Drug: Fulvestrant; Other: Questionnaire Administration; Drug: Aromatase Inhibitors

Detailed Description

PRIMARY OBJECTIVES:

I. To determine treatment failure-free survival (TFFS) rate at one year of combination therapy with pure estrogen antagonist, fulvestrant and cyclin-dependent kinase (CDK) inhibitor, palbociclib as primary endocrine therapy in patients 70 years or older with newly diagnosed non-metastatic hormone receptor positive, human epidermal growth factor receptor 2 (HER-2) negative breast cancer.

SECONDARY OBJECTIVES:

I. To determine 1- and 2-year progression free survival. II. To determine safety and toxicity of this combination in the population of patients 70 years or older.

III. To determine whether longitudinal changes in geriatric assessment measures correlate with tolerability of this regimen.

OUTLINE:

Patients receive fulvestrant intramuscularly (IM) on days 1 and 15. Patients also receive palbociclib orally (PO) once daily (QD) on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 12 weeks.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • St. Elizabeth Healthcare
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western University
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Newly diagnosed invasive, estrogen receptor (ER) and/or progesterone receptor (PR)-positive, HER2 negative breast cancer; ER-and/or PR-positive breast cancer is defined by > 10% staining by immunohistochemistry
• Patients must be vulnerable or frail by Balducci Criteria or the patient is refusing breast surgery; vulnerable patients are defined as those with dependence in some instrumental activities of daily living, well controlled co-morbidities, and early symptoms of geriatric syndrome; frail patients are defined as those with three or more co-morbidities, dependence in one or more activities of daily living, or a clinically significant geriatric syndrome; geriatric syndromes include: dementia, delirium, incontinence (fecal and/or urinary), osteoporosis or spontaneous fractures, polypharmacy, visual/hearing impairment, sarcopenia and neglect or abuse
• The patient's refusal to proceed with curative breast surgery has to be documented by the surgeon's and medical oncologist's note
• Absolute neutrophil count (ANC) > 1000/uL
• Platelets > 75,000/L
• Serum creatinine 1.5 X institutional upper limit of normal (ULN)
• Total bilirubin < 1.5 X ULN
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 2.5 ULN
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Prior aromatase inhibitor therapy
• Evidence of distant metastases
• Psychiatric illness, which would prevent the patient from giving informed consent
• Patients receiving strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (fulvestrant, palbociclib); Patients receive fulvestrant IM on days 1 and 15. Patients also receive palbociclib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Palbociclib; Given PO; Other Names: Ibrance; PD-0332991; PD-332991; Drug: Fulvestrant; Given IM; Other Names: Faslodex; Faslodex(ICI 182,780); ICI 182,780; ICI 182780; ZD9238; Other: Questionnaire Administration; Correlative studies; Drug: Aromatase Inhibitors; Given PO

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment failure-free survival (TFFS) defined as the proportion of study subjects who remain on treatment from the 1st day of therapy to one year	The proportion of subjects who do not experience treatment failure at one year will be calculated along with the exact binomial confidence interval for the rate.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognition, as measured by Blessed Orientation-Memory-Concentration Test	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in comorbidities, as measured by the Charlson comorbidity index	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in depression, as measured by the Geriatric Depression Scale	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in functional status, as measured by the History of falls	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in functional status, as measured by the Timed Up test	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in functional status, as measured by the Go Test	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in functional status, as measured by the Instrumental Activities of Daily Living	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in nutritional status, as measured by the Mini Nutritional Assessment	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in social activity and support, as measured by the Medical Outcome Study (MOS)	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Change in social activity and support, as measured by Social Activity Limitations Survey.	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study
Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4	The proportion of adverse events and the exact binomial confidence interval for the rates will also be calculated.	Up to 12 weeks after removal from study
Progression free survival	Calculated using Kaplan-Meier methods.	Up to 1 year
Progression free survival (PFS)	Calculated using Kaplan-Meier methods	Up to 2 years
Change in functional status, as measured by the ECOG Performance Status Scale	Comprehensive geriatric assessment measures to assess functional independence will be summarized using descriptive statistics such as proportions with confidence intervals and means with standard deviations.	Baseline to up to 12 weeks after removal from study

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Nicole O Williams, MD, Ohio State University Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): February 16, 2017
• Primary Completion (Actual): August 31, 2025
• Study Completion (Actual): August 31, 2025

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimated): May 3, 2016

Study Record Updates

• Last Update Posted (Estimated): December 19, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Estrogen Antagonists; Pharmacologic Actions; Chemical Actions and Uses; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; Aromatase Inhibitors; palbociclib
• Other Study ID Numbers: OSU-15266; NCI-2016-00146 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No