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

Phase 2

Active, not recruiting

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

• Registration Number: NCT02760030
• Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2016-03-29
• Study First Submitted QC: 2016-04-29
• Study First Posted: 2016-05-03
• Study Start: 2017-02-16
• Status Verified: 2024-12
• Last Update Submitted: 2025-02-10
• Last Update Posted: 2025-02-12
• Primary Completion: 2025-07-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Female
• Target Recruitment: 14

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (fulvestrant, palbociclib)	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.
Treatment (fulvestrant, palbociclib)	Questionnaire Administration	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.
Treatment (fulvestrant, palbociclib)	Aromatase Inhibitors	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.
Treatment (fulvestrant, palbociclib)	Laboratory Biomarker Analysis	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.
Treatment (fulvestrant, palbociclib)	Fulvestrant	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.

Primary Outcome Measures

Name	Time	Method
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	1 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.

Secondary Outcome Measures

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

Trial Locations

Locations (3)

St. Elizabeth Healthcare; 🇺🇸 Edgewood, Kentucky, United States

Case Western University; 🇺🇸 Cleveland, Ohio, United States

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States