Lung Cancer Rehabilitation After Medical Treatment

Lung Neoplasms Clinical Trial

Official title:

The Effectiveness of Rehabilitation for Patients With Lung Cancer in China: a Randomised Controlled Trial

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT04185467
• Other study ID #: NantongU
• Status: Suspended
• Phase: N/A
• Start date: December 5, 2019
• Est. completion date: December 1, 2021

Study information

• Verified date: April 2020
• Source: Nantong University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lung cancer is the leading cause of cancer death worldwide and associated with high disease burden, symptoms and poor health-related quality of life (HRQoL). Lung cancer is the most commonly diagnosed type of cancer in China (with rates rising due to the smoking incidence) and is the leading cause of cancer-related death. The burden is on patients, families, the healthcare system and society, and will continue to rise into the future. The full impact of this in China has not yet occurred. New strategies are urgently required to improve survivorship. This multi-site, assessor blinded, two-arm superiority randomised controlled trial, conducted at two hospitals in China, aims to test the effect of exercise rehabilitation, compared to usual care (no exercise rehabilitation) on HRQoL and functional outcomes in 150 patients treated for lung cancer. The primary hypothesis is that exercise rehabilitation will be superior to usual care, in improving HRQoL at 12-weeks (post program). Secondary aims include measuring the effectiveness of exercise rehabilitation, compared to usual care on function, physical activity, symptoms, mood, sleep and program costs. Faecal samples (500mg) will be collected before and after the intervention.

Description:

Lung cancer is the leading cause of cancer death worldwide and associated with high disease burden, symptoms and poor health-related quality of life (HRQoL). Lung cancer is the most commonly diagnosed type of cancer in China (with rates rising due to the smoking incidence) and is the leading cause of cancer-related death. The burden is on patients, families, the healthcare system and society, and will continue to rise into the future. The full impact of this in China has not yet occurred. New strategies are urgently required to improve survivorship. This multi-site, assessor blinded, two-arm superiority randomized controlled trial, conducted at two hospitals in China, aims to test the effect of exercise rehabilitation, compared to usual care (no exercise rehabilitation) on HRQoL and outcomes including physical function in 150 patients treated for lung cancer. The primary hypothesis is that exercise rehabilitation will be superior to usual care, in improving HRQoL at 12-weeks (post program). Secondary aims include include measuring the effectiveness of exercise rehabilitation, compared to usual care on function, physical activity, symptoms, mood, sleep and program costs.

One hundred and fifty patients with stage I-IIIA non-small cell lung cancer (NSCLC) 4-12 weeks following completion of treatment (including surgery with or without adjuvant therapy) and life expectancy greater than 6 months will be recruited from the affiliated hospital of Nantong University and the first affiliated hospital of Nanjing Medical University. At recruitment participants provide written informed consent, complete baseline assessment and to ensure concealment of allocation participants will be randomly allocated off-site to one of two arms (1:1 ratio). The intervention programs start following randomization and will continue for 12 weeks duration. Trained physiotherapists will provide the intervention. Patients in both arms will receive usual medical, physiotherapy and nursing care according to usual protocols. This does not involve exercise rehabilitation or advice. Additionally patients in intervention group (exercise rehabilitation) will receive a multimodal program which includes a 90 minute program at the hospital gymnasium in a supervised environment a minimum of once but up to twice per week. Rehabilitation will include aerobic (brisk walking) and resistance training and 30 minutes of 8 style Tai Chi). Participants will be advised to walk on days of non-attendance - this will be individualized with the aim to have participants increase to 30 minutes walking per day. Assessments will be conducted at baseline and then by blinded assessors at 12 weeks and 6 months post-baseline. Survival will be followed-up and censored at 1 year. This important study brings together a strong collaborative research team spanning China and Australia, involving medical doctors, physiotherapists and academics. The topic is important, novel and will generate clinically meaningful research for an international audience, aiming to improve the survivorship quality of patients with lung cancer.

The gut microbiome is a source of potentially disease-modifying bioactive metabolites and has recently been suggested to contribute to the pathogenesis of a variety of disorders. Therefore, we will study the gut microbiota and metabolites of the participants in order to identify potential the biomarkers for the clinical outcomes. Fresh faecal samples will be collected from all individuals before group assignment and after the completion of the program. The written informed consent will be provided by the participants.

Specifically, faecal samples (500mg) will be collected from participants who are free from gastrointestinal conditions, with no antibiotic exposure in the 28 days prior to sample collection. 'Snap' frozen samples will be stored at -80°C until the time of DNA extractions, 16S rDNA sequencing, and mass spectrometry analysis of the faecal metabolites. The distribution of gut microbiota before and after exercise will be compared and analyzed to obtain the species of bacterial flora that changed significantly after exercise. Moreover, the gut metabolites that changed significantly before and after exercise will be used to explore the biomarkers for the curative effect of rehabilitation exercise, as well as their relationships with the differentially distributed gut microbiota.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 150
• Est. completion date: December 1, 2021
• Est. primary completion date: February 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients with non-small cell lung cancer (NSCLC) 4-12 weeks following completion of treatment (surgery, chemotherapy, radiotherapy, immunotherapy);

2. Physician/doctor approval;

3. Physician rated life expectancy greater than 6 months;

4. Informed consent;

5. Eastern Cooperate Oncology Group (ECOG) performance status of 0-2 at study entry;

6. Not meeting physical activity/exercise guidelines.

Exclusion Criteria:

1. Unstable psychiatric/cognitive disorder;

2. Comorbidity preventing exercise;

3. ECOG performance status of 3 or 4 at study entry.

Related Conditions & MeSH terms

• Lung Neoplasms

Intervention

Other:
• Intervention (rehabilitation exercise)
Patients in intervention group (exercise rehabilitation) will receive a multimodal program which includes a 90 minute program at the hospital gymnasium in a supervised environment a minimum of once but up to twice per week. Rehabilitation will include aerobic (brisk walking), resistance training and 30 minutes of 8 style Tai Chi. Participants will be advised to walk on days of non-attendance - this will be individualised with the aim to have participants increase to 30 minutes walking per day.

Locations

Country	Name	City	State
China	The First Affiliated Hospital with Nanjing Medical University	Nanjing	Jiangsu
China	the Affiliated Hospital of Nantong University	Nantong	Jiangsu

Sponsors (3)

Lead Sponsor	Collaborator
Nantong University	The First Affiliated Hospital with Nanjing Medical University, University of Melbourne

Country where clinical trial is conducted

China, 

References & Publications (13)

Brown JC, Schmitz KH. The prescription or proscription of exercise in colorectal cancer care. Med Sci Sports Exerc. 2014 Dec;46(12):2202-9. doi: 10.1249/MSS.0000000000000355. — View Citation

Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. Cancer Cell. 2018 Apr 9;33(4):570-580. doi: 10.1016/j.ccell.2018.03.015. Review. — View Citation

Hamasaki H. Exercise and gut microbiota: clinical implications for the feasibility of Tai Chi. J Integr Med. 2017 Jul;15(4):270-281. doi: 10.1016/S2095-4964(17)60342-X. Review. — View Citation

Hong QY, Wu GM, Qian GS, Hu CP, Zhou JY, Chen LA, Li WM, Li SY, Wang K, Wang Q, Zhang XJ, Li J, Gong X, Bai CX; Lung Cancer Group of Chinese Thoracic Society; Chinese Alliance Against Lung Cancer. Prevention and management of lung cancer in China. Cancer. 2015 Sep 1;121 Suppl 17:3080-8. doi: 10.1002/cncr.29584. Review. — View Citation

Hung R, Krebs P, Coups EJ, Feinstein MB, Park BJ, Burkhalter J, Ostroff JS. Fatigue and functional impairment in early-stage non-small cell lung cancer survivors. J Pain Symptom Manage. 2011 Feb;41(2):426-35. doi: 10.1016/j.jpainsymman.2010.05.017. Epub 2011 Jan 8. — View Citation

John LD. Self-care strategies used by patients with lung cancer to promote quality of life. Oncol Nurs Forum. 2010 May;37(3):339-47. doi: 10.1188/10.ONF.339-347. — View Citation

Jones LW, Watson D, Herndon JE 2nd, Eves ND, Haithcock BE, Loewen G, Kohman L. Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer. Cancer. 2010 Oct 15;116(20):4825-32. doi: 10.1002/cncr.25396. — View Citation

Keohane DM, Woods T, O'Connor P, Underwood S, Cronin O, Whiston R, O'Sullivan O, Cotter P, Shanahan F, Molloy MGM. Four men in a boat: Ultra-endurance exercise alters the gut microbiome. J Sci Med Sport. 2019 Sep;22(9):1059-1064. doi: 10.1016/j.jsams.2019.04.004. Epub 2019 Apr 18. — View Citation

Lin YY, Rau KM, Lin CC. Longitudinal study on the impact of physical activity on the symptoms of lung cancer survivors. Support Care Cancer. 2015 Dec;23(12):3545-53. doi: 10.1007/s00520-015-2724-7. Epub 2015 Apr 9. — View Citation

Polanski J, Jankowska-Polanska B, Rosinczuk J, Chabowski M, Szymanska-Chabowska A. Quality of life of patients with lung cancer. Onco Targets Ther. 2016 Feb 29;9:1023-8. doi: 10.2147/OTT.S100685. eCollection 2016. Review. — View Citation

Schmitz KH, Holtzman J, Courneya KS, Mâsse LC, Duval S, Kane R. Controlled physical activity trials in cancer survivors: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2005 Jul;14(7):1588-95. Review. — View Citation

