Exercise and Low-Dose Ibuprofen for Cognitive Impairment in Colorectal Cancer Patients Receiving Chemotherapy

PRIMARY OBJECTIVE:

I. To provide preliminary data on the individual effects of exercise and ibuprofen, as well
as the combined effect of both interventions, on alleviating chemotherapy-related cognitive
impairment (CRCI) in colorectal cancer patients receiving chemotherapy compared to health
education and placebo controls, as assessed by the Functional Assessment of Cancer
Therapy-Cognitive Function (FACTCog).

SECONDARY OBJECTIVES:

I. To provide preliminary data on the individual effects of exercise and ibuprofen , as well
as the combined effect of both interventions, on alleviating CRCI in colorectal cancer
patients receiving chemotherapy compared to health education and placebo controls by
objective assessments of cognitive function.

II. To provide preliminary data on the individual effects of exercise and ibuprofen , as well
as the combined effect of both interventions, on alleviating CRCI in colorectal cancer
patients receiving chemotherapy compared to health education and placebo controls on
phone-based cognitive function measures (digit span, word recall, digits backward, CALVT,
category fluency; all from BTACT).

III. To provide preliminary data on the individual effects of exercise and ibuprofen, as well
as the combined effect of both interventions, on serum pro-inflammatory (MCP-1, IL- 6, IL-8,
TNF-alpha, sTNFR2, sTNFR1, IL-1beta) and anti-inflammatory (sIL-1Ra, IL-10)
cytokines/receptors in colorectal cancer patients receiving chemotherapy compared to health
education and placebo controls.

IV. To provide preliminary data on the mediating effects of cytokine concentrations on the
CRCI changes due to exercise and ibuprofen (as well as the combined effect of both
interventions), in colorectal cancer patients receiving chemotherapy compared to health
education and placebo controls on cytokines/receptors.

OUTLINE: Patients are randomized into 1 of 4 arms.

ARM I: Patients receive ibuprofen orally (PO) twice a day (BID) for 6 weeks and participate
in a discussion of "Chemotherapy and You" pamphlet.

ARM II: Patients receive placebo PO BID for 6 weeks and participate in a discussion of
"Chemotherapy and You" pamphlet.

ARM III: Patients receive placebo PO BID for 6 weeks. Patients also participate in home-based
walking and progressive resistance exercise over 20-60 minutes 3 to 5 times per week for 6
weeks.

ARM IV: Patients receive ibuprofen PO BID for 6 weeks. Patients also participate in
home-based walking and progressive resistance exercise over 20-60 minutes 3 to 5 times per
week for 6 weeks.

After completion of study, patients are followed up periodically.

Inclusion Criteria:

- Have a primary diagnosis of non-metastatic colorectal cancer and have had surgery and
are now receiving adjuvant chemotherapy

- Report cognitive difficulties of 3 or higher (on a scale of 0 = ?Not Present? to 10 =
?As Bad As You Can Imagine?) to the REDCap Screening Form question, ?Are you currently
experiencing any cognitive problems (such as in your memory, attention, concentration,
multi-tasking) since your cancer diagnosis?? at chemotherapy cycle 2 or after

- Be scheduled to receive at least 6 weeks of oral or intravenous (IV) chemotherapy
during the study intervention period; therapeutic clinical trial participants are
allowed

- Agree not to take a daily dosage of an non-steroidal anti-inflammatory drug (NSAID)
except 81 mg cardioprotective aspirin for the 6-week intervention period; (higher
doses of an NSAID on an ?as needed? basis for acute pain management are permitted but
should not exceed more than 1000 mg for one day per week)

- Have the approval of their treating physician to participate in exercise testing
(i.e., 6-minute walk test) and a low to moderate intensity home-based walking and
progressive resistance exercise program; (physician must sign eligibility checklist
prior to registration)

- Have the approval of their treating physician to receive the 6 week ibuprofen/placebo
regimen (200 mg twice a day and doses 8 hours apart); (physician must sign eligibility
checklist prior to registration)

- Be able to swallow medication

- Be able to read English

- Not be pregnant or become pregnant during the study if the participant is a woman of
child-bearing potential (i.e., women who are pre-menopausal or not surgically
sterile); documentation of pregnancy can be taken from the medical record

- 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 confirmed metastatic disease

- Be diagnosed with a neurodegenerative disease

- Have a history of peptic ulcer disease within the last 12 months unless adequately
treated as assessed by the participant?s primary care physician or medical oncologist

- Be receiving radiation treatment during study intervention period

- Be identified as in the maintenance (A) or action (B) stage of physical activity as
assessed by the single-item Exercise Stages of Change and exercising at least 150
min/wk of moderate intensity physical activity

- A. Maintenance stage: Participant exercises regularly and has been for MORE than
6 months

- B. Action stage: Participant exercises regularly and has been for LESS than 6
months

- C. Preparation stage: Participant does not exercise regularly but intends to in
the next 30 days

- D. Contemplation stage: Participant does not exercise regularly but intends to in
the next 6 months

- E. Pre-contemplation stage: Participant does not exercise regularly and does not
intend to in the next 6 months

- Have a contraindication to NSAIDs at the oncologist?s discretion (i.e., allergy,
worsening of ongoing medical problem due to NSAID, low platelet count from
chemotherapy, and uncontrolled condition such as hypertension or asthma)

- Have physical limitations (e.g., cardiorespiratory, orthopedic, central nervous
system) that contraindicate participation in exercise testing (i.e., 6-minute walk
test) or a low to moderate home-based walking and progressive resistance program, as
assessed by the oncologist

- Have had a myocardial infarction or other major heart complications within the past 6
months

- 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 with antiplatelet
activities

- Be colorblind

- Diagnosed alcoholism within the last 5 years