Low-Dose Ibuprofen in Improving Cognitive Impairment in Patients With Cancer

Phase II Study of Low-Dose Ibuprofen for Cognitive Problems in Patients With Cancer

This randomized phase II trial studies how well low-dose ibuprofen in improving cognitive impairment in patients with cancer. Anti-inflammatory agents, such as ibuprofen, may slow the decline of cognitive processes and diseases involving the brain.

Study Overview

• Status: Completed
• Conditions: Cognitive Impairment; Malignant Neoplasm
• Intervention / Treatment: Other: Placebo; Other: Questionnaire Administration; Drug: Ibuprofen

Detailed Description

PRIMARY OBJECTIVES:

I. To provide preliminary data on the effect of ibuprofen on alleviating chemotherapy-related cognitive impairment (CRCI) in cancer patients receiving chemotherapy or who have received chemotherapy within the last 6 months compared to a placebo control, as assessed by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog).

OUTLINE: Patients are randomized into 1 of 2 arms.

ARM I: Patients receive ibuprofen orally (PO) twice daily (BID) for 6 weeks.

ARM II: Patients receive placebo PO BID for 6 weeks.

After completion of study, patients are followed up periodically.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Burbank, California, United States, 91505
      • Providence Saint Joseph Medical Center/Disney Family Cancer Center
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Regional Hematology and Oncology PA
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • Nanticoke Memorial Hospital
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • Idaho
    • Boise, Idaho, United States, 83712
      • Saint Luke's Mountain States Tumor Institute
    • Fruitland, Idaho, United States, 83619
      • Saint Luke's Mountain States Tumor Institute - Fruitland
    • Meridian, Idaho, United States, 83642
      • Saint Luke's Mountain States Tumor Institute - Meridian
    • Nampa, Idaho, United States, 83686
      • Saint Luke's Mountain States Tumor Institute - Nampa
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Carbondale, Illinois, United States, 62902
      • Memorial Hospital of Carbondale
    • Carterville, Illinois, United States, 62918
      • SIH Cancer Institute
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Centralia, Illinois, United States, 62801
      • Centralia Oncology Clinic
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Decatur, Illinois, United States, 62526
      • Cancer Care Specialists of Illinois - Decatur
    • Effingham, Illinois, United States, 62401
      • Crossroads Cancer Center
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Galesburg, Illinois, United States, 61401
      • Western Illinois Cancer Treatment Center
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare-Galesburg
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Valley Radiation Oncology
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University School of Medicine
    • Springfield, Illinois, United States, 62702
      • Springfield Clinic
    • Swansea, Illinois, United States, 62226
      • Southwest Illinois Health Services LLP
    • Swansea, Illinois, United States, 62226
      • Cancer Care Specialists of Illinois-Swansea
  • Michigan
    • Battle Creek, Michigan, United States, 49017
      • Bronson Battle Creek
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49048
      • Borgess Medical Center
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Niles, Michigan, United States, 49120
      • Lakeland Hospital Niles
    • Reed City, Michigan, United States, 49677
      • Spectrum Health Reed City Hospital
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Saint Joseph, Michigan, United States, 49085
      • Marie Yeager Cancer Center
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
    • Wyoming, Michigan, United States, 49519
      • Metro Health Hospital
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Maple Grove, Minnesota, United States, 55369
      • Fairview Maple Grove Medical Center
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • Monticello, Minnesota, United States, 55362
      • Monticello Cancer Center
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
    • Wyoming, Minnesota, United States, 55092
      • Fairview Lakes Medical Center
  • Missouri
    • Bonne Terre, Missouri, United States, 63628
      • Parkland Health Center-Bonne Terre
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Jefferson City, Missouri, United States, 65109
      • Capital Region Southwest Campus
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • Sainte Genevieve, Missouri, United States, 63670
      • Sainte Genevieve County Memorial Hospital
    • Sullivan, Missouri, United States, 63080
      • Missouri Baptist Sullivan Hospital
    • Sunset Hills, Missouri, United States, 63127
      • Missouri Baptist Outpatient Center-Sunset Hills
  • Nevada
    • Carson City, Nevada, United States, 89703
      • Carson Tahoe Regional Medical Center
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • OptumCare Cancer Care at Seven Hills
    • Henderson, Nevada, United States, 89052
      • Cancer and Blood Specialists-Henderson
    • Henderson, Nevada, United States, 89052
      • Las Vegas Cancer Center-Henderson
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    • Henderson, Nevada, United States, 89074
      • 21st Century Oncology-Henderson
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada-Horizon Ridge
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89119
      • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89128
      • OptumCare Cancer Care at MountainView
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89148
