Clinical trial NCT02760030: Endocrine Therapy Fulvestrant & Palbociclib or Aromatase Inhibitor Therapy in Treating Older Patients With Hormone Responsive Breast Cancer That Cannot Be Removed by Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
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
Lead sponsor: Ohio State University Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 14
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: 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
timeFrame: 1 year
Secondary outcomes:
measure: Change in cognition, as measured by Blessed Orientation-Memory-Concentration Test
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in comorbidities, as measured by the Charlson comorbidity index
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in depression, as measured by the Geriatric Depression Scale
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in functional status, as measured by the ECOG Performance Status Scale
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in functional status, as measured by the History of falls
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in functional status, as measured by the Timed Up test
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in functional status, as measured by the Go Test
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in functional status, as measured by the Instrumental Activities of Daily Living
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in nutritional status, as measured by the Mini Nutritional Assessment
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in social activity and support, as measured by the Medical Outcome Study (MOS)
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Change in social activity and support, as measured by Social Activity Limitations Survey.
timeFrame: Baseline to up to 12 weeks after removal from study
measure: Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4
timeFrame: Up to 12 weeks after removal from study
measure: Progression free survival
timeFrame: Up to 1 year
measure: Progression free survival (PFS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Edgewood
country: United States
facility: St. Elizabeth Healthcare
state: Kentucky
city: Cleveland
country: United States
facility: Case Western University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Ohio State University Comprehensive Cancer Center
name: Nicole O Williams, MD
role: PRINCIPAL_INVESTIGATOR
References: