Clinical trial NCT03885817: Physically Active During Cancer Treatment (FAKT)
Official title: Physically Active During Cancer Treatment
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Neoplasms, Colorectal
Keywords: Exercise therapy
Fatigue
Adjuvant chemotherapy
Peripheral neuropathy, chemotherapy induced
Nutritional guide
Lead sponsor: St. Olavs Hospital
Sponsor class: OTHER
Collaborators: name: Alesund Hospital
name: Helse Nord-Trøndelag HF
name: Ullevaal University Hospital
name: Sorlandet Hospital HF
name: Asker & Baerum Hospital
name: Haukeland University Hospital
First posted: 2019-03-22
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This randomized controlled trial aims to investigate whether an individually tailored exercise program and nutritional guide can affect the development of self-reported peripheral sensory neuropathy and fatigue in patients with colorectal cancer receiving adjuvant chemotherapy.

Detailed description: Colorectal cancer is the second most common cancer in Norway with 4332 new cases in 2017. Standard of care is radical surgery followed by adjuvant chemotherapy for some, depending on the stage of the disease. Most commonly, a combination of Oxaliplatin and Capecitabine or 5-fluorouracil is given for 3 to 6 months.

A common side effect of Oxaliplatin is peripheral sensory neuropathy, which occur in different degree in over 90 % of the patients. There is no established treatment to prevent or reduce Oxaliplatin induced peripheral neuropathy. A few minor studies have been published indicating that physical activity can reduce the patient's experience of chemotherapy-induced peripheral neuropathy.

Most patients receiving chemotherapy will experience fatigue in some degree. It has been shown in several studies that exercise can reduce cancer related fatigue, though most studies have been performed among women with breast cancer.

There are a limited number of randomized controlled clinical trials looking at the effects of physical exercise during ongoing adjuvant chemotherapy in colorectal cancer patients. Thus, there is a clear need for further studies on physical exercise in this patient group.

In the period from January 2017 to November 2018 the investigators did a non-randomized pilot study to test the feasibility of the exercise intervention in this patient group, and to calculate sample size for the randomized trial.

The 9-item European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Chemotherapy Induced Peripheral Neuropathy (CIPN20) sensory subscale will be used to measure peripheral 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). A difference of 10 is considered clinically significant. The sample size calculation is based on a two-sided t-test. Aim is to demonstrate a difference in patient-reported sensory peripheral neuropathy between the two groups 3 months after randomization. It is postulated that the intervention group develops less degree of peripheral sensory neuropathy than the control group. Based on the answers obtained from the questionnaire in the pilot study, a standard deviation (SD) of 12.5 is assumed for the change between baseline and 3 months. To detect a difference of 10 with a strength of 80% and with a significance level of 0.05, there should be 25 patients in each arm. A drop out of 20% is taken into account based on experience in the pilot study. This suggests that 64 patients should be included in this study.

Patients scheduled for adjuvant Oxaliplatin based combination chemotherapy will be recruited from cancer clinics in Norway, and randomized to an intervention group or a control group. Before randomization and start of the first cycle of chemotherapy, the study participants will perform baseline testing and fill in the different questionnaires.

The intervention with exercise training starts around the same time as adjuvant chemotherapy starts, usually 4 -6 weeks postoperatively, and lasts as long as the adjuvant treatment, i.e. 3 - 6 months. Participants start with an individual session with a physiotherapist at the hospital. A treadmill submaximal heart rate test is done to give the participants instructions regarding the recommended intensity zones during cardio training.

The exercise intervention consists of three components: sensorimotor training (SMT), strength exercises, and aerobic training. The SMT and strength exercises are carried out twice a week as guided training together with the physiotherapist, each session lasting 30 minutes. In addition, instruction is given to do minimum 90 minutes a week of moderate intensity (60 - 75 % of maximum heart rate) home-based aerobic training, or 45 minutes with high intensity (80 - 85 % of maximum heart rate) aerobic training.

Participants in the intervention group receive a pulse watch to guide the intensity of the aerobic exercise. The participants will register completed training in a training log. Based on previous experience with physical activity and exercise, individual guidance is provided.

