Monitoring and Telecoaching of Physical Activity in Patients With Stage III and IV Non-small Cell Lung Cancer
Phase: NA
Conditions: Exercise, Neoplasms
Sponsor: KU Leuven

 
 
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Protocol Full Title prospective observational trial: 
 
A prospective non-randomised control study to evaluate the efficacy of a physical activity 
promotion program on the experience of physical activity in patients with stage III and IV non-
small cell lung cancer (NSCLC) with objective response after initial treatment 
 
Protocol Acronym/short title: 
 
Monitoring and telecoaching of physical activity in patients with stage III and IV non-small cell 
lung cancer 
 
Version and date of final protocol: 
Version 5 amendment (15-03-2019).  
 
Sponsor: 
 
Name: UZLeuven 
Address: Herestraat 49, 3000 Leuven 
 
Principal Investigator: 
 
Name: Prof Janssens Wim 
Address: Herestraat 49, 3000 Leuven 
 
Telephone:  
Fax: 
Email: 
 
Sub-investigator: 
 
Name: Prof. Dr. Wauters Els, Prof. Dr. Dooms Christophe, Prof. Dr. Troosters Thierry, Dr. 
Demeyer Heleen, De Bent Kristien, Cardinaels Nina, Blondeel Astrid 
 
Address: Herestraat 49,3000 Leuven 
Telephone: 
Fax: 
Email: 
 
 
 

 
 
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Signatures 
 
 
 
_________________________ 
 
 
 
____________________ 
Principal Investigator 
 
 
 
 
Date 
 
 
Print Name: 
 
 
 
_________________________ 
 
 
 
____________________ 
 
 
 
 
 
 
 
 
Date 
 
 
Print Name: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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Table of Contents 
1. 
Study Synopsis ................................................................................................................................. 5 
2. 
Background and rationale ............................................................................................................... 8 
3. 
Trial objectives and Design .............................................................................................................. 9 
3.1 
Trial objectives..................................................................................................................... 9 
3.2 
Primary endpoints ............................................................................................................... 9 
3.3 
Secondary endpoints ........................................................................................................... 9 
3.4 
Exploratory endpoints ......................................................................................................... 9 
3.5 
Patient characterizing and safety measures ..................................................................... 11 
3.6 
Trial Design ........................................................................................................................ 11 
3.7 Study diagram .......................................................................................................................... 12 
3.8 
Trial Flowchart ................................................................................................................... 13 
4. 
Trial Medication (Trial intervention?) ........................................................................................... 14 
4.1 Investigational Medicinal product and dosing regimen .......................................................... 14 
4.2 Drug accountability ................................................................................................................. 14 
4.3 Subject compliance ................................................................................................................. 14 
4.4 Concomitant medication (non-IMP) ........................................................................................ 15 
5. 
Selection and withdrawal of subjects ........................................................................................... 15 
5.1 Inclusion criteria ...................................................................................................................... 15 
5.2 Exclusion criteria ..................................................................................................................... 15 
5.3 Selection of participants .......................................................................................................... 15 
5.4 Expected duration of trial ........................................................................................................ 17 
6. 
Trial Procedures ............................................................................................................................. 17 
6.1 
By visit................................................................................................................................ 17 
6.2 
Laboratory tests................................................................................................................. 18 
5.3 Other investigations ................................................................................................................ 18 
7. 
Assessment of efficacy .................................................................................................................. 18 
8. 
Assessment of Safety ..................................................................................................................... 18 
8.1 Specification, timing and recording of safety parameters ...................................................... 18 
8.2 Procedures for recording and reporting adverse events (AE) ................................................. 18 

 
 
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8.2.1 Definitions in Law of May 7, 2004 concerning experiments on the human person ............. 18 
8.2.2 Notification of adverse events .............................................................................................. 19 
8.2.3 Notification of serious adverse reactions ............................................................................. 19 
8.3 Treatment stopping rules ........................................................................................................ 20 
9. 
Statistics ........................................................................................................................................ 20 
9.1 Sample size .............................................................................................................................. 20 
9.2 Analysis .................................................................................................................................... 20 
10. 
Quality assurance ...................................................................................................................... 20 
11. 
Direct access to source data and documents ............................................................................ 20 
12. 
Ethics and regulatory approvals ................................................................................................ 21 
13. 
Data Handling ............................................................................................................................ 21 
14. 
Data Management ..................................................................................................................... 22 
15. 
Translational research ............................................................................................................... 22 
16. 
Publication Policy ...................................................................................................................... 22 
17. 
Insurance/Indemnity ................................................................................................................. 22 
18. 
Financial Aspects ....................................................................................................................... 22 
19. 
References ................................................................................................................................. 22 
 
 
 

 
 
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1. Study Synopsis  
 
 
Title of clinical trial 
 
 
A prospective non-randomised control study to evaluate 
the efficacy of a physical activity promotion program on 
the experience of physical activity in patients with stage 
III and IV non-small cell lung cancer (NSCLC) with 
documented disease control ( stable disease, partial 
response or complete response defined by RECIST V1.1) 
after initial treatment 
Protocol Short Title/Acronym 
 
 
 
Monitoring and telecoaching of physical activity in 
patients with stage III and IV non-small cell lung 
cancer  
 
Sponsor name 
 
 
UZ Leuven 
Principal Investigator 
 
 
Prof. Dr. Wim Janssens 
Medical condition or disease under 
investigation 
 
 Patients  with stage III and IV NSCLC with documented 
disease control (stable disease, partial or complete 
response defined by RECIST V1.1) at least 6 months after 
start of first line treatment. 
Purpose of clinical trial 
 
 
The objective of this pilot study is to investigate if 
physical activity can be improved by telecoaching in 
patients with advanced stages of lung cancer in 
remission. 
The physical activity telecoaching promotion program is a 
personalized, coaching program using  a direct 
measurement of physical activity to facilitate the semi-
automated coaching.  
 

 
 
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Primary objective 
 
 
To assess the impact of a telecoaching program on 
physical activity in patients with stage III and IV NSCLC in 
addition to usual care. This will be measured by the 
Dynaport movemonitor (Dynaport®), as the change in 
average daily number of steps at baseline (1 week 
preceding V3) and at the end (1 week preceding V4) in 
the intervention and the control group.  
Secondary objective (s) 
 
 
The secondary objectives are to assess: 
Change from baseline to 8 weeks in the coaching 
program and the control group in: 
 
 
Change in health status assessed by QLQ-C30 
(Cancer quality of life questionnaire) 
 
 
Change in exercise capacity by 6 minutes walking 
distance 
 
Exploratory outcomes: 
Change from baseline to 8 weeks in the coaching 
program and control group. 
 
 
Comparison of change between coaching and 
control group in number of daily steps, in health 
status assessed by QLQ-C30 and in 6 MWT 
 
Time spent in at least moderate intense physical 
activity 
 
Walking time and intensity of moving during 
walking 
 
Symptoms and difficulties perceived during 
exercise (Pro Active questionnaire) 
 
Health related quality of life as measured by 
SGRQ. 
 
Trial Design 
 
 
A prospective non-randomised control study 
Endpoints 
 
 
The amount of steps per day objectively measured with 
Dynaport Movemonitor after 8 weeks 

 
 
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Sample Size 
 
 
32 patients 
Summary of eligibility criteria 
 
 
Inclusion criteria: 
1. Patients diagnosed with stage III or stage IV 
NSCLC who have a documented disease control 
(stable disease, partial or complete response 
defined by RECIST V1.1) at least 6 months after 
start of first line treatment. Stage III patients can 
only be included, if first line treatment consisted 
of concurrent chemoradiotherapy and a 
consolidation immunotherapy if indicated (if 
PDL1 > 1% and no potential contraindications for 
immunotherapy). Stage IV patients, should have 
received only immunotherapy (PDL1 > 50%) or a 
treatment of at least 4 cycles of a platinum based 
chemotherapy. Maintenance therapy with 
chemotherapy and/or immunotherapy and 
administration of local radiotherapy is allowed.  
Patients with documented disease control can be 
included in the study until 2 years after starting 
up initial treatment.  
2. > 18 years         
3. Patients who are able to engage in a remote 
coaching program through the use of a 
smartphone 
 
Exclusion criteria: 
1. Patients actively participating in a pulmonary 
rehabilitation program 
2. Patients with sequential chemoradiotherapy for 
stadium III non-small cell lung cancer  
3. The presence of orthopedic problems not 
allowing an increase in PA levels 
 
Maximum duration of treatment of a 
Subject 
 
 
 
8 weeks 
Version and date of final protocol 
 
Version 5 (15-03-2019) 

 
 
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Version and date of protocol amendments 
 
Version 5 amendment 15-03-2019) 
 
2. Background and rationale 
 
Lung cancer has one of the highest mortality rates in both man and woman.1The most common type 
is non-small cell lung cancer (NSCLC).2,3 When diagnosed, most of the patients have an advanced 
stage of lung cancer, which are not eligible for a curative intervention and can only be treated by 
chemotherapy or biologicals.3,4 
A vast majority of patients with advanced lung cancer experiences various impairments resulting 
from symptoms of the disease (like dyspnoea, coughing, fatigue, appetite loss) and side effects from 
the treatment affecting their quality of life.5,6 Today, long-term remission in advanced lung cancer is 
more frequently reached by the new targeted tumor therapies, often at the cost of a pronounced 
inactive lifestyle. Physical inactivity negatively influences the symptom burden, quality of life and 
likely prognosis, and should therefore be considered as an individual therapeutic goal.7,8,9,10 Factors 
contributing to the level of physical activity in lung cancer include patient-level factors, such as 
symptoms, comorbidities, sedentary lifestyle, mood and fear, and environmental factors.11 
For patients with lung cancer, exercise can be of contributory value. It increases strength and 
endurance and reduces fatigue. It may also help to decrease emotional issues following the 
diagnosis lung cancer and to better tolerate symptoms of the disease and its treatments.9,12,13,14 
Whether a physical activity promotion program is effective  in improving daily physical activity and 
whether this improvement leads to changes in quality is not yet demonstrated.  
Stimulating home-based, low-intensity exercise monitored with a pedometer including behaviour 
strategies (goal setting, contracting, feedback, consequences and/or cues) has shown promising 
results to improve physical activity.15,16 Tele coaching  interventions are attractive tools in this regard 
allowing remote communication and individual feedback through electronic devices like a 
smartphone and improving quality of life by treating patients in their own home environment and 
providing patients with independence by having them play an active role in their own 
treatment.27,17,18,19,20 Furthermore it is less time consuming and a cost-effective solution compared to 
usual care.20,21,22 
A few studies have been done to investigate the effectiveness of tele coaching in patients with 
cancer or cancer survivors. These studies showed that tele coaching is significantly more effective in 
increasing and maintaining moderate physical activity compared to usual care in cancer 

