||1U01CA271279-01 Interpret this number
||Lsu Pennington Biomedical Research Ctr
||Adaptive Randomization of Aerobic Exercise During Chemotherapy in Colon Cancer
Patients with colon cancer who require chemotherapy dose reductions and treatment delays are twice as likely
to experience disease recurrence and death than patients who complete their full chemotherapy dose on time.
Up to 60% of patients develop toxicities of sufficient severity to require chemotherapy dose reductions or
treatment delays. We hypothesize that aerobic exercise improves chemotherapy relative dose intensity and
reduces patient-reported chemotherapy toxicities by improving the calibration of chemotherapy through
changes in body composition and altering immune function. In response to RFA-CA-21-031, we will conduct a
Bayesian, multi-stage, response-adaptive, dose-ranging trial of aerobic exercise. Participants will be 219 stage
II-III colon cancer survivors recruited from three diverse socioeconomic, racial, and geographic regions (Baton
Rouge, LA; Boston, MA; Oakland, CA). The first 80 participants are randomized to 1 of 5 groups equally:
moderate-intensity aerobic exercise at 75 min/wk, 150 min/wk, 225 min/wk, 300 min/wk, or attention control
(stretching). This is followed by adaptive randomization in which subsequent participants are assigned to an
exercise group in a ratio proportional to the probability that the specific exercise group improves chemotherapy
dose intensity and is feasible. Exercise is chemotherapy-periodized with more and less demanding weeks to
accommodate cyclical variations in patient-reported symptoms. Aim 1 will evaluate the dose-response effects
of moderate-intensity aerobic exercise compared with attention control on chemotherapy relative dose intensity
(primary endpoint). Aim 2 will determine the effect of moderate-intensity aerobic exercise compared with
control on gastrointestinal and peripheral neuropathy symptoms assessed using the Patient-Reported
Outcomes version of the Common Terminology Criteria for Adverse Events [PRO-CTCAE (key secondary
endpoint)]. Aim 3 will determine the effect of moderate-intensity aerobic exercise compared with control on
whole-body tissue distribution (total body fat mass and lean mass) measured using dual-energy x-ray
absorptiometry. Aim 4 will determine the effect of moderate-intensity aerobic exercise compared with control
on changes in neutrophil counts, phenotypes, and functions (biomarkers of neutrophil effector functions
including elastase, citrullinated Histone H3, and myeloperoxidase and direct measures of chemotaxis and
oxidative burst). This study will leverage a transdisciplinary team's synergies to identify an exercise
prescription that is patient-centered and proven to have a high probability of clinical benefit. This study will
directly inform clinical practice guidelines that recognize exercise as an essential supportive care intervention
for chemotherapy and establish exercise training as obligatory for delivering high-quality, evidence-based care
to colon cancer survivors.
The association of abdominal adiposity with premature discontinuation of postoperative chemotherapy in colon cancer.
, Meyerhardt J.A.
, Cespedes Feliciano E.M.
, Cheng E.
, Caan B.J.
Clinical nutrition (Edinburgh, Scotland), 2022 Jul; 41(7), p. 1600-1604.