Wang JW, Gong XH, Ding N, Chen XF, Sun L, Tang Z, Yu DH, Yuan ZP, Wang XD, Yu JM. The influence of comorbid chronic diseases and physical activity on quality of life in lung cancer survivors. Support Care Cancer. 2015 May;23(5):1383-9. doi: 10.1007/s00520-014-2494-7. Epub 2014 Oct 31. — View Citation

Zhang LL, Wang SZ, Chen HL, Yuan AZ. Tai Chi Exercise for Cancer-Related Fatigue in Patients With Lung Cancer Undergoing Chemotherapy: A Randomized Controlled Trial. J Pain Symptom Manage. 2016 Mar;51(3):504-11. doi: 10.1016/j.jpainsymman.2015.11.020. Epub 2015 Dec 22. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adherence to the program	Intervention group participants who complete either 17 out of 24 hospital-sessions or 12 out of 24 hospital sessions and at least 10 minutes walking at home twice a week will be considered to be adherent to the protocol.	12 weeks post-program
Other	Program costs	We will consider the additional implementation costs of rehabilitation, including patient costs, compared with usual care in addition to the downstream cost differences associated with hospital usage (including hospital admissions and their length of stay, visits to accident and emergency and clinic appointments). Health from baseline to 6 months (with modelling to 12 months) will be measured using Quality Adjusted Life Years (QALYs) and then within trial follow-up cost per additional QALY will be estimated and compared with levels considered to provide good value for money. Probabilistic sensitivity analysis will be conducted to explore the robustness of the conclusions reached.	Baseline, 12 weeks (post-program) and 6 months
Other	Survival	We will follow up survival in all groups and censor at 1 year.	12 months post baseline
Primary	European Organization for the Research and Treatment of Cancer questionnaire (EORTC QLQ-C30-LC13)	HRQoL will be assessed with the European Organization for the Research and Treatment of Cancer questionnaire (EORTC QLQ-C30-LC13) at baseline, 12 weeks and 6 months post-baseline. Score ranges from 0~100.For functional domains and global health status/quality of life scale, higher score means better status. While for symptom domains and single-items, lower scores represent less symptoms.	The primary time point is the change from baseline to 12 weeks. This outcome will also be measured at 6 months post-baseline.
Secondary	Functional Exercise Capacity	All participants will complete a Incremental Shuttle Walking Test following published guidelines.	1) baseline, 2) 12 week, and 3) 6 months post-baseline.
Secondary	Seven-day Physical Activity	Will be measured objectively using an pedometer at baseline, 12 weeks and 6 months post-baseline. It is worn for 7 consecutive days and a minimum of four full days (8 hours/day) is required for valid analyses.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	Grip strength	A hand held dynamometry manual muscle test is a common, simple measurement of strength and has been used in many patient populations including cancer and is reliable and sensitive to change. We will measure hand grip strength bilaterally	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	30-Second Chair Stand	To test leg strength and endurance. A below average score indicates a risk for falls.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	International physical activity questionnaire(IPAQ)	The International Physical Activity Questionnaire (IPAQ) scores are categorised as high/moderate (meeting PA guidelines) or low (not meeting PA guidelines) and as a continuous energy expenditure score (metabolic equivalent of task (MET) minutes per week). Higher scores indicate increased PA.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	Self-Rating Anxiety Scale(SAS)	To test the anxiety level of the patients. It has 20 items and are four-point scale(rated 1-4), some of the items are reversely scored. Score ranges from 0~100, higher score means worse anxiety status.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	Self-Rating Depression Scale(SDS)	To test the depression level of the patients. It has 20 items and are four-point scale(rated 1-4), some of the items are reversely scored. Score ranges from 0~100, higher score means worse depression status.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	Pittsburgh Sleep Quality Index(PSQI)	Pittsburgh Sleep Quality Index(PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores. The sum of scores for these seven components yields one global score, and the higher score means the worse sleep quality. Score ranges from 0~21, higher score means worse sleep quality.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	MD Anderson Symptom Inventory-lung cancer (MDASI-LC)	To evaluate to the severity and interference of the symptom in participants.The MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) will be used to measure symptom severity and distress. The symptom severity component comprises 13 core and three lung cancer specific items, measured on a 0-10 numerical rating scale. The average score is reported, with higher scores indicating worse symptoms. The MCID in lung cancer has been reported as being between 0.98 to 1.21 points	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	Australia-modified Karnofsky Performance Status(AKPS)	To evaluate the performance of the whole well-being of the participants. Score ranges from 0~100, higher score means better status.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.
Secondary	European quality of life 5-dimension 5-level(EQ-5D-5L)	European quality of life 5-dimension 5-level(EQ-5D-5L) is a family of instruments to describe and value health. It comprises a short descriptive system questionnaire and a visual analogue scale that are cognitively undemanding. A value set provides values(weights) for each health state description according to the preferences of the general population of a country/region.	1) baseline, 2) 12 weeks, and 3) 6 months post-baseline.