 
 
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survivors.23,24,25,26 As far as we know, there are no studies that focussed on tele coaching for 
improving physical activity in patients with lung cancer in particular. As most of these patients are 
also suffering from COPD , in which these interventions have been proven extremely effective , there 
is an obvious need to develop such programs.  
The telecoaching program uses a previously developed coaching program, developed and validated 
by our research group in COPD patients.27 Briefly, the coaching will be facilitated by using a 
telecoaching system. Patients will be equipped with a step counter, which connects to a smartphone 
equipped with the needed coaching application.  
Data from the stepcounter collected on the smartphone device will be shared using ‘health care 
integrating information technology’. 
3. Trial objectives and Design 
3.1 Trial objectives 
The objective of this pilot study is to investigate if physical activity can be improved by telecoaching 
in patients with advanced stages of lung cancer in remission. We hypothesize that a smartphone 
application, designed for a population with respiratory symptoms, will increase daily physical 
activity, which translates into significant improvements on quality of life. This uncontrolled pilot 
study will therefore address if a 8-week PA promotion telecoaching program in addition to usual care 
has the potential to improve physical activity and quality of life in patients with lung cancer for a 
limited burden and at low cost. If so, a randomized controlled trial in a larger patient group can be 
envisaged.  
3.2 Primary endpoints 
To assess the impact of a telecoaching program on physical activity in patients with stage III and IV 
NSCLC with objective response (partial response or complete response defined by RECIST V 1.1) after 
initial treatment. This will be measured by the activity tracker (Dynaport movemonitor), as the 
change in average daily number of steps at baseline (1 week preceding V3) and at the end of the 
study (1 week preceding V4). 
3.3 Secondary endpoints 
1. Change in health status assessed by QLQ-C30 (Cancer quality of life questionnaire) 
2. Change in exercise capacity by 6 minutes walking distance 
3.4 Exploratory endpoints 
1. The time in at least moderate intense physical activity 
2. Walking time 
3. Intensity of moving during walking 

 
 
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4. Symptoms and difficulties perceived during exercise (clinical version of the PROactive tool, C-
PPAC)Active) 
5. Health related quality of life as measured by SGRQ (St. George's respiratory questionnaire) 
6. Change from baseline to 8 weeks between the telecoaching program and the control group 
in average daily number of steps, QLQ-C30 and 6 MWT. 
Activity monitor (Dynaport movemonitor) 
The Dynaport® is the activity monitor that will be used in this study. It will be carried one week prior 
to visit 3 and one week prior to visit 4. It is an electronic device that is used to measure the patient’s 
physical activity level (number of steps/day). The activity monitor provides valuable information of 
different aspects (i.e. different output parameters: time spent in at least moderate physical activity 
(MVPA), walking time, intensity of moving during walking, …) on physical activity, directly from the 
wearer, in real time and in real life. This monitor will be worn during the time patients are awake, 
and must not be worn during bathing or water sports activities. Mean daily step count has been 
chosen as primary outcome.  
 
Clinical version of the PROactive questionnaire (C-PPAC) 
The PROactive questionnaire investigates relevant dimensions of physical activity and is a PRO 
(patient reported outcome) tool that is developed for the measurement of physical activity in the 
daily life of COPD patients. The tool has 2 domain scores (difficulties experienced and experiences 
amount of PA) and a total score. We will use the clinical version of the PROactive tool, in which the 
responses are intended to reflect the patients experience over the preceding 7 days. Patients will 
complete the web-based version of this questionnaire on visit 3 and visit 4.  
 
QLQ-C30 (Cancer quality of life questionnaire) 
The QLQ-C30 is an internationally validated 30-item questionnaire assessing cancer-specific QOL. This 
widely used questionnaire comprises  five functional scales (physical, social, role, cognitive and 
emotional functioning), 3 symptom scales (fatigue, pain, nausea and vomiting), a global health 
status/QoL scale, and a number of single items assessing additional symptoms commonly reported 
by cancer patients (dyspnea, loss of appetite, insomnia, constipation and diarrhea) and perceived 
financial impacts of the disease. Each linear converted scale score ranges from 0 to 100. High scores 
for functional scales and for the global health status/QOL indicate better functioning, whilst high 
scores for symptom scales represent a higher level of symptom burden. 
 
