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

• ClinicalTrials.gov Identifier: NCT02760030
• Recruitment Status: Recruiting
• First Posted: May 3, 2016
• Last Update Posted: December 20, 2019
• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Nicole Williams, Ohio State University Comprehensive Cancer Center

Study Description

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.

Condition or disease	Intervention/treatment	Phase
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	Drug: Fulvestrant; Other: Laboratory Biomarker Analysis; Drug: Palbociclib; Other: Questionnaire Administration; Drug: Aromatase Inhibitors	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 19, 2016
• Estimated Primary Completion Date: July 31, 2020
• Estimated Study Completion Date: July 31, 2020

Arms and Interventions

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.	Drug: Fulvestrant; Given IM; Other Names: Faslodex; Faslodex(ICI 182,780); ICI 182,780; ICI 182780; ZD9238; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Palbociclib; Given PO; Other Names: Ibrance; PD-0332991; PD-332991; Other: Questionnaire Administration; Correlative studies; Drug: Aromatase Inhibitors; Given PO

Outcome Measures

Primary Outcome Measures :

1. 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 [ Time Frame: 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 :

1. Change in cognition, as measured by Blessed Orientation-Memory-Concentration Test [ Time Frame: 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.
2. Change in comorbidities, as measured by the Charlson comorbidity index [ Time Frame: 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.
3. Change in depression, as measured by the Geriatric Depression Scale [ Time Frame: 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.
4. Change in functional status, as measured by the Karnofsky Performance Status Physician-Reported Scale [ Time Frame: 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.
5. Change in functional status, as measured by the History of falls [ Time Frame: 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.
6. Change in functional status, as measured by the Timed Up test [ Time Frame: 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.
7. Change in functional status, as measured by the Go Test [ Time Frame: 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.
8. Change in functional status, as measured by the Instrumental Activities of Daily Living [ Time Frame: 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.
9. Change in nutritional status, as measured by the Mini Nutritional Assessment [ Time Frame: 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.
10. Change in social activity and support, as measured by the Medical Outcome Study (MOS) [ Time Frame: 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.
11. Change in social activity and support, as measured by Social Activity Limitations Survey. [ Time Frame: 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.
12. Incidence of adverse events, using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4 [ Time Frame: 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.
13. Progression free survival [ Time Frame: Up to 1 year ]
    Calculated using Kaplan-Meier methods.
14. Progression free survival (PFS) [ Time Frame: Up to 2 years ]
    Calculated using Kaplan-Meier methods

Eligibility Criteria

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

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)

Contacts and Locations

Contacts

Contact: Ohio State University Comprehensive Cancer Center; 1-800-293-5066; OSUCCCClinicaltrials@osumc.edu

Locations

United States, Ohio

University Hopsitals Cleveland Medical Center; Recruiting

Cleveland, Ohio, United States, 44106

Contact: Cynthia Owusu, MD 216-983-3288 Cynthia.owusu@uhhospitals.org

Principal Investigator: Cynthia Owusu, MD

Ohio State University Comprehensive Cancer Center; Recruiting

Columbus, Ohio, United States, 43210

Contact: Rebekah Skerl 614-293-7243 Rebekah.Skerl@osumc.edu

Principal Investigator: Nicole Williams, MD

Sponsors and Collaborators

Ohio State University Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nicole Williams, MD; Ohio State University Comprehensive Cancer Center

More Information

Additional Information:

The Jamesline 

• Responsible Party: Nicole Williams, Principal Investigator, Ohio State University Comprehensive Cancer Center
• ClinicalTrials.gov Identifier: NCT02760030
• Other Study ID Numbers: OSU-15266; NCI-2016-00146 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); P30CA016058 ( U.S. NIH Grant/Contract )
• First Posted: May 3, 2016
• Last Update Posted: December 20, 2019
• Last Verified: December 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Fulvestrant; Palbociclib; Aromatase Inhibitors; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Estrogen Receptor Antagonists; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors