Clinical trial NCT01472094: The Hurria Older PatiEnts (HOPE) With Breast Cancer Study
Official title: Clinical and Biological Predictors of Chemotherapy Toxicity in Older Adults
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Breast Cancer
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Aging (NIA)
First posted: 2011-11-16
Enrollment: 700
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Outpatient clinic practices (City of Hope, Memorial Sloan-Kettering Cancer Center, Yale University School of Medicine, University of Rochester, University of North Carolina, Wake Forest University, and Case Western Reserve University)

Brief summary: The goal of this study is to develop a "bedside to bench" model of clinical and biological predictors for toxicity to adjuvant and neoadjuvant chemotherapy in older adults with breast cancer. The investigators will develop a predictive model using clinical and biological predictors of toxicity to adjuvant and neoadjuvant chemotherapy in older adults with breast cancer. The investigators will also determine the association between clinical and biological factors and reduced relative dose intensity of the prescribed chemotherapy regimen. In addition, the investigators will explore specific chemotherapy toxicities associated with reduced relative dose intensity of a prescribed regimen.

Detailed description: Although cancer is a disease associated with aging, there is no standard tool in oncology practice that incorporates clinical and biological factors to identify older adults with cancer who may be more vulnerable to the toxicity of chemotherapy. It is generally recognized that chronological age tells relatively little about an older adult's physiological age. Oncologists allude to this when they describe an older adult as: "a 'young' 80-year-old" or "an 'old' 80-year-old," implying factors other than age contribute to the health status of an older adult. Geriatricians address this by routinely performing a "geriatric assessment," which measures independent clinical predictors of morbidity and mortality in older adults. In addition, several potential biomarkers of aging have been described that are associated with functional decline and mortality among older adults. This study will identify whether novel biomarkers of aging can predict risk of chemotherapy toxicity. The current proposal will fill this knowledge gap by melding the principles of geriatrics with those of oncology to create a tool to assess the clinical and biological risk factors for chemotherapy toxicity in older adults.

Furthermore, this study will determine the association between chemotherapy toxicity and dose reductions and/or delays that decrease chemotherapy dose intensity. Maintenance of chemotherapy dose intensity is necessary to maintain chemotherapy efficacy. Older adults are at risk for chemotherapy toxicity and if this toxicity results in decreased dose intensity, the benefits of chemotherapy will be compromised. This study will identify the association between clinical and biological predictors of grade 2-5 toxicity and relative dose intensity. Furthermore, this study will identify the specific dose-limiting toxicities. These data will provide evidence-based criteria to identify those patients whose projected risk of toxicity would limit dose intensity and compromise the efficacy of standard treatment. These data could serve as the basis for "vulnerable elderly trials" which would study an alternate therapy regimen in patients who are predicted to have a significant risk of toxicity (and compromised efficacy) with the standard regimen.

This proposal unites the fields of geriatrics and oncology, incorporating geriatric correlates of vulnerability and studying their impact in an aging oncology population. These data will be used to develop a predictive equation for the risk of chemotherapy toxicity that can be utilized in daily oncology practice. These data will facilitate decision-making regarding the risks and benefits of adjuvant chemotherapy in older adults with breast cancer and ultimately serve as a foundation on which to identify older adults at risk for chemotherapy toxicity in order to guide interventions to decrease this risk.

Eligibility criteria: Patients with Breast Cancer:

Inclusion Criteria:

* Patients with stages I-III breast cancer receiving adjuvant or neoadjuvant chemotherapy
* Able to understand English
* Able to provide informed consent
* Patients age ≥65 and of any performance status are eligible

Exclusion Criteria:

* Patients with metastatic disease

Breast Cancer Controls:

Inclusion Criteria:

* Patients with stages I-III breast cancer
* Patient will not receive adjuvant or neoadjuvant chemotherapy
* Patients age ≥65 and of any performance status are eligible
* Able to understand English
* Able to provide informed consent

Exclusion Criteria:

* Patients with metastatic disease
* Receipt of chemotherapy

Healthy Controls:

Inclusion Criteria:

* Patients age ≥65 and of any performance status are eligible
* No history of cancer (excluding non-melanoma skin cancer)
* Able to understand English
* Able to provide informed consent

Primary outcomes:
measure: Develop a predictive model of clinical and biological predictors for grade 2-5 toxicity to adjuvant and neoadjuvant chemotherapy.
timeFrame: 6 months after completion of chemotherapy
measure: Understand the association between clinical and biological factors and reduced relative dose intensity (RDI) of the prescribed chemotherapy regimen.
timeFrame: 6 months after completion of chemotherapy
measure: Identify the specific chemotherapy toxicities associated with reduced relative dose intensity of the prescribed chemotherapy regimen.
timeFrame: 6 months after completion of chemotherapy
measure: Understand the association between the receipt of adjuvant chemotherapy and change in functional status from pre-chemotherapy to end of chemotherapy.
timeFrame: 6 months after completion of chemotherapy
Secondary outcomes:
measure: Assess potential biomarkers for physiologic age, including interleukin-6, C-reactive protein, D-dimer, and p16 expression.
timeFrame: 6 months after completion of chemotherapy
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New Hyde Park
country: United States
facility: Hofstra-North-LIJ Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charlottesville
country: United States
facility: University of Virginia Health System
state: Virginia
Study officials:
affiliation: City of Hope Medical Center
name: Mina Sedrak, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S, Hansen K, Ramani R, Lachs M, Wong FL, Tew WP. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011 Sep 1;29(25):3457-65. doi: 10.1200/JCO.2011.34.7625. Epub 2011 Aug 1.
citation: Magnuson A, Sedrak MS, Gross CP, Tew WP, Klepin HD, Wildes TM, Muss HB, Dotan E, Freedman RA, O'Connor T, Dale W, Cohen HJ, Katheria V, Arsenyan A, Levi A, Kim H, Mohile S, Hurria A, Sun CL. Development and Validation of a Risk Tool for Predicting Severe Toxicity in Older Adults Receiving Chemotherapy for Early-Stage Breast Cancer. J Clin Oncol. 2021 Feb 20;39(6):608-618. doi: 10.1200/JCO.20.02063. Epub 2021 Jan 14.