      • OptumCare Cancer Care at Fort Apache
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas, Nevada, United States, 89102
      • University Medical Center of Southern Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cancer and Blood Specialists-Shadow
    • Las Vegas, Nevada, United States, 89109
      • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    • Las Vegas, Nevada, United States, 89113
      • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    • Las Vegas, Nevada, United States, 89121
      • Cancer Therapy and Integrative Medicine
    • Las Vegas, Nevada, United States, 89128
      • Cancer and Blood Specialists-Tenaya
    • Las Vegas, Nevada, United States, 89128
      • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    • Las Vegas, Nevada, United States, 89148-2405
      • Las Vegas Cancer Center-Medical Center
    • Las Vegas, Nevada, United States, 89149
      • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    • Las Vegas, Nevada, United States, 89109
      • 21st Century Oncology
    • Las Vegas, Nevada, United States, 89128
      • 21st Century Oncology-Vegas Tenaya
    • Las Vegas, Nevada, United States, 89148
      • 21st Century Oncology-Fort Apache
    • Las Vegas, Nevada, United States, 89128
      • Ann M Wierman MD LTD
    • Las Vegas, Nevada, United States, 89102
      • Desert West Surgery
    • Las Vegas, Nevada, United States, 89103
      • Hope Cancer Care of Nevada
    • Las Vegas, Nevada, United States, 89169
      • University Cancer Center
    • Las Vegas, Nevada, United States, 89106
      • OptumCare Cancer Care at Oakey
    • Pahrump, Nevada, United States, 89048
      • Hope Cancer Care of Nevada-Pahrump
    • Reno, Nevada, United States, 89502
      • Renown Regional Medical Center
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
    • Reno, Nevada, United States, 89509
      • Radiation Oncology Associates
  • North Carolina
    • Asheville, North Carolina, United States, 28816
      • Hope Women's Cancer Centers-Asheville
    • Asheville, North Carolina, United States, 28801
      • Cancer Care of Western North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mission Hospital Inc-Memorial Campus
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Marietta Memorial Hospital
  • Oregon
    • Bend, Oregon, United States, 97701
      • Saint Charles Health System
    • Clackamas, Oregon, United States, 97015
      • Clackamas Radiation Oncology Center
    • Clackamas, Oregon, United States, 97015
      • Providence Oncology and Hematology Care Southeast
    • Coos Bay, Oregon, United States, 97420
      • Bay Area Hospital
    • Newberg, Oregon, United States, 97132
      • Providence Newberg Medical Center
    • Oregon City, Oregon, United States, 97045
      • Providence Willamette Falls Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97225
      • Providence Saint Vincent Medical Center
  • Pennsylvania
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
  • South Carolina
    • Clinton, South Carolina, United States, 29325
      • Greenville Health System Cancer Institute-Laurens
    • Easley, South Carolina, United States, 29640
      • Greenville Health System Cancer Institute-Easley
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29605
      • Greenville Memorial Hospital
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Butternut
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • Washington
    • Aberdeen, Washington, United States, 98520
      • Providence Regional Cancer System-Aberdeen
    • Anacortes, Washington, United States, 98221
      • Cancer Care Center at Island Hospital
    • Bellingham, Washington, United States, 98225
      • PeaceHealth Saint Joseph Medical Center
    • Centralia, Washington, United States, 98531
      • Providence Regional Cancer System-Centralia
    • Edmonds, Washington, United States, 98026
      • Swedish Medical Center-Edmonds
    • Everett, Washington, United States, 98201
      • Providence Regional Cancer Partnership
    • Issaquah, Washington, United States, 98029
      • Swedish Cancer Institute-Issaquah
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Lacey, Washington, United States, 98503
      • Providence Regional Cancer System-Lacey
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Seattle, Washington, United States, 98107
      • Swedish Medical Center-Ballard Campus
    • Seattle, Washington, United States, 98112
      • Kaiser Permanente Washington
    • Seattle, Washington, United States, 98104
      • Pacific Gynecology Specialists
    • Seattle, Washington, United States, 98122-4307
      • Swedish Medical Center-First Hill
    • Seattle, Washington, United States, 98122-5711
      • Swedish Medical Center-Cherry Hill
    • Shelton, Washington, United States, 98584
      • Providence Regional Cancer System-Shelton
    • Spokane, Washington, United States, 99204
      • Rockwood Cancer Treatment Center-DHEC-Downtown
    • Spokane, Washington, United States, 99218
      • Rockwood North Cancer Treatment Center
    • Spokane Valley, Washington, United States, 99216
      • Rockwood Clinic Cancer Treatment Center-Valley
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
    • Walla Walla, Washington, United States, 99362
      • Providence Saint Mary Regional Cancer Center
    • Yelm, Washington, United States, 98597
      • Providence Regional Cancer System-Yelm
  • Wisconsin
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a diagnosis of cancer and have had surgery and are now receiving adjuvant or neoadjuvant chemotherapy or who have received chemotherapy within the last 6 months; chemotherapy with concurrent radiation therapy (RT) is allowed

