Clinical trial NCT03515356: Exercise to Reduce Chemotherapy-Induced Peripheral Neuropathy
Official title: Exercise to Reduce Chemotherapy-Induced Peripheral Neuropathy: A Pilot RCT
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Gastrointestinal Cancer
Colorectal Cancer
Pancreatic Cancer
Gastric Cancer
Stomach Cancer
Esophageal Cancer
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
Collaborators: name: Unity Health Toronto
First posted: 2018-05-03
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: This randomized, controlled, pilot experiment will evaluate the effects of an aerobic walking intervention on OIPN (oxaliplatin-induced peripheral neuropathy) in patients with gastrointestinal (GI) cancer who are already prescribed oxaliplatin (85 mg/m2 every other week for at least six cycles) by their oncologists. Oxaliplatin is a standard chemotherapy treatment for invasive GI cancers that causes OIPN in 85-95% of patients.

Detailed description: Background: Over 190,000 men and women will be diagnosed in 2018 with invasive gastrointestinal (GI) cancers (e.g, colorectal and gastric cancer) for which oxaliplatin is a standard chemotherapy treatment. However, 85-95% of these patients develop oxaliplatin-induced peripheral neuropathy (OIPN). Currently, OIPN is the primary dose-limiting factor of oxaliplatin-based regimens, because persistent OIPN can impair physical function and quality of life (QOL) years after treatment completion. There are no effective treatments for OIPN. Four randomized controlled trials and two quasi-experiments have reported positive effects of at least 10 minutes/day of moderate-intensity aerobic exercise, 2-5 days/week over at least 6-8 weeks on chemotherapy-induced peripheral neuropathy. Exercise-enhanced circulation could re-distribute neurotoxic drugs away from vulnerable neurons, reduce oxidative stress, and help to prevent OIPN. However, all the prior trials had critical study limitations and all but two studies evaluated OIPN as a secondary outcome. Thus, this prospective, randomized, controlled, pilot experiment will evaluate the efficacy of an aerobic walking intervention for OIPN in GI cancer patients who are already prescribed oxaliplatin (85 mg/m2 every other week for at least six cycles) by their oncologists. The "MI-Walk intervention"- an 8-week motivational enhancement therapy (MET)- and home-based aerobic walking intervention-will be tested in this study.

Specific aims: The specific aims and hypotheses are to:

Aim 1: Evaluate the effect of the MI-Walk Intervention on OIPN severity at 8 weeks (T6) compared to physical activity (PA) education alone.

Hypothesis: Participants who receive the MI-Walk intervention will exhibit less severe OIPN at T6 than participants who receive PA education alone.

Aim 2: Explore the effect of the MI-Walk intervention on total oxaliplatin received, and QOL at T6 compared to PA education alone.

Hypothesis: Participants who receive the MI-Walk intervention will receive higher total doses of oxaliplatin and report higher QOL at T6 than participants who receive PA education alone.

Aim 3: Evaluate the feasibility of the MI-Walk intervention. Research Questions: Among patients receiving oxaliplatin, 1) how acceptable is the intervention? 2) what percent of patients will enroll in, complete, and adhere to the walking intervention? 3) what participant characteristics are associated with study compliance, adherence, completion, and acceptability? 4) What, if any, adverse events will result from the MI-Walk intervention?

Study design: Sixty GI cancer patients will be recruited at multiple cancer clinics within the week before their second oxaliplatin cycle. All participants will receive a PA education pamphlet. Half (n=30) will receive the MI-Walk Intervention. These patients will receive a tailored progressive walking plan, supplemental cancer treatment \& exercise education, patient testimony, HR-enabled pedometer and PA-tracking app, exercise diary, and semi-scripted brief MET (motivational interviewing, SMAART goals, and if-then statements) from research staff before practicing the intervention at home for 8 weeks. Additional brief MET sessions at 2 (T3) and 4 weeks (T4), progress summaries at T3, T4, and T6, a private email group, weekly group walking events, and peer accountability phone calls/email will be used to engage and support participants. To level attention, both groups will receive regular phone assessments of intervention-related adverse events at 1 week (T2), T3, T4, and 6 weeks (T5). Outcomes will be measured at (T1) and 8 weeks after (T6) intervention initiation. The outcome measures include the 0-10 NRS of OIPN symptom severity (primary outcome measure); and EORTC QLQ-CIPN20 self-report survey, cumulative oxaliplatin dose, and EORTC QLQ-C30. The study will also record feasibility, adherence, acceptability, and intervention fidelity data. Multiple linear regression will be used to evaluate the inter-group differences in the T1 to T6 change in mean NRS scores (OIPNΔ), controlling for T6 total oxaliplatin received (OXALIT6), and the interaction between the intervention and OXALIT6. Mediation analysis will be used to explore the secondary outcomes.

