Clinical trial NCT02473003: Physical Training and Cancer-a Multicenter Clinical Trial
Official title: Physical Training and Cancer- Effects and Understanding of Mechanisms for Prevent and Minimizing Cancer Related Fatigue, Improve Quality of Life and Disease Outcome
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Breast Cancer
Colorectal Cancer
Prostate Cancer
Keywords: Breast cancer
prostate cancer
colorectal cancer
fatigue
physical exercise
randomised trial
intervention
Lead sponsor: Uppsala University
Sponsor class: OTHER
Collaborators: name: The Swedish Research Council
name: Swedish Cancer Society
name: Nordic Cancer Union
name: Linkoeping University
name: Lund University
name: University of Agder
name: Copenhagen University Hospital, Denmark
name: Norwegian School of Sport Sciences
name: Amsterdam UMC, location VUmc
name: University of Amsterdam
name: University of Leeds
First posted: 2015-06-16
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Excessive tiredness (fatigue) is a common problem in cancer patients and can affect quality of life negatively. There is limited knowledge about the physical mechanisms that cause fatigue, and there is no medical treatment. Physical activity can reduce the inconvenience, but the investigators need to learn more about the type and intensity of exercise that works the best as well as how to motivate patients to exercise. The overall aim, is to evaluate the efficacy and cost-effectiveness of individually tailored high (H) and low/medium (LM) intensity physical training, with or without behavioural medicine (BM) support strategies, during adjuvant oncological treatment on; Cancer Related Fatigue (CRF),Quality of Life (QoL), mood disturbance, adherence to the cancer treatment, adverse effects, disease outcome, return to a daily life after completed treatment and return to work. The investigators will also describe changes in inflammatory markers and cytokines related to physical training and gene expressions following training to investigate whether these serve as mediators for the effects of physical training on CRF and QoL. This will be evaluated in newly diagnosed breast, colorectal and prostate cancer patients during adjuvant therapy at three different centres in Sweden; Uppsala, Lund/Malmö and Linköping. A 2x2 factorial design will be used, 600 patients will be randomised to H, H+BM, LM or LM+BM. Patients will train two times per week during 6 months. This project will give; new knowledge about aspects for individuals to gain improved well-being and quality of life, facilitated return to work, and possibly reduced risk of cancer recurrence. This in turn would result in lower burden on the health care system, reduced societal costs and have a positive impact on public health. Implementation of the results into clinical practice will be facilitated by the close collaboration between researchers and clinicians, and the fact that the study is performed in clinical settings.

Detailed description: Purpose and Aims The main aim is to determine the effects of high or low intensity physical training with or without integrated behavioral medicine support strategies to prevent and minimize cancer related fatigue (CRF), improve health related quality of life (QoL) and to understand the role of inflammation and cytokines in the development and maintenance of CRF, as well as to increase knowledge with respect to cost-effectiveness of rehabilitation programs. This will be evaluated in newly diagnosed breast, colorectal and prostate cancer patients during adjuvant therapy at three different centers in Sweden; Uppsala, Lund/Malmö and Linköping and one in Norway.

More specifically, the investigators' objectives are to:

1. Investigate the effects of high intensity training compared to low intensity training on patient reported outcomes (CRF as primary endpoint), chemotherapy/radiation completion rates, medical (oncology) adverse effects, physical activity and daily function, during adjuvant treatment and at long-term-follow up. In addition, effects on the course of disease (e.g time to relapse).
2. Investigate if supplemental behavioural medicine support strategies increase adherence to exercise during adjuvant therapy and further if they increase the maintenance of physical activity behaviours and decrease sedentary time in the long run.
3. Explore the role of changes in inflammatory markers and cytokines related to physical training and following training to investigate whether these serve as mediators for the effects of physical training on CRF and QoL.
4. Pursue the investigation of a direct role of cytokines secreted from the working muscles, in inhibiting cancer cell growth and inducing apoptosis.
5. Evaluate health economic issues; cost effectiveness of the interventions, health production and individual wellbeing.

In Phys-Can, the investigators will implement rigorously designed and adequately powered randomized longitudinal multicenter clinical trials, with physical training and behavioral medicine support interventions. The highly multi- and interdisciplinary and international consortium behind this proposal is in an excellent position to perform international and interdisciplinary competence- and network-building activities to generate valid, high quality data covering all areas included in the project, from basic biomedical data to patient reported outcomes (PROs), i.e. from bench to bedside. This is unique in health care sciences.

Study design A 2x2 factorial design will be used. With this design the investigators can study main effects and interactions between factors (groups). Patients will be randomized to one of the following groups; A) individually tailored high intensity training twice a week with (H+BM) or without behavioral medicine support strategies (H) or B) individually tailored low intensity training twice a week with (L+BM) or without behavioral medicine support strategies (L).

Study sample/procedure Patients, who are recently diagnosed with breast cancer, colorectal cancer or prostate cancer and scheduled for adjuvant therapy at Uppsala, Lund/Malmö, Linköping and Haukeland University hospitals will be consecutively included in the study. Based on the power calculation, 612 patients will be included.

All patients will exercise twice a week during 6 months which is equal to the most extensive adjuvant treatment period. It is also an optimal period to achieve physical training effects and to establish physical activity behavior. Physical training under the guidance of trained coaches will be offered twice a week. Training intensity is 40-50% (low intensity group) or 80-90% (high intensity group) of maximal cardiorespiratory fitness/muscular strength. Physical training sessions consist of both cardiorespiratory and resistance exercise. Every four week, progress from resistance training is evaluated by means of a strength test, and absolute intensity is adjusted accordingly Motivational and self-regulatory behavioral medicine support strategies (motivational and self-regulatory strategies) will be provided for the H+BM and the L+BM groups i.e. strategies to enhance engagement in the high and low intensity exercise programs respectively, and to maintain health enhancing physical activity after the completion of the programs.

Eligibility criteria: Inclusion Criteria:

* understand and talk Swedish.
* patients with breast cancer who receive neoadjuvant / adjuvant chemotherapy and / or adjuvant radiotherapy and / or adjuvant endocrine treatment.
* patients with colorectal cancer who receive adjuvant chemotherapy.
* patients with prostate cancer who receive neoadjuvant / adjuvant endocrine treatment with the addition of curative radiation therapy.

Exclusion Criteria:

* Patients unable to perform basic activities of daily living.
* Patients with cognitive disorders such as dementia and severe psychiatric illness.
* Patients with disabilities that may prevent physical activity: (eg, unstable angina, heart failure, chronic obstructive pulmonary disease, orthopedic and neurological diseases).
* Breast cancer stage IIIb.
* Undergoing treatment for other types of malignant disease.

Primary outcomes:
measure: Change in Fatigue
timeFrame: post oncol treatment (expected time frame 6-8 weeks), 6 month, 1,2,5 years
Secondary outcomes:
measure: Change in Quality of Life
timeFrame: post oncol treatment (expected time frame 6-8 weeks), 6 month, 1,2,5 years
measure: Change in Mood disturbance
timeFrame: post oncol treatment (expected time frame 6-8 weeks), 6 month, 1,2,5 years
measure: Change in Function in Daily life
timeFrame: 6 months,1, 2, 5 years
measure: Change in pain
timeFrame: post oncol treatment (expected time frame 6-8 weeks), 6 month, 1,2,5 years
measure: Change in Cardio respiratory fitness
timeFrame: 6 month
measure: Change in Muscle strength
timeFrame: 6 months
measure: Health Economy
timeFrame: 12 months
measure: Cancer recurrence
timeFrame: 10 year
measure: Sleep
timeFrame: 6 months
measure: Health Economy register
timeFrame: 12 months
measure: Cancer recurrence
timeFrame: 6 months, 1, 2, 5, 10 years
measure: Treatment completion rate
timeFrame: 1, 2, 5, 10 year
Other outcomes:
Locations:
Study officials:
affiliation: Uppsala University
name: Karin Nordin, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schauer T, Henriksson A, Strandberg E, Lindman H, Berntsen S, Demmelmaier I, Raastad T, Nordin K, Christensen JF. Pre-treatment levels of inflammatory markers and chemotherapy completion rates in patients with early-stage breast cancer. Int J Clin Oncol. 2023 Jan;28(1):89-98. doi: 10.1007/s10147-022-02255-0. Epub 2022 Oct 21.
citation: Brooke HL, Mazzoni AS, Buffart LM, Berntsen S, Nordin K, Demmelmaier I. Patterns and determinants of adherence to resistance and endurance training during cancer treatment in the Phys-Can RCT. BMC Sports Sci Med Rehabil. 2022 Aug 13;14(1):155. doi: 10.1186/s13102-022-00548-5.
citation: Mazzoni AS, Brooke HL, Berntsen S, Nordin K, Demmelmaier I. Effect of self-regulatory behaviour change techniques and predictors of physical activity maintenance in cancer survivors: a 12-month follow-up of the Phys-Can RCT. BMC Cancer. 2021 Nov 25;21(1):1272. doi: 10.1186/s12885-021-08996-x.
citation: Schauer T, Mazzoni AS, Henriksson A, Demmelmaier I, Berntsen S, Raastad T, Nordin K, Pedersen BK, Christensen JF. Exercise intensity and markers of inflammation during and after (neo-) adjuvant cancer treatment. Endocr Relat Cancer. 2021 Mar;28(3):191-201. doi: 10.1530/ERC-20-0507.
citation: Mazzoni AS, Brooke HL, Berntsen S, Nordin K, Demmelmaier I. Exercise Adherence and Effect of Self-Regulatory Behavior Change Techniques in Patients Undergoing Curative Cancer Treatment: Secondary Analysis from the Phys-Can Randomized Controlled Trial. Integr Cancer Ther. 2020 Jan-Dec;19:1534735420946834. doi: 10.1177/1534735420946834.
citation: Johnsson A, Demmelmaier I, Sjovall K, Wagner P, Olsson H, Tornberg AB. A single exercise session improves side-effects of chemotherapy in women with breast cancer: an observational study. BMC Cancer. 2019 Nov 8;19(1):1073. doi: 10.1186/s12885-019-6310-0.
citation: Berntsen S, Aaronson NK, Buffart L, Borjeson S, Demmelmaier I, Hellbom M, Hojman P, Igelstrom H, Johansson B, Pingel R, Raastad T, Velikova G, Asenlof P, Nordin K. Design of a randomized controlled trial of physical training and cancer (Phys-Can) - the impact of exercise intensity on cancer related fatigue, quality of life and disease outcome. BMC Cancer. 2017 Mar 27;17(1):218. doi: 10.1186/s12885-017-3197-5.