The test takes about 10 minutes. A copy of the English version is attached in Appendix 1. 
SGRQ (St. George’s respiratory questionnaire) 
The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients 
with diseases of airway obstruction. Score are calculated for three domains: symptoms, activity and 
impacts (psycho-social) as well as a total score. A minimum change in score of 4 units was established 
as clinically relevant after patient and clinician testing. The SGRQ has been used in a range of disease 
groups including asthma, chronic obstructive pulmonary disease (COPD) and bronchiectasis. 
 

 
 
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The test takes about 25 minutes. A copy of the English version is attached in Appendix 1. 
 
Six minute walking test (6MWT) and Borg CR10 
All patients will undergo the Six minute walking test (6MWT). It is a reliable, valid and responsive 
outcome measure in patients with COPD and cancer patients. Patients will be asked to cover as much 
distance as possible in 6 minutes. The test will be carried out in accordance with ATS guidelines in a 
quiet corridor of at least 30 meters in length. Before and at the end of the test; heart rate, oxygen 
saturation and symptoms of dyspnea and fatigue (Borg scale CR 10) will be recorded. The result will 
be recorded and expressed as meters covered and as percentage of the predicted normal value. 
Patients will perform 2 six minute walking tests and the best of 2 tests will be retrieved.  
 
3.5 Patient characterizing and safety measures 
Patient characterizing: 
1. Baseline demographic data 
(date of birth and gender, medical/surgical history, COPD history (if applicable), smoking 
history, current medication, height and weight.) 
2. Lung function (Post bronchodilator spirometry, body plethysmography and diffusion 
capacity) 
3. Medical history including oncological stage, type and treatment. 
4. Co-morbidities based on self-report.  
Safety measures: 
Patients are asked to report any hospitalization and major medical events during the trial period. 
 
Lung function 
All lung function tests will be carried out according to ATS/ERS guidelines (Miller et al 2005) and post 
bronchodilator values will be recorded. 
 
3.6 Trial Design 
It will be a prospective non-randomised control study in which patients are evenly divided into the 
telecoaching group or usual care group according to owning a smartphone and their affinity with it. It 
is not possible to fully blind the investigator and patients. The trial will consist of 4 visits. An 
outpatient clinic visit (V1), a screenings visit (V2), a third visit (V3) at which the intervention will start 
and where the patients will be divided into the control or the intervention group and a final visit (V4) 
8 weeks after starting up the intervention (V4).  

 
 
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Patients in both groups will receive a brochure during V3 explaining the importance of physical 
activity with recommendations to improve it. This brochure will be discussed together with the 
patients.  
In the intervention group patients will receive the usual care in combination with the telecoaching 
intervention consisting of the following components: 1: motivational interview with the investigator 
during V3 discussing motivation, barriers, favourite activities and strategies to become more active; 
2: a pedometer giving direct feedback on the amount of steps; 3: the coaching application linked to 
the step counter, which will be installed on the patient’s smartphone. 4: telephone contact when a 
patient is non-compliant with either the use of the coaching intervention or with achieving the PA 
goals for 2 consecutive weeks. 
3.7 Study diagram
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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3.8 Trial Flowchart 
 
Visit 1 
Outpatient 
clinic 
Visit 2 
 Visit 3 
Visit 4 
Oncological check-up (CT/labo/…) 
demonstrating PR after initial 
treatment 
X 
 
 
 
Informed consent 
 
X 
 
 
Baseline demographic data 
 
X 
 
 
Medical history including 
oncological stage and type, co-
morbidities 
 
X 
 
 
Lung function 
X 
 
 
 
Instruction of the importance of 
PA (+ explanation on the 
intervention) 
 
 
X 
 
PA measurement by Dynaport 
movemonitor (measurement for 
7 consecutive days) 
 
 
X 
X 
Clinic version of the proactive 
questionnaire 
 
 
X 
X 
QLQ-C30 
 
 
X 
X 
6MWT 
 
 
X 
X 
SGRQ 
 
 
X 
X 
 
Legend: 
X routine clinical practice 
X Additional (study protocol) 

 
 
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X Indicate which tests are clinical routine in context of follow up after lung cancer treatment. All 
other tests are in context of study protocol and will be obtained by research staff. 
4. Trial intervention 
 
4.1 Investigational Medicinal product and dosing regimen 
 
Telecoaching intervention:  
The intervention group receives a step counter together with a coaching application installed on their 
smartphone. This application is a renewed version of the program used in a previous coaching trial, 
conducted by our research group (Demeyer 2017) and is based on the basic principles of behavioral 
change and contains four major domains. 
 
Motivational interviewing: 
A semi-structured interview is conducted to address barriers and enables to increase physical 
activity. Motivation and self-efficacy scores are asked to the patient.  
 
Step counter:  
The step counter gives direct feedback, expressed as amount of steps taken. Patient is instructed to 
wear this step counter every day, around the waist or wrist, as preferred. 
 
The coaching application:  
The coaching application, installed on the patient’s smartphone, shows a daily goal (expressed as 
amount of steps per day) to the patient. This start goal is individual and based on the physical activity 
level at the beginning of the coaching intervention. This goal is weekly revised and patients 
themselves are able to increase the goal every week with +500 of +1000 steps per day. 
Every evening, they are able to check the daily feedback platform, which gives them insights in their 
physical activity pattern of the day and previous weeks. Hereby they are able to evaluate their 
progression. At a regular basis, ‘tip of the day’ messages appear as a pop-up, to keep patients 
motivated. The last page of the application contains an action plan with activities discussed during 
the motivational interview in case there are difficulties to increase or maintain the physical activity 
levels.  
4.2 Drug accountability 
Not applicable. 
4.3 Subject compliance 
Not applicable. 

 
 
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4.4 Concomitant medication (non-IMP) 
Not applicable. 
5. Selection and withdrawal of subjects 
 
5.1 Inclusion criteria 
1. Patients diagnosed with stage III or stage IV NSCLC who have a documented disease control 
(stable disease, partial or complete response defined by RECIST V1.1) at least 6 months after 
start of first line treatment. Stage III patients can only be included, if first line treatment 
consisted of concurrent chemoradiotherapy and a consolidation immunotherapy if indicated (if 
PDL1 > 1% and no potential contraindications for immunotherapy). Stage IV patients, should 
have received only immunotherapy (PDL1 > 50%) or a treatment of at least 4 cycles of a platinum 
based chemotherapy . Maintenance therapy with chemotherapy and/or immunotherapy is 
allowed.  Administration of local radiotherapy is allowed. 
Patients with documented disease control can be included in the study until 2 years after starting 
up initial treatment. 
2. > 18 years 
3. Patients who are able to engage in a remote coaching program through the use of a smartphone 
3.1 Exclusion criteria 
1. Patients actively participating in a pulmonary rehabilitation program 
2. Patients with sequential chemoradiotherapy for stadium III non-small cell lung cancer  
3. The presence of orthopedic problems not allowing an increase in PA levels 
5.3 Selection of participants 
Patients will be screened for inclusion in the study during follow up visits in the outpatient lung 
cancer clinic at visit 1 (outpatient clinic).  
Patients with stage III or stage IV NSCLC are included in the study if they have a documented 
objective partial or complete response (defined by RECIST V 1.1) around 6 months after start of first 
line treatment. 
Stage III patients can only be included, if first line treatment consisted of concurrent 
chemoradiotherapy and a consolidation immunotherapy if indicated (if PDL1 > 1% and no potential 
contraindications for immunotherapy). 
Stage IV patients, should have received only immunotherapy (PDL1 > 50%) or a treatment of at least 
4 cycles of a platinum based chemotherapy. Maintenance therapy with chemotherapy or 
immunotherapy is allowed. The indication to start immunotherapy or chemotherapy will be 
discussed case by case based on a multidisciplinary discussion (Molmoc). (cfr figure 1) 

 
 
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Figure 1:
 

 
 
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5.4 Expected duration of trial 
Patients will be coached for 8 weeks. A screening period of 1-2 weeks before makes a trial duration 
of maximum 10 weeks for this pilot study. We expect to start January 2019.  
1. Trial Procedures 
6.1 By visit 
Describe the sequence of procedures to be performed at each visit as detailed in the time/event 
flowchart in section 3.6. 
Visit 1 (outpatient clinic) 
Patients will be screened for inclusion in the study during follow up visits in the outpatient lung 
cancer clinic.  If oncological check-up after starting initial lung cancer treatment( with CT thorax 
upper abdomen, CT-brain, …) demonstrates documented disease control ( stable, partial or complete 
response defined by RECIST V1.1) the patient is asked to join the study. If the patient wants to join 
the study a screening visit (V2) will be planned. Patients  with documented disease control can be 
included in the study until 2 years after starting up initial treatment.  
Visit 2 (screening visit (run-in)) 
During visit 2 (run-in) all eligible patients who have signed the informed consent will enter the run in 
epoch of 1 to 2 weeks. 
Patients are asked about their medical history (baseline demographic data) and their previous 
respiratory treatment including their oncological stage and type. Co-morbidities will also be assessed 
and a basic lung function will be performed. 
On visit 2 patient will receive a Dynaport movemonitor to wear one week before visit 3. For patients 
where the run in period is more than one week, they will receive a telephone reminder to wear 
PROactive monitors. Patients are instructed to wear the device during waking hours. A measurement 
of more than 8 hours of wearing time will be defined as a ‘valid day). The tri-axial accelerometer will 
captured steps waked per day, movement intensity and time spent in sitting, lying walking and high-
intense activities.  
Visit 3 (baseline, allocation)  
Patients will complete the web-based version of the clinical visit of the PROactive questionnaire. Two 
six-minutes walk tests will be performed and the patient will complete the quality of life 
questionnaires. During visit 3, the patients are divided into either control (usual care) or telecoaching 
group based on personal preferences and the abilities of using and having a smartphone. 
All patients will be equipped with the Dynaport movemonitor one week before visit 4 and will be 
instructed to wear the monitor for 7 consecutive days.  
 

