Older Breast Cancer Patients: Risk for Cognitive Decline

Cognitive Decline Clinical Trial

— TLC  

Official title:

Older Breast Cancer Patients: Risk for Cognitive Decline. The Thinking and Living With Cancer (TLC) Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03451383
• Other study ID #: 2008-363
• Status: Recruiting
• Start date: August 1, 2010
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2023
• Source: Georgetown University
• Contact: Jeanne Mandelblatt
• Phone: 2026870801
• Email: mandelbj[@]georgetown.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this study is to evaluate the impact of systemic therapy on cognition in older breast cancer patients, explore change in APE, LM and Cognition domains, measure associations between cognitive decline and QOL, and describe how genetic polymorphisms, inflammatory biomarkers, sleep and physical measures moderate cognitive outcomes. This study is being done nationally, with recruiting sites at Georgetown University, Montgomery General Hospital, Virginia Cancer Specialists, Washington Hospital Center, Reston Breast Care Specialists, Memorial Sloan-Kettering, Moffitt Cancer Center, City of Hope National Medical Center, Hackensack University Medical Center, Indiana University and University of California, Los Angeles.

Description:

Cancer is the leading cause of death in the US and breast cancer is the second most common cancer among women in our country. Older women (women 60 and older) presently account for nearly half of all new cases of breast cancer. With the "graying of America" and advances in treatment for breast cancer, the absolute number of older women undergoing breast cancer treatment and surviving their disease will almost double by the year 2030. Systemic hormonal and non-hormonal chemotherapy is credited with improvements in survival, and rates of use of these modalities have increased substantially over the past two decades. Preliminary work has found that older women are interested in chemotherapy even for small returns in survival extension. However, cognitive impairment has been demonstrated in most studies of breast cancer systemic treatments, but virtually all of this research has been conducted in younger populations. Since aging itself is associated with cognitive declines, it seems very likely that older women are particularly vulnerable to the adverse cognitive effects of systemic therapy; our preliminary work strongly suggests that this is the case, but this has never been empirically tested.

This study will be the first large-scale, prospective, controlled investigation to evaluate cognitive changes in older cancer patients and it will provide the basis for the next generation of mechanistic, treatment and intervention studies. These will be important since data from younger patients cannot be directly translated into the older population. Investigators will use the vulnerability model of cancer survivorship to prospectively describe the magnitude of systemic therapy effects on cognition in older (age >60 years) breast cancer patients over a 60 month period, explore change in APE, LM and Cognition domains, test associations between cognition and quality of life (QOL), and evaluate whether genetic polymorphisms, inflammatory biomarkers, sleep and physical measures moderate cognitive outcomes.

To achieve these objectives, investigators have assembled a multi-disciplinary team of oncologists, geriatricians, neurologists, neuro- and cognitive psychologists, behavioral scientists and consumers from Lombardi Comprehensive Cancer Center (LCCC), Memorial Sloan-Kettering Cancer Center (MSKCC), Moffitt Cancer Center, City of Hope National Medical Center (COH), Hackensack University Medical Center (HUMC), Indiana University (IU), Boston University (BU), University of California (UCLA), University of South Florida (USF) and their satellites, will work together to prospectively enroll 850 newly diagnosed older breast cancer cases from LCCC, MSKCC, Moffitt, COH, HUMC, IU and tertiary referral centers with high volumes. An equal number of non-cancer friend controls will be recruited. Friend controls were chosen since they will be similar to patients in most ways except for exposure to cancer and its treatments and they should be motivated to participate. If friends are not available, controls matched to cases on age, education, race, and area (DC/NY/FL/CA/NJ/IU) will be recruited from the community.

Investigators will administer baseline neuropsychological testing prior to any systemic treatment (or at enrollment for controls), survey women about subjective cognitive function, sleep, psychosocial factors, QOL and activities of daily living (IADLS). Subjects will take part in physical measurements, including grip strength, sit to stand and walk speed tests. Investigators will abstract clinical data from medical records. Investigators will obtain blood or saliva to test for APOE, COMT and other genetic polymorphisms at enrollment; these results will not be provided to participants since this is considered a research test). Subjects have the option to provide blood for biomarker research and for biobanking. Subjects will also provide one week of sleep monitoring. Subjects at IU will have the option to participate in neuroimaging. Investigators conduct follow-up interviews and repeat the neuropsychological testing, physical measures, blood/saliva collection, sleep monitoring and optional neuroimaging 12 months after baseline assessment; this time point corresponds to 3-6 months post-treatment among women who receive chemotherapy. Our primary cognitive outcome will be change in summary score on tests in the Attention, Processing Speed, and Executive Function domain, Learning and Memory domain, and Subjective Cognition domain. In secondary analyses, investigators examine changes in scores on additional domains to assess broader cognitive function and examine questions of differential impact.

Data from this study will guide future interventions to better select older women for whom the benefits of systemic therapy outweigh the harms and to develop approaches to mitigate negative consequences of systemic treatment when it is indicated, improving the quality of care for the growing population of older breast cancer patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1700
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 60 Years to 105 Years

Eligibility

Inclusion Criteria:

For cancer patients, eligibility includes:

• being female

• Age 60+ at diagnosis of a new primary histological confirmed adenocarcinoma breast cancer

• AJCC stages 0-3 or planning neoadjuvant therapy

• In the judgment of the consenting professional, able to communicate well enough in English through verbal and written communication to complete the study assessments and provide informed consent

• If currently taking psychoactive medications (including, but not limited to anticonvulsants, antidepressants, and anxiolytics), dose must have been stable at least two months prior to enrollment.

• Participant report of no previous or current chemotherapy or hormonal treatment use (anastrazole, exemestane, etc.) This does not include hormonal replacement therapy, synthetic thyroid hormones, etc.

For controls, eligibility includes:

• being female

• Age 60+

• In the judgment of the consenting professional, able to communicate well enough in English through verbal and written communication to complete the study assessments and provide informed consent

• If currently taking psychoactive medications (including, but not limited to anticonvulsants, antidepressants, and anxiolytics), dose must have been stable at least two months prior to enrollment.

Exclusion:

We apply the same exclusion criteria for patients and controls.

• Participant report of a history of formal diagnosis of neurological problems (i.e. Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Dementia, Seizure Disorders, brain tumors, etc.)

• Participant report of surgery on the brain for any reason (cancerous or non-cancerous tumors, subdural hematomas, AV malformations, increased intracranial pressure, etc.)

• Participant report of a history of stroke (with the exception of TIA if =1 year ago)

• Participant report of HIV/AIDS

• Participant report of moderate to severe head trauma (loss of consciousness > 60 min or with evidence of structural brain changes on imaging)

• History of major psychiatric disorder (DSM-IV Axis 1) (i.e. major depressive disorder (untreated or poorly treated), bipolar disorders, schizophrenia, or substance abuse disorders (self-reported and/or stated in medical record).

• Participant report of a history of prior breast or other cancer with the exception of non-melanoma skin cancer. An exception for cases only: women who completed treatment for a previous cancer at least 5 years ago and have not undergone any chemotherapy or hormonal therapy. This previous cancer cannot be breast cancer.

• Participant report of previous or current chemotherapy or hormonal therapy use

• Participant use of methotrexate (Amethopterin, Rhematrex, Trexall) or rituximab (Rituxin) for rheumatoid arthritis, psoriasis or Crohn's disease, or cyclophosphamide (Cytoxan, Neosar) for Lupus.

