Cognitive Impairment, Malignant Neoplasm
Conditions
Brief summary
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.
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.
Interventions
OTHERQuestionnaire Administration
Ancillary studies
DRUGIbuprofen
Given PO
OTHERPlacebo
Given PO
Sponsors
National Cancer Institute (NCI)
University of Rochester NCORP Research Base
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | Up to 41 days post-intervention | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibuprofen 200mg BID 200mg ibuprofen (taken twice a day at least 8 hours apart) for a period of 6 weeks.
Ibuprofen: 200 mg BID and 8 hours apart | 45 |
| Placebo 200mg placebo (taken twice a day at least 8 hours apart) for a period of 6 weeks.
Placebo: 200mg BID and 8 hours apart | 42 |
| Total | 87 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
| Overall Study | Withdrawn due to medical problem | 3 | 2 |
Baseline characteristics
| Characteristic | Ibuprofen 200mg BID | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.3 Years STANDARD_DEVIATION 12.5 | 54.6 Years STANDARD_DEVIATION 12.8 | 55 Years STANDARD_DEVIATION 12.6 |
| Cancer Stage Stage 1 | 7 Participants | 2 Participants | 9 Participants |
| Cancer Stage Stage 2 | 8 Participants | 13 Participants | 21 Participants |
| Cancer Stage Stage 3 | 16 Participants | 12 Participants | 28 Participants |
| Cancer Stage Stage 4 | 10 Participants | 11 Participants | 21 Participants |
| Cancer Stage Unknown or Not Reported | 4 Participants | 4 Participants | 8 Participants |
| Cancer Type Breast | 20 Participants | 20 Participants | 40 Participants |
| Cancer Type Colorectal | 14 Participants | 11 Participants | 25 Participants |
| Cancer Type Other | 10 Participants | 11 Participants | 21 Participants |
| Cancer Type Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Chemotherapy Actively Receiving | 37 Participants | 34 Participants | 71 Participants |
| Chemotherapy Not Actively Receiving | 7 Participants | 8 Participants | 15 Participants |
| Chemotherapy Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Education Level 4 Year Degree | 16 Participants | 12 Participants | 28 Participants |
| Education Level Graduate Degree | 9 Participants | 12 Participants | 21 Participants |
| Education Level Highschool/GED | 9 Participants | 5 Participants | 14 Participants |
| Education Level Less than 4 Year Degree | 9 Participants | 11 Participants | 20 Participants |
| Education Level Some High School or Less | 1 Participants | 0 Participants | 1 Participants |
| Education Level Unknown or Not Reported | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 41 Participants | 38 Participants | 79 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 40 Participants | 37 Participants | 77 Participants |
| Sex: Female, Male Female | 37 Participants | 37 Participants | 74 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 42 |
| other Total, other adverse events | 15 / 45 | 15 / 42 |
| serious Total, serious adverse events | 2 / 45 | 3 / 42 |
Outcome results
Primary
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.
Time frame: Up to 41 days post-intervention
Population: Whenever the 6-week number of subjects or baseline number of subjects is less than the number reported per arm this is due to the data not being available. n=36 for Placebo (3-withdrawal by subject, 1- withdrawal due to medical issue) ; n=37 for Ibuprofen (3-withdrawal by subject, 3 - withdrawal due to medical issue, 1-lost to follow-up\*)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ibuprofen 200 mg BID | Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | Baseline (Pre) | 89.98 score on a scale | Standard Deviation 27.82 |
| Ibuprofen 200 mg BID | Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | 6 Weeks (Post) | 105.54 score on a scale | Standard Deviation 25.44 |
| Ibuprofen 200 mg BID | Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | Change from Baseline(Post - Pre) | 14.59 score on a scale | Standard Deviation 22.02 |
| Placebo | Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | Baseline (Pre) | 91.08 score on a scale | Standard Deviation 25.98 |
| Placebo | Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | 6 Weeks (Post) | 107.75 score on a scale | Standard Deviation 24.83 |
| Placebo | Effects of Ibuprofen on Alleviating Chemotherapy-related Cognitive Impairment | Change from Baseline(Post - Pre) | 15.52 score on a scale | Standard Deviation 21.43 |
p-value: 0.7917ANCOVA