 
 
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Visit 4 (end of the study, 8 weeks post allocation) 
Visit 4 is the end of the study.  All assessments performed on visit 3 will be repeated during this study 
visit.  
 
6.2 Laboratory tests 
Not applicable. 
5.3 Other investigations 
Not applicable. 
7 Assessment of efficacy 
 
The efficacy of the intervention will primary be assessed with an activity monitor worn for one week 
at baseline and after 8 weeks of intervention. 
 
8 Assessment of Safety 
8.1 Specification, timing and recording of safety parameters 
If problems occur during the trial period, patients are asked to contact the investigator to discuss the 
possible adverse events. If necessary, an extra visit or consultation with a physician will be scheduled. 
 
8.2 Procedures for recording and reporting adverse events (AE) 
8.2.1 Definitions in Law of May 7, 2004 concerning experiments on the human person 
 
Adverse reaction (AR): all untoward and unintended responses to an investigational medicinal 
product or to an experiment and, when an investigational product is concerned, related to any dose 
administered;  
Adverse event (AE): any untoward medical occurrence in a patient or subject of the treated group 
during an experiment, and which does not necessarily have a causal relationship with this treatment; 
Unexpected adverse reaction (UAR): an adverse reaction, the nature or severity of which is not 
consistent with the information on the experiment, and, when a clinical trial is concerned, with the 
applicable product information (e.g. investigator's brochure for an unauthorized investigational 

 
 
Page 19 of 33 
 
 
product or the patient leaflet joined to the summary of product characteristics for an authorized 
product); 
Serious adverse event (SAE) or serious adverse reaction (SAR): any untoward medical occurrence or 
effect that results in death, is life-threatening, requires hospitalisation or prolongation of existing 
hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly 
or birth defect, and this, when it is a clinical trial, at any dose;  
Suspected unexpected serious adverse reaction (SUSAR): is an AR that  is serious and unexpected 
(meaning that nature or severity of the AR is not consistent with the Investigational Medicinal 
Product reference safety information, which is the Investigator’s Brochure) and is judged by either 
the investigator or the sponsor as having a reasonable suspected causal relationship with the 
investigational medicinal product.  
 
8.2.2 Notification of adverse events 
 
The investigator shall report all serious adverse events immediately, after first knowledge, to the 
sponsor except for those that the protocol or investigator's brochure identifies as not requiring 
immediate reporting. The immediate report shall be followed by detailed, written reports. The 
immediate and follow-up reports shall identify subjects by code numbers.  
For reported deaths of a subject, the investigator shall supply the sponsor and the accredited ethics 
committee with any additional information requested. 
The sponsor shall keep detailed records of all adverse events which are reported to him by the 
investigator or investigators. These records shall be submitted to the minister if the experiment is 
being conducted in Belgium, if he so requests. 
 
8.2.3 Notification of serious adverse reactions 
 
The sponsor shall ensure that all relevant information about suspected unexpected serious adverse 
reactions that are fatal or life-threatening is recorded and reported as soon as possible to the 
minister, to the competent authorities in all the Member States concerned in the case of a trial, and 
to the competent ethics committee, and in any case no later than seven days after knowledge by the 
sponsor of such a case, and that relevant follow-up information is subsequently communicated 
within an additional eight days. 
All other suspected unexpected serious adverse reactions shall be reported to the minister, to the 
competent authorities of all Member States concerned in the case of a clinical trial and to the ethics 
committee concerned as soon as possible but within a maximum of fifteen days of first knowledge by 
the sponsor. 

 
 
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The sponsor shall also inform the other investigators. 
Once a year throughout the experiment, the sponsor shall provide the minister and the ethics 
committee in Belgium and those of the member States in whose territory the trial is conducted in the 
case of a multicentre trial, with a listing of all suspected serious adverse reactions which have 
occurred over this period and a report of the subjects' safety. 
Regarding those adverse events and serious adverse reactions the Principal Investigator will take all 
reasonable measures, in consultation with Sponsor, to protect subjects at risk following the 
occurrence of such events. 
8.3 Treatment stopping rules 
Not applicable. 
9 Statistics 
9.1 Sample size 
We will include 16 patients motivated for a coaching program and compare them with a matched 
control group of 16 patients receiving usual care. As this pilot study is underpowered to detect 
between group differences at the end of the intervention, we will base our primary analysis on the 
within group difference of the intervention group. Based on an anticipated pre-post difference of 
1500 steps/day and a SD of 2000 steps/day, we need 16 individuals for a power of 80% using an α 
level of 0.05 (two-sided, paired T test).  The control group will be used to address the repeatability of 
the activity measures. Both groups will be needed for a power calculation of the subsequent 
randomized trial. 
9.2 Analysis 
Within group comparison of the primary and secondary outcome parameters will be analyzed by 
paired T-test statistics for parametric distributions and Wilcoxon signed-rank test test for non-
parametric distributions. Linear and logistic regression will be used to address determinants of 
treatment response. Ancova analyses will be used to compare between group differences at 8 weeks, 
adjusted for baseline  differences and possible confounders. Data will be presented as mean ± SD. 
Statistical significance will be set at p<0.05 for all the analyses.  
10 Quality assurance 
The study team performs the tests in a standardized way, according to the guidelines. The research 
group is familiar with the telecoaching intervention and motivational interviewing due to internal 
courses and previous studies.  
11 Direct access to source data and documents 
It will be specified, (or reference is made to another written agreement) that the investigator(s) and 
the institution(s) will permit trial-related monitoring, audits, EC review, and regulatory inspections 

 
 
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(where appropriate) by providing direct access to source data and other documents (ie patients’ case 
sheets, blood test reports, X-ray reports, histology reports etc).  
12 Ethics and regulatory approvals 
The trial will be conducted in compliance with the principles of the Declaration of Helsinki 
(current version), the principles of GCP and in accordance with all applicable regulatory 
requirements. This protocol and related documents will be submitted for review to Ethics 
Committee and to the Federal Agency for medicinal products for Clinical Trial Authorisation. 
The Study can and will be conducted only on the basis of prior informed consent by the 
Subjects, or their legal representatives, to participate in the Study. The Participating Site shall 
obtain a signed informed consent form (ICF) for all patients prior to their enrollment and 
participation in the Study in compliance with all applicable laws, regulations and the approval of 
the (local) Ethics Committee, if required. The Participating Site shall retain such ICFs in 
accordance with the requirements of all applicable regulatory agencies and laws. 
The Investigator and the Participating Site shall treat all information and data relating to the 
Study disclosed to Participating Site and/or Investigator in this Study as confidential and shall 
not disclose such information to any third parties or use such information for any purpose other 
than the performance of the Study. The collection, processing and disclosure of personal data, 
such as patient health and medical information is subject to compliance with applicable 
personal data protection and the processing of personal data (the patients’ rights are 
guaranteed by the European Data Protection Regulation (GDPR), by the Belgian legislation on 
the protection of natural persons with regard to the processing of personal data and by the Law 
of 22 August 2002 on patient rights). 
Data are anonymous if no one, not even the researcher, can connect the data to the individual 
who provided it. No identifying information is collected from the individual. 
When data are coded, there continues to be a link between the data and the individual who 
provided it. The research team is obligated to protect the data from disclosure outside the 
research according to the terms of the research protocol and the informed consent document. 
The subject’s name or other identifiers should be stored separately from their research data and 
replaced with a unique code to create a new identity for the subject. Note that coded data are 
not anonymous. 
The present study will use coded data after giving a unique study identifier to each included 
subject.  
13 Data Handling 
Data will be coded and collected in a excel database, and will be saved on the KU Leuven server. 

 
 
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14 Data Management 
Data will be collected on paper and electronically in an excel database. This will be saved on the KU 
Leuven server. 
15 Translational research 
Not applicable. 
16 Publication Policy 
 
Not applicable. 
17 Insurance/Indemnity 
In accordance with the Belgian Law relating to experiments on human persons dated May 7, 2004, 
Sponsor shall assume, even without fault, the responsibility of any damages incurred by a Study 
Patient and linked directly or indirectly to the participation to the Study, and shall provide 
compensation therefore through its insurance. 
18 Financial Aspects 
All tests related to the study will be performed by the study team and covered by the budget of the 
research group.  There will be no compensation for patients who decide to enter the study. Every 
patients receives a free parking ticket per visit.  
19 References 
1. Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9-29.  
2. Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. 
Translational Lung Cancer Research. 2016;5(3):288-300. 
 
3. Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. 
Clin Chest Med. 2011;32(4):605-44. 
4. Oncoline.nl. Behandeling stadium IV NSCLC. https://www.oncoline.nl/niet-kleincellig-
longcarcinoom. Updated December 18, 2015. Assessed june 27, 2018. 
 
5. Johnsen AT, Petersen MA, Pedersen L, Groenvold M. Symptoms and problems in a nationally 
representative sample of advanced cancer patients. Palliat Med. 2009;23(6):491–501. 
6. Thompson E, Sola I, Subirana M. Non-invasive interventions for improving well-being and 
quality of life in patients with lung cancer–a systematic review of the evidence. Lung Cancer. 
2005;50(2):163–76. 

 
 
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7. Lee IM, Shiroma EJ, Lobelo F, et al. Effect of physical inactivity on major non-communicable 
diseases worldwide: an analysis of burden of disease and life expectancy. Lancet. 
2012;380:219–29. 
8. Kraus WE, Bittner V, Appel L, et al. The National Physical Activity Plan: a call to action from 
the American Heart Association: a science advisory from the American Heart Association. 
Circulation. 2015;131:1932–40. 
 
9. Fong DY, Ho JW, Hui BP et al. Physical activity for cancer survivors: meta-analysis of 
randomised controlled trials. Br Med J. 2012; 344: e70. 
10. Lee IM. Physical activity and cancer prevention — Data from epidemiologic studies. Med Sci 
Sports Exerc. 2003;35(11):1823–1827. 
 
