EXercise Influence on Taxane Side Effects (EXIT) Study

Sponsor

University of British Columbia (Other)

Overall Status

Completed

CT.gov ID

NCT02473861

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is a randomized control cross over trial of exercise training during or after taxane-containing chemotherapy treatment for breast cancer. Forty-three women with stage I-III breast cancer will be randomized to immediate or delayed thrice weekly exercise training for 8-12 weeks. The immediate exercise group will exercise during taxane chemotherapy and the delayed group will start exercise 2 weeks after completion of treatment. This design will allow for an assessment of the effects of exercise vs usual care during treatment, plus a comparison of the training response during vs. after chemotherapy.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms	Other: Exercise	N/A

Detailed Description

Purpose The purpose of this study is to evaluate the effects of aerobic and resistance exercise training relative to usual care during taxane-containing chemotherapy treatment for breast cancer.

Hypotheses

Relative to usual care, aerobic and resistance exercise training during taxane-containing chemotherapy treatment for breast cancer will:

mitigate the experience of patient reported outcomes
reduce medical management of taxane side effects and adverse events
attenuate autonomic dysfunction and maintain resting cardiovascular function and cardiovascular response to exercise

Objectives The primary aim of this study is to determine whether aerobic and resistance exercise training during taxane-containing chemotherapy treatment reduces patient-reported side effects, medical management and clinical adverse events reported relative to usual care. The secondary aim is to determine the whether aerobic and resistance exercise training during taxane-containing chemotherapy attenuates the occurrence of indices of autonomic dysfunction relative to usual care.
Research methods This study is a randomized control trial with crossover. The intervention consists of aerobic, resistance and balance training three times a week. Forty-three women with a stage I-III breast cancer diagnosis who are scheduled to receive taxane-containing chemotherapy will be randomized to immediate or delayed exercise (stratified by treatment protocol). Potential participants will be referred by oncologist referral, or will be self-referred by recruitment posters, social media or word of mouth.
Statistical analysis The primary outcome measure is the EORTC CIPN subscale of patient-reported symptoms related to neurotoxic chemotherapy. Secondary outcome measures include measures of autonomic dysfunction including heart rate and blood pressure variability, and medical management of taxane-related side effects, and clinical adverse events related to treatment.

The chemotherapy-induced peripheral neuropathy (CIPN) sub-scale of the EORTC Quality of life Questionnaire is used as the primary outcome measure to determine sample size. G*Power 3.0.10 was used to estimate sample size for independent t-tests between the two groups (at the 2-week post chemotherapy time point). At thirty-six participants, we will have 80% power to detect a medium (d=0.6) effect size in the EORTC CIPN-20 subscale at an alpha of 0.05 (one-tailed) . An additional 20% will be recruited to allow for dropout or non-adherence, making the final total sample size goal 43 participants.

Baseline characteristics and outcome measures of the two groups will be compared with independent t-tests. To assess the effect of the exercise intervention during treatment, independent t-tests will be used to compare the outcome measures at two weeks post completion of taxane chemotherapy if no difference exists between groups baseline measures. For the exercise group, all outcome measures at time point 2 will be compared to time point 3 using paired t-tests to assess maintenance over time. Independent t-tests will first be used to determine whether significant differences exists between groups for the three exploratory measure time points. If no differences exist, all data will be combined, and analyzed with a repeated measures analysis of variance to determine whether differences exist.

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

EXercise Influence on Taxane Side Effects (EXIT) Study

Actual Study Start Date :

Aug 1, 2015

Actual Primary Completion Date :

Jan 1, 2018

Actual Study Completion Date :

Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Immediate exercise arm The length of the intervention for the immediate exercise group will be determined by treatment protocol and could range from 8 to 13 weeks. The intervention can begin up to one week before the first treatment and will continue until 2 weeks after the final taxane-containing treatment. The intervention will consist of thrice weekly supervised aerobic and resistance exercise training.	Other: Exercise Moderate intensity aerobic and resistance training. Five minutes each of warm-up, cool-down, balance and flexibility will also be performed.
Experimental: delayed exercise arm The delayed exercise group will begin an exercise intervention two weeks after completion of their last taxane-containing chemotherapy treatment that will last the length of their taxane chemotherapy plus two weeks. If participants in the delayed exercise group have a surgery planned during the intervention time that will require >1 week off from exercise, the exercise intervention will be delayed until after the surgery. The intervention will consist of thrice weekly supervised aerobic and resistance exercise training.	Other: Exercise Moderate intensity aerobic and resistance training. Five minutes each of warm-up, cool-down, balance and flexibility will also be performed.

Arm

Intervention/Treatment

Experimental: Immediate exercise arm

The length of the intervention for the immediate exercise group will be determined by treatment protocol and could range from 8 to 13 weeks. The intervention can begin up to one week before the first treatment and will continue until 2 weeks after the final taxane-containing treatment. The intervention will consist of thrice weekly supervised aerobic and resistance exercise training.

