Exercise to Reduce Chemotherapy-Induced Peripheral Neuropathy

Colorectal Cancer Clinical Trial

Official title:

Exercise to Reduce Chemotherapy-Induced Peripheral Neuropathy: A Pilot RCT

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03515356
• Other study ID #: UMCC 2018.023
• Secondary ID: HUM00136639
• Status: Completed
• Phase: N/A
• Start date: June 13, 2018
• Est. completion date: June 24, 2019

Study information

• Verified date: March 2020
• Source: University of Michigan Rogel Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: June 24, 2019
• Est. primary completion date: June 24, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Esophageal Cancer
• Gastric Cancer
• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• Pancreatic Cancer
• Peripheral Nervous System Diseases
• Stomach Cancer
• Stomach Neoplasms

Intervention

Behavioral:
• MI-Walk Intervention
Eight-week motivational enhancement therapy and home-based aerobic walking intervention
• Physical Activity Education Pamphlet
Physical activity education pamphlet only

Locations

Country	Name	City	State
United States	St. Joseph Mercy Hospital	Ann Arbor	Michigan
United States	The University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Brighton Center for Specialty Care	Brighton	Michigan
United States	St. Joseph Mercy Brighton Health Center	Brighton	Michigan
United States	St. Joseph Mercy Health System	Canton	Michigan
United States	St. Joseph Mercy Chelsea Cancer Center	Chelsea	Michigan
United States	The University of Michigan Northville Health Center	Northville	Michigan

Sponsors (2)

Lead Sponsor	Collaborator
University of Michigan Rogel Cancer Center	St. Joseph Hospital Health Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exercise Adherence - Weekly Minutes of Moderate to Vigorous Physical Activity (MVPA)	A heart rate-enabled pedometer will be used to objectively measure adherence in the experimental group. The mean "active minutes" (minutes of moderate-vigorous physical activity) over eight weeks will be collected from a web-based application synchronized with the pedometer.	Week 1 to week 8
Other	Total Daily Minutes of MVPA at 8 weeks	The ActiGraph GT3X--a blinded wrist or hip-worn triaxial accelerometer--will be used to objectively measure activity counts per minute. The counts per minute will be transformed to total daily minutes of MVPA.	At 8 weeks
Other	Adapted Acceptability E-scale	The Acceptability E-Scale was adapted to assess acceptability of the walking intervention. Specifically, the survey asks participants to rate the difficulty, enjoyability, helpfulness in managing OIPN symptoms, and acceptability of the time requirement of the MI-Walk intervention. Each item is rated on a scale from one to five and the 15-item survey score ranges from 19 to 75.	8 weeks
Other	Adverse event incidence	Intervention-related adverse event incidence will be monitored throughout the study, using brief semi-scripted telephone interviews.	Week 1 to week 8
Other	Motivational Interviewing (MI) Fidelity Measure at Study Initiation	An external MI expert will formally review the fidelity of an MI session, using established MI evaluation criteria (the Motivational Interviewing Treatment Integrity Code [MITI]).	Day 1
Other	MI Fidelity Measure Mid-Study	An external MI expert will formally review the fidelity of an MI session, using the MITI.	6 months
Other	MI Fidelity Measure at 9 months	An external MI expert will formally review the fidelity of an MI session, using the MITI.	12 months
Primary	Sensory neuropathy at 8 weeks	The 9-item European Organisation of Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Chemotherapy-Induced Peripheral Neuropathy Scale (CIPN20) sensory subscale will be used to measure sensory neuropathy. Each item is rated on a scale from 1 ("not at all") to 4 ("very much"), and the total raw score ranges from 9 to 36. The raw scores will be linearly transformed to a 0 to 100 scale (higher scores represent worse CIPN severity).	At 8 weeks
Secondary	Motor Neuropathy at 8 weeks	The 8-item EORTC QLQ-CIPN20 motor subscale will be used to measure motor neuropathy. Each item is rated on a scale from 1 ("not at all") to 4 ("very much"), and the total raw score ranges from 8 to 32. The raw scores will be linearly transformed to a 0 to 100 scale (higher scores represent worse CIPN severity).	At 8 weeks
Secondary	Autonomic Neuropathy at 8 weeks	The 3-item EORTC QLQ-CIPN20 autonomic subscale will be used to measure autonomic neuropathy. Each item is rated on a scale from 1 ("not at all") to 4 ("very much"), and the total raw score ranges from 3 to 12. The raw scores will be linearly transformed to a 0 to 100 scale (higher scores represent worse CIPN severity).	At 8 weeks
Secondary	Oxaliplatin dose at 8 weeks	Cumulative oxaliplatin dose (mg/m2 of oxaliplatin received) data will be gathered from the electronic medical record (EMR).	At 8 weeks
Secondary	Quality of life at 8 weeks	The EORTC QLQ 30-Item Questionnaire (EORTC QLQ-C30) is a patient-reported measure of cancer-specific QOL. Participants rate the degree that each item has applied to them during the past week on a four-point Likert scale (1, not at all; 4, very much). The average of the item scores gives a raw score and the raw score will be transformed to a 0 to 100 scale. Higher scores indicate higher QOL.	At 8 weeks
Secondary	Mood at 8 weeks	The 4-item emotional functioning (EF) subscale of the EORTC QLQ-C30 will be used to measure mood. Participants rate the degree that each item has applied to them during the past week on a four-point Likert scale (1, not at all; 4, very much). The average of the item scores gives a raw score and the raw score will be transformed to a 0 to 100 scale. Higher scores indicate improved mood.	At 8 weeks