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Older Breast Cancer Patients: Risk for Cognitive Decline (TLC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03451383
Recruitment Status : Active, not recruiting
First Posted : March 1, 2018
Last Update Posted : April 24, 2020
Sponsor:
Collaborators:
Memorial Sloan Kettering Cancer Center
Indiana University
H. Lee Moffitt Cancer Center and Research Institute
City of Hope Medical Center
Hackensack Meridian Health
Information provided by (Responsible Party):
Jeanne Mandelblatt, Georgetown University

Tracking Information
First Submitted Date January 29, 2018
First Posted Date March 1, 2018
Last Update Posted Date April 24, 2020
Actual Study Start Date August 1, 2010
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: February 22, 2018)
  • Change in Attention [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: NAB Digits Forward and Backward
  • Change in Processing Speed [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: Trailmaking A and B
  • Change in Processing Speed [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: Digit Symbol Subtest - Wechsler Adult Intelligence Test-III
  • Change in Processing Speed [ Time Frame: Baseline and annually up to 5 years ]
    Using assessment: The Timed Instrumental Activities of Daily Living
  • Change in Executive Function [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: Trailmaking A and B
  • Change in Executive Function [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: Digit Symbol Subtest - Wechsler Adult Intelligence Test-III
  • Change in Executive Function [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: Controlled Oral Word Association Test
  • Change in Executive Function [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: NAB Driving Scenes
  • Change in Executive Function [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: NAB Figure Drawing
  • Change in Learning [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: Logical Memory I and II (Wechsler Memory Scale)
  • Change in Learning [ Time Frame: Baseline and annually up to 5 years ]
    Using neuropsychological test: NAB List Learning
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: February 22, 2018)
  • Change in Quality of Life [ Time Frame: Baseline and annually up to 5 years ]
    Using Functional Assessment of Cancer Therapy-Breast quality of life measure (FACT-B)
  • Change in Quality of Life [ Time Frame: Baseline and annually up to 5 years ]
    Using Medical Outcome Study measure (MOS)
  • Change in Quality of Life [ Time Frame: Baseline and annually up to 5 years ]
    Using Short Form Health Survey measure (SF-12)
  • Change in cancer-related symptoms (including fatigue, sleep, pain, anxiety and depression) [ Time Frame: Baseline and annually up to 5 years ]
    Using survey data
  • Biomarkers of aging (genotype, inflammatory biomarkers, telomere length, p16, miRNA) [ Time Frame: Baseline and annually up to 5 years ]
    Using annual biospecimen collection of blood or saliva
  • Change in physical activity [ Time Frame: Baseline and annually up to 5 years ]
    Using self-report
  • Change in physical activity [ Time Frame: Baseline and annually up to 5 years ]
    Using actigraphy
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Older Breast Cancer Patients: Risk for Cognitive Decline
Official Title Older Breast Cancer Patients: Risk for Cognitive Decline. The Thinking and Living With Cancer (TLC) Study
Brief Summary The goal of this study is to evaluate the impact of systemic therapy on cognition in older breast cancer patients, explore which domains are most affected, measure associations between cognitive decline and QOL, and describe how APOE and COMT polymorphisms, inflammatory biomarkers and physical activity 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.
Detailed 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, test associations between cognition and quality of life (QOL) and evaluate whether APOE and COMT polymorphisms, inflammatory biomarkers and physical activity 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 425 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, psychosocial factors, QOL and activities of daily living (IADLS). Investigators will abstract clinical data from medical records. Investigators will obtain blood or saliva to test for APOE and COMT 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 also have the option of participating in physical activity monitoring for one week. Subjects will also have the option to participate in neuroimaging. Investigators conduct follow-up interviews and repeat the neuropsychological testing 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, Working Memory, and Psychomotor Speed Domain. In secondary analyses, investigators examine changes in scores on 4 additional domains to assess broader cognitive function and examine questions of differential impact: Language; Executive Functioning; Learning and Memory; Visual-spatial.

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.

Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
A total of up to 27ml of blood will be collected at each time point by trained staff for APOE and COMT DNA testing, inflammatory biomarkers and for storage of DNA for future tests. 2-3 6mL lavender top vacutainer tubes containing ethylenediamine tetraaceticacid (EDTA) will be used for DNA extraction, biobanking and inflammatory biomarkers. 1 4ml CPT tube will be collected for biobanking. Up to 2 2.5ml PAXgene tubes will be collected for future DNA and RNA research. If a blood draw is not possible, up to 2ml of saliva will be collected.
Sampling Method Non-Probability Sample
Study Population Women age 60+ with a newly diagnosed breast adenocarcinoma staged 0-3 and matched controls.
Condition
  • Cancer, Breast
  • Age-related Cognitive Decline
  • Cognitive Decline
Intervention Not Provided
Study Groups/Cohorts
  • Breast Cancer Case
    Women age 60+ with a newly diagnosed breast adenocarcinoma staged 0-3.
  • Non-Cancer Controls
    Women age 60+ with no diagnosis of breast cancer.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Active, not recruiting
Estimated Enrollment
 (submitted: March 13, 2019)
1300
Original Estimated Enrollment
 (submitted: February 22, 2018)
850
Estimated Study Completion Date December 31, 2021
Estimated Primary Completion Date December 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

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

Sex/Gender
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Female breast cancer cases and female matched non-cancer controls
Ages 60 Years to 105 Years   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03451383
Other Study ID Numbers 2008-363
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Jeanne Mandelblatt, Georgetown University
Study Sponsor Georgetown University
Collaborators
  • Memorial Sloan Kettering Cancer Center
  • Indiana University
  • H. Lee Moffitt Cancer Center and Research Institute
  • City of Hope Medical Center
  • Hackensack Meridian Health
Investigators
Principal Investigator: Jeanne Mandelblatt Lombardi Comprehensive Cancer Center
PRS Account Georgetown University
Verification Date April 2020