Once a month participants will fill out the form, Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF), and will be referred to a nutritionist if the score is 2 or higher. Regardless of the score on this form and group affiliation, participants may be referred to a nutritionist based on clinical judgment.

In the pilot study, also a qualitative study was carried out with semi-structured interviews evaluating patient's expectations and experiences regarding the physical exercise training. Depending on the information power obtained in the current sample, additional interviews of patients in this randomized trial might be done.

Eligibility criteria: Inclusion Criteria:

* Radical resection for colon- or rectal cancer past 3 months, and scheduled for adjuvant, Oxaliplatin-based, combination chemotherapy.
* Histologically confirmed adenocarcinoma.
* Able to read and understand Norwegian.
* Able to carry out the intervention.
* Performance Status (PS) 0 - 2.

Exclusion Criteria:

* Serious comorbidities that contraindicate physical exercise, based on the treating physician's assessment.
* Unable to give informed consent.
* Treated for other cancer last 5 years prior to inclusion (with the exceptions of basal cell carcinoma of the skin and carcinoma in situ in the cervix).
* Prior treatment with Oxaliplatin

Primary outcomes:
measure: Patient reported peripheral sensory neuropathy
timeFrame: Baseline to 3 months
Secondary outcomes:
measure: Fatigue
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Change in patient reported peripheral sensory neuropathy.
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Change in patient reported motor neuropathy
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Change in patient reported autonomic neuropathy
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Clinicians reported neuropathy
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in body mass index (BMI)
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in systolic blood pressure (sBP)
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in diastolic blood pressure (dBP)
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in waist circumference.
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in HDL-cholesterol
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in Triglycerides
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in Glycated hemoglobin (HbA1c)
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in Glucose
timeFrame: Baseline to 3, 6 and 12 months.
measure: Change in Body Composition
timeFrame: Baseline to 3 and 12 months
measure: Nutritional status
timeFrame: Baseline, 1, 2, 3, 4, 5 and 6 months
measure: Change in Quality Of Life: EORTC QLQ-C30 Version 3.0
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Completion of adjuvant treatment 1
timeFrame: 3 to 6 months
measure: Completion of adjuvant treatment 2
timeFrame: 3 to 6 months
measure: Completion of adjuvant treatment 3
timeFrame: 3 to 6 months
measure: Physical capacity
timeFrame: Baseline to 3, 6 and 12 months.
measure: Self-reported physical activity
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Muscle strength
timeFrame: Baseline to 3, 6 and 12 months.
measure: Balance 1
timeFrame: Baseline to 3, 6 and 12 months.
measure: Balance 2
timeFrame: Baseline to 3, 6 and 12 months.
measure: Haematological toxicity
timeFrame: Baseline to 6 months.
measure: Time before return to work
timeFrame: Baseline to 3, 6, 9, 12, 24 and 36 months
measure: Overall- and disease free survival
timeFrame: Baseline to 5 years
Other outcomes:
measure: Serious adverse events (SAE)
timeFrame: Baseline to 6 months
measure: Patient's expectations and experiences
timeFrame: Baseline, 3 and 6 months
measure: Medical treatment for hypertension.
timeFrame: Baseline, 3, 6 and 12 months
measure: Diagnosed with type 2 diabetes.
timeFrame: Baseline, 3, 6 and 12 months
Locations:
city: Kristiansand
country: Norway
facility: Sørlandet sykehus, Kristiansand
city: Levanger
country: Norway
facility: Levanger sykehus
city: Oslo
country: Norway
facility: Ullevål
city: Trondheim
country: Norway
facility: Kreftklinikken, St Olavs Hospital
city: Ålesund
country: Norway
facility: Ålesund sjukehus
Study officials:
affiliation: St. Olavs Hospital
name: Arne Solberg, md phd
role: STUDY_DIRECTOR
References:
citation: Hatlevoll I, Oldervoll LM, Wibe A, Stene GB, Stafne SN, Hofsli E. Physical exercise during adjuvant chemotherapy for colorectal cancer-a non-randomized feasibility study. Support Care Cancer. 2021 Jun;29(6):2993-3008. doi: 10.1007/s00520-020-05789-z. Epub 2020 Oct 8.