• Visual or hearing impairment that would preclude ability to complete interviews or neuropsychological testing, such as significant macular degeneration or being unable to correct hearing with hearing aides

• Non-English speaking

• To participate in the optional neuroimaging portion of the study:

Participant cannot be claustrophobic Participant cannot have a pacemaker, aneurysm clip or other implants that are not MRI safe Participant cannot have any type of implanted electrical device

Related Conditions & MeSH terms

• Age-related Cognitive Decline
• Breast Neoplasms
• Cancer, Breast
• Cognitive Decline
• Cognitive Dysfunction

Locations

Country	Name	City	State
United States	Georgetown University	Washington	District of Columbia

Sponsors (6)

Lead Sponsor	Collaborator
Georgetown University	City of Hope Medical Center, H. Lee Moffitt Cancer Center and Research Institute, Hackensack Meridian Health, Indiana University, Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Attention, Processing Speed, Executive Function (APE) Domain	Using neuropsychological tests: NAB Digits Forward and Backward, Trailmaking A and B, Digit Symbol Subtest-Wechsler Adult, The Timed Instrumental Activities of Daily Living, Controlled Oral Word Association Test, NAB Driving Scenes and NAB Figure Drawing. These measures are aggregated to arrive at one reported value. The individual tests are first selected via factor analysis, then the selected raw scores are standardized to baseline controls by age and education group. The final domain score is calculated by averaging available individual z-standardized test scores.	Baseline and annually up to 5 years
Primary	Change in Learning and Memory (LM) Domain	Using neuropsychological tests: Logical Memory I and II (Wechsler Memory Scale), NAB List Learning (Immediate Recall, Short Delay Recall, Long Delay). These measures are aggregated to arrive at one reported value. The individual tests are first selected via factor analysis, then the selected raw scores are standardized to baseline controls by age and education group. The final domain score is calculated by averaging available individual z-standardized test scores.	Baseline and annually up to 5 years
Primary	Change in Cognition Domain	Using assessment: FACT-Cog and PCI Sub-scale. The measures are aggregated to arrive at one reported value. Change in cognition is calculated based on the official FACT-Cog scoring manual.; The total score is calculated by summing the available items among all 37 items when no more than 30 items are missing.; The PCI subscale score is calculated by summing the available items among all 18 items when no more than 8 items are missing.	Baseline and annually up to 5 years
Secondary	Change in Quality of Life	Using Functional Assessment of Cancer Therapy-Breast quality of life measure (FACT-B)	Baseline and annually up to 5 years
Secondary	Change in Quality of Life	Using Medical Outcome Study measure (MOS)	Baseline and annually up to 5 years
Secondary	Change in Quality of Life	Using Short Form Health Survey measure (SF-12)	Baseline and annually up to 5 years
Secondary	Change in cancer-related symptoms (including fatigue, sleep, pain, anxiety and depression)	Using survey data	Baseline and annually up to 5 years
Secondary	Biomarkers of aging (genotype, inflammatory biomarkers, telomere length, p16, miRNA)	Using annual biospecimen collection of blood or saliva	Baseline and annually up to 5 years
Secondary	Grip Strength Test	Participant's grip strength will be measured using the Jamar Plus Digital dynamometer. The participant should be in a standing position, arms at their side, not touching their body with elbow bent slightly. If subjects are unable to stand comfortably, they will be seated in a chair with their feet touching the ground with their elbow bent to 90 degrees and the arm against their trunk with a neutral wrist. Participants squeeze the Jamar Plus Digital dynamometer as hard as they can for a count of three. The dynamometer provides a digital reading of force in pounds. A practice trial at less than full force and one test trial are completed with each hand. The test takes approximately three minutes to administer. Dominant vs. Non-Dominant Hand (i.e., handedness) is assessed at the outset.	Baseline and annually up to 5 years
Secondary	Actigraphy/Change in Sleep	To obtain an objective assessment of both daytime and nighttime sleeping, participants will wear the actigraph on the dominant wrist (unless that arm is paralyzed) for one week. The Actigraph Motionlogger (Ambulatory Monitoring, Inc. Ardsley, NY), is a wrist-mounted actigraph that records activity and illumination exposure using an accelerometer, a light transducer and a microprocessor. Commercially available software uses validated algorithms that take into account wrist movement immediately before and after an epoch of interest; wrist activity below an established threshold is interpreted as sleep and wrist activity above that threshold is interpreted as wakefulness as validated in older adults. Agreement between wrist actigraphy and EEG (the gold standard method for sleep assessment) scoring of sleep variables (e.g., total sleep time) is 89-95% in older adults.	Baseline and annually up to 5 years