11. Granger CL, Connolly B, Denehy L, Hart N, Antippa P, Lin KY, Parry SM. Understanding 
factors influencing physical activity and exercise in lung cancer: a systematic review. Support 
Care Cancer. 2017;25(3):983-999. 
 
12. Michaels C. The importance of exercise in lung cancer treatment. Translational Lung Cancer 
Research. 2016;5(3):235-238.  
 
13. Kuehr L, Wiskemann J, Abel U, et al. Exercise in patients with non-small cell lung cancer. 
Med Sci Sports Exerc 2014;46:656-63.  
 
14. Cramp F, Daniel J. Exercise for the management of cancer-related fatigue in adults. 
Cochrane Database Syst Rev. 2008;(2):CD006145. 
15. Brett C. Bade, MD, D. David Thomas, MS, JoAnn B. Scott, BA, and Gerard A. Silvestri, MD, 
MS. Increasing Physical Activity and Exercise in Lung Cancer J Thorac Oncol. 2015;10: 861–
871. 
 
16. Conn VS, Hafdahl AR, Brown SA, et al. Meta-analysis of patient education interventions to 
increase physical activity among chronically ill adults. Patient Educ Couns. 2008;70:157–72. 
17. Glynn LG, Hayes PS, Casey M, et al. Effectiveness of a smartphone application to promote 
physical activity in primary care: the SMART MOVE randomised controlled trial. The British 
Journal of General Practice. 2014;64(624):e384-e391.  
 
18. Field MJ, Institute of Medicine CoECAoT. Telemedicine: a guide to assessing 
telecommunications in health care. Washington DC: National Academy Press. 1996. 
 
19. Cox A, Lucas G, Marcu A, et al. Cancer Survivors’ Experience With Telehealth: A Systematic 
Review and Thematic Synthesis. Eysenbach G, ed. Journal of Medical Internet Research. 
2017;19(1):e11.  
 
20. McCue M, Fairman A, Pramuka M. Enhancing quality of life through telerehabilitation. Phys 
Med Rehabil Clin North Am. 2010;21:195-205. 
21. Grustam AS, Severens JL, De Massari D, Buyukkaramikli N, Koymans R, Vrijhoef HJM. Cost-
Effectiveness Analysis in Telehealth: A Comparison between Home Telemonitoring, Nurse 

 
 
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Telephone Support, and Usual Care in Chronic Heart Failure Management. Value Health. 
2018;21(7):772-782. 
 
22. Delgoshaei B, Mobinizadeh M, Mojdekar R, Afzal E, Arabloo J, Mohamadi E. Telemedicine: A 
systematic review of economic evaluations . Medical Journal of the Islamic Republic of Iran. 
2017;31:113.  
 
23. Kanera IM, Willems RA, Bolman CAW, Mesters I, Verboon P, Lechner L. Long-term effects of 
a web-based cancer aftercare intervention on moderate physical activity and vegetable 
consumption among early cancer survivors: a randomized controlled trial. The International 
Journal of Behavioral Nutrition and Physical Activity. 2017;14:19.  
 
24. Galiano-Castillo N, Cantarero-Villanueva I, Fernández-Lao C, Ariza-García A, Díaz-Rodríguez 
L, Del-Moral-Ávila R, Arroyo-Morales M. Telehealth system: A randomized controlled trial 
evaluating the impact of an internet-based exercise intervention on quality of life, pain, muscle 
strength, and fatigue in breast cancer survivors. Cancer. 2016;122(20):3166-3174. 
25. Galiano-Castillo N, Arroyo-Morales M, Lozano-Lozano M, Fernández-Lao C, Martín-Martín L, 
Del-Moral-Ávila R, Cantarero-Villanueva I. Effect of an Internet-based telehealth system on 
functional capacity and cognition in breast cancer survivors: a secondary analysis of a 
randomized controlled trial. Support Care Cancer. 2017;25(11):3551-3559. 
 
26. Eakin EG, Lawler SP, Winkler EA, Hayes SC. A randomized trial of a telephone-delivered 
exercise intervention for non-urban dwelling women newly diagnosed with breast cancer: 
exercise for health. Ann Behav Med. 2012 Apr;43(2):229-38. 
 
27. Demeyer H, Louvaris Z, Frei A, Rabinovich RA, de Jong C, Gimeno-Santos E, Loeckx M, 
Buttery SC, Rubio N, Van der Molen T, Hopkinson NS, Vogiatzis I, Puhan MA, Garcia-
Aymerich J, Polkey MI, Troosters T; Mr Papp PROactive study group and the PROactive 
consortium. Physical activity is increased by a 12-week semiautomated telecoaching 
programme in patients with COPD: a multicenter randomised controlled trial. Thorax. 2017 
May;72(5):415-423.  
 
 
 
 
 
 
 
 
 
 

 
 
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Appendix 1 
1.1 Clinical version of the PROactive questionnaire (C-PPAC) 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
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1.2 QLQ-C30 (Cancer quality of life questionnaire) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1.3  
 
 
 

 
 
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SGRQ (St. George’s respiratory questionnaire) 
 
 
 
 

 
 
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