• Answer YES to the question: "Have you noticed any problems in your memory, attention, concentration, multi-tasking or other cognitive functions?" any time after initiation of chemotherapy cycle 1

  • NOTE: If a participant answers NO, they may be re-approached at a subsequent cycle
• Be able to swallow medication
• Be able to read English
• Have the ability to understand and to give written informed consent as assessed by the participant's primary care physician or medical oncologist

Exclusion Criteria:

• Have a confirmed brain tumor or brain metastases
• Be taking a regular daily dose of an NSAID NOTE: Daily doses of 81 mg aspirin are permitted and higher doses of an NSAID on an 'as needed' basis are permitted
• Be diagnosed with dementia or severe neurodegenerative disease
• Have a contraindication to NSAIDs at the oncologist's discretion (i.e., allergy, worsening of ongoing medical problem due to NSAID, very low platelet count from chemotherapy, full-dose anti-coagulation/high risk of bleeding, and uncontrolled conditions such as hypertension, asthma, or peptic ulcer disease)
• Have been hospitalized for treatment of a major psychiatric illness within the last five years
• Have a serum creatinine above 1.5 upper limit of normal (ULN) (collected within the past 4 weeks); ULN is per institutional definition
• Concurrent administration of warfarin, full dose aspirin, clopidogrel, apixaban or other medications known to increase the risk of bleeding or to interfere with antiplatelet activities
• Be colorblind
• Have active substance abuse (e.g. alcohol, drugs) per self-report or medical record

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (ibuprofen); Patients receive ibuprofen PO BID for 6 weeks.	Other: Questionnaire Administration; Ancillary studies; Drug: Ibuprofen; Given PO; Other Names: Advil; Motrin; (.+ -.)-p-Isobutylhydratropic acid; p-Isobutylhydratropic acid
Placebo Comparator: Arm II (placebo); Patients receive placebo PO BID for 6 weeks.	Other: Placebo; Given PO; Other Names: placebo therapy; PLCB; sham therapy; Other: Questionnaire Administration; Ancillary studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment	Will be assessed by the Functional Assessment of Cancer Therapy-Cognitive Function. Means, standard deviations, and 95% confidence intervals will be determined in order to estimate preliminary population variances and effect sizes. These statistical measures will be calculated by group for the Pre(Baseline) and Post(6 Weeks) measures of the Functional Assessment of Cancer Therapy-Cognitive Function scores as well as the change (post-pre) in the scores using the subjects that completed the study (complete case estimation). The complete case estimates will be compared to multiple imputation estimates based on all subjects that completed pre-intervention. An analysis of covariance will be run using Functional Assessment of Cancer Therapy-Cognitive Function post-intervention as the response. Higher scores indicate better function; range is 0 to 148.	Up to 41 days post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective assessments of cognitive functions	Will be measured by validated neuropsychological assessment of verbal memory, attention, and executive function and paper-based measures respectively.	Up to 41 days post intervention
Phone-based cognitive function	Analysis of covariance will be used as with the primary aim analyses to assess mean differences between cognitive function assessed by the remaining objective total scores at post-intervention.	Up to 41 days post intervention
Pro and anti-inflammatory cytokines/receptors analysis	Will assess the effects of the interventions on cytokines, hypothesizing that each intervention will reduce pro-inflammatory cytokines and increase anti-inflammatory cytokines using the same analysis or covariance analysis.	Up to 41 days post intervention
Cytokine concentrations	Will provide preliminary data on the mediating effects of cytokine concentrations on the chemotherapy-related cognitive impairment changes due to ibuprofen in cancer patients receiving chemotherapy or who have received chemotherapy within the last 6 months compared to placebo controls on cytokines/receptors. Will use path modeling to estimate indirect (mediation) effects, and bootstrapping to estimate the 95% confidence intervals. Will evaluate whether cytokines mediate the effect of the intervention on cognitive scores. Will involve a separate analysis for each cytokine, using linear models with arm, pre-intervention cognitive score and with/without cytokine post-pre change scores as model predictors. Will attempt to do a structural equation model where the mediator is a latent variable measured by changes in all the cytokines, and the response is a latent variable.	Up to 41 days post intervention

Collaborators and Investigators

• Sponsor: University of Rochester NCORP Research Base
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michelle C Janelsins, University of Rochester NCORP Research Base

Study record dates

Study Major Dates

• Study Start (Actual): May 26, 2017
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: June 7, 2017
• First Submitted That Met QC Criteria: June 12, 2017
• First Posted (Actual): June 14, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2023
• Last Update Submitted That Met QC Criteria: September 13, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Neoplasms; Cognitive Dysfunction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ibuprofen
• Other Study ID Numbers: URCC16092 (Other Identifier: University of Rochester NCORP Research Base); UG1CA189961 (U.S. NIH Grant/Contract); NCI-2017-00790 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); URCC-16092 (Other Identifier: CTEP); R21CA187500 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No