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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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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

Intervention / Treatment
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* Drug: Fulvestrant
* Other: Laboratory Biomarker Analysis
* Drug: Palbociclib
* Other: Questionnaire Administration
* Drug: Aromatase Inhibitors


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (fulvestrant, palbociclib)<br>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. | Drug: Fulvestrant<br>* Given IM<br>* Other names: ZD9238;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Palbociclib<br>* Given PO<br>* Other names: PD-332991;Other: Questionnaire Administration<br>* Correlative studies<br>Drug: Aromatase Inhibitors<br>* Given PO<br>|

What is the study measuring?
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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 Karnofsky Performance Status Physician-Reported 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 |