Other: Exercise

Moderate intensity aerobic and resistance training. Five minutes each of warm-up, cool-down, balance and flexibility will also be performed.

Experimental: delayed exercise arm

The delayed exercise group will begin an exercise intervention two weeks after completion of their last taxane-containing chemotherapy treatment that will last the length of their taxane chemotherapy plus two weeks. If participants in the delayed exercise group have a surgery planned during the intervention time that will require >1 week off from exercise, the exercise intervention will be delayed until after the surgery. The intervention will consist of thrice weekly supervised aerobic and resistance exercise training.

Other: Exercise

Moderate intensity aerobic and resistance training. Five minutes each of warm-up, cool-down, balance and flexibility will also be performed.

Outcome Measures

Primary Outcome Measures

Change with treatment and maintenance post treatment in patient-reported taxane-related symptoms via the EORTC CIPN subscale [14-0 days pre taxane chemotherapy, 1-2 weeks after completion of half of planned taxane chemotherapy treatments, 2 weeks post completion of taxane chemotherapy, 10-15 weeks post completion of taxane chemotherapy]
European Organization for Research and Treatment of Cancer CIPN subscale

Secondary Outcome Measures

Change with treatment and maintenance post treatment of heart rate variability [14-0 days pre taxane chemotherapy, 2 weeks post completion of taxane chemotherapy, 10-15 weeks post completion taxane chemotherapy]
Electrocardiography will be used to assess heart rate variability during 10 minutes of supine rest
Change with treatment and maintenance post treatment of blood pressure variability [14-0 days pre taxane chemotherapy, 1-2 weeks after completion of half of planned taxane chemotherapy treatments, 2 weeks post completion of taxane chemotherapy, 10-15 weeks post completion of taxane chemotherapy]
A Finometer will be used to assess blood pressure variability from supine to standing posture
Number of participants requiring medical management of taxane side effects [Will be extracted from medical records 0-6 months after completion of chemotherapy]
Prescription of medications, dose delays, dose reductions will be abstracted from cancer treatment records
Number of participants with clinical reporting of adverse events during taxane-chemotherapy treatment [Will be extracted from medical records 0-6 months after completion of chemotherapy]
Oncological treatment notes will be reviewed for clinical notation of adverese events during taxane treatment

Other Outcome Measures

Change with treatment and maintenance post treatment of aerobic fitness via estimated peak oxygen consumption [14-0 days pre taxane chemotherapy, 2 weeks post taxane chemotherapy, 10-15 weeks post taxane chemotherapy]
Peak oxygen consumption be estimated from incremental cycle ergometer test
Change with treatment and maintenance post treatment of lower body muscular strength via estimated 1-repetition maximum leg press [14-0 days pre taxane chemotherapy, 2 weeks post taxane chemotherapy, 10-15 weeks post taxane chemotherapy]
Lower body strength be assessed by estimated 1 repetition maximum leg press
Change with treatment and maintenance post treatment of upper body muscular strength via handgrip strength [14-0 days pre taxane chemotherapy, 2 weeks post taxane chemotherapy, 10-15 weeks post taxane chemotherapy]
Handgrip strength will be assessed via handgrip dynamomemeter
Change during treatment and post treatment in cancer-related fatigue via revised Piper Fatigue Scale [14-0 days pre taxane chemotherapy, 0-3 days pre chemo cycle 3, 3-5 days post chemo cycle 3, 0-3 days pre chemo cycle 4, 2 weeks post taxane chemotherapy, 10-15 weeks post taxane chemotherapy]
Revised Piper Fatigue Scale will be administered electronically to assess change with the intervention but also across one cycle (third) of chemotherapy to investigate patterns in fatigue
Change in pain with treatment and improvement post treatment via Brief Pain Inventory [14-0 days pre taxane chemotherapy, 2 weeks post taxane chemotherapy, 10-15 weeks post taxane chemotherapy]
The Brief Pain Inventory will be administered electronically

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Born female
Age 19 or older
Histologically confirmed stage I-IIIA breast cancer diagnosis
Scheduled to receive neoadjuvant or adjuvant taxane-containing chemotherapy
Willing and able to attend baseline assessment prior to first taxane-containing treatment
Have reliable transportation to attend our exercise gym located near the Vancouver BCCA three times weekly for 8-13 weeks
Be able to read and communicate in English
Treating medical oncologist approval to participate

Exclusion Criteria:

Receipt of further chemotherapy treatments after taxane-containing treatments
Stage IV cancer
Acute or uncontrolled health conditions including heart disease, respiratory disease (COPD or severe asthma)
Diagnosis of diabetes at any time
Personal history of neurological disorder
Mobility issues that require a mobility aid or that prevent exercise on a bike, treadmill, or elliptical (includes orthopedic injury or arthritis that result in inability to exercise)
Body mass index ≥40 kg/m2
Previously received chemotherapy or thoracic radiation treatment