Future Directions: This study will be among the first to provide efficacy and feasibility data for an 8-week home-based aerobic walking intervention to reduce OIPN - a common chemotherapy side effect, for which there are no good treatments. This pilot study will inform the design of larger phase III trials to evaluate the efficacy of aerobic walking for OIPN, and potential mediators (e.g., vascular biomarkers) in this relationship.

Eligibility criteria: Inclusion Criteria:

* Diagnosed GI cancer (e.g, colorectal, gastric, pancreatic, esophageal, bowel);
* Scheduled to receive at least 6 cycles of oxaliplatin (85 mg/m2);
* Receiving care at the University of Michigan or St. Joseph Cancer Clinics;
* A Karnofsky Performance Status ≥ 80% or an Eastern Cooperative Oncology Group Status 0 to 1;
* Voluntarily consented to participate in all intervention components.

Exclusion Criteria:

* Exercise- or mobility-limiting cardiovascular, pulmonary, musculoskeletal, or psychological disease, based on the EMR (electronic medical record) past medical history and consultation with the medical oncologist;
* Scheduled major surgery during the study time period;
* Pre-existing peripheral neuropathy prior to chemotherapy (potentially due to diabetes, central nervous system malignancy, vitamin deficiency, heredity, nerve compression injury, non-surgically corrected carpal tunnel disease, or alcohol dependence) per patient self-report in response to brief screening questions noted in the pre-screening section;
* Pregnancy;
* Inability to read or speak English;
* Prognosis of less than three months.

Primary outcomes:
measure: Sensory neuropathy at 8 weeks
timeFrame: At 8 weeks
Secondary outcomes:
measure: Motor Neuropathy at 8 weeks
timeFrame: At 8 weeks
measure: Autonomic Neuropathy at 8 weeks
timeFrame: At 8 weeks
measure: Oxaliplatin dose at 8 weeks
timeFrame: At 8 weeks
measure: Quality of life at 8 weeks
timeFrame: At 8 weeks
measure: Mood at 8 weeks
timeFrame: At 8 weeks
Other outcomes:
measure: Exercise Adherence - Weekly Minutes of Moderate to Vigorous Physical Activity (MVPA)
timeFrame: Week 1 to week 8
measure: Total Daily Minutes of MVPA at 8 weeks
timeFrame: At 8 weeks
measure: Adapted Acceptability E-scale
timeFrame: 8 weeks
measure: Adverse event incidence
timeFrame: Week 1 to week 8
measure: Motivational Interviewing (MI) Fidelity Measure at Study Initiation
timeFrame: Day 1
measure: MI Fidelity Measure Mid-Study
timeFrame: 6 months
measure: MI Fidelity Measure at 9 months
timeFrame: 12 months
Locations:
city: Ann Arbor
country: United States
facility: The University of Michigan Comprehensive Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Brighton
country: United States
facility: St. Joseph Mercy Brighton Health Center
state: Michigan
city: Brighton
country: United States
facility: Brighton Center for Specialty Care
state: Michigan
city: Canton
country: United States
facility: St. Joseph Mercy Health System
state: Michigan
city: Chelsea
country: United States
facility: St. Joseph Mercy Chelsea Cancer Center
state: Michigan
city: Northville
country: United States
facility: The University of Michigan Northville Health Center
state: Michigan
Study officials:
affiliation: University of Michigan School of Nursing
name: Grace Kanzawa-Lee, BSN, RN
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Michigan School of Nursing
name: Ellen M Lavoie Smith, PhD
role: PRINCIPAL_INVESTIGATOR
References: