POSITIVE - Study (Part III) Heidelberg

Advanced NSCLC Clinical Trial

— POSITIVE  

Official title:

Physical Exercise Program in Lung Cancer Patients With Non-operable Disease Undergoing Palliative Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02055508
• Other study ID #: POSITIVE-III-S-326/2013
• Status: Completed
• Phase: N/A
• Start date: December 2013
• Est. completion date: March 2018

Study information

• Verified date: August 2018
• Source: German Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators plan to evaluate, in a randomized, controlled phase III trial in patients with advanced non-small cell lung cancer (NSCLC), the effects of a 24-week exercise intervention program (EIP) on quality of life, physical functioning and immune function parameters. Eligible patients (n=250) will be enrolled in the Clinic for Thoracic Diseases, Heidelberg, over a time period of two years and followed up for a total of 12 months.

Patients will be randomized either to EIP plus Care Management Phone Calls (CMPC) versus CMPC alone (besides a proper symptom and side effect management CMPC ensures the potential influence of social contacts that can be anticipated for the patients in the intervention group).

Our primary aims are to investigate whether a combination of a partly supervised (in- and outpatient) and partly home-based endurance and resistance training improves quality of life (QoL) and lowers levels of fatigue (evaluation via the standardized and validated questionnaires FACT-L and MFI). In addition we propose to evaluate the effects of EIP on tumor specific immune responses. Biomarkers of immune function will be measured by cellular immunity and cytokine and chemokine panels.

Further secondary outcomes include measurement of anxiety, depression and demoralization, physical performance parameters (e.g. improvement in walk distance, muscle strength), as well as overall and progression free survival analyses.

The study builds on a previous feasibility study of a 8 weeks exercise intervention trial in patients with advanced NSCLC with the results being utilized in the design of the here proposed trial.

The investigators hypothesize that patients randomized in the exercise intervention group will show improved QoL and reduced fatigue, as well as improved physical functioning and increased tumor specific immune responses.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: March 2018
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• NSCLC stage IIIB/IV

• receiving systemic treatment (palliative radiotherapy accepted)

• BMI > 18

• ECOG (Eastern Cooperative Oncology Group) performance status = 2

• signed informed consent

Exclusion Criteria:

• serious active infection (i.e. requiring an iv antibiotic, antifungal or antiviral agent)

• inability to walk

• immobility (more than two days)

• previously untreated (non-irradiated or non-resected) symptomatic brain metastases;permitted are: (1) previously treated brain metastases [radiotherapy, surgery, dexamethasone dosage 8 mg per day, anti-epileptic therapy]; (2) asymptomatic brain metastases without additional therapy requirement

• severe neurologic impairment (e.g. apoplectic insult, Morbus Parkinson, pareses of extremities)

• severe cardiac impairment (e.g. cardiac insufficiency NYHA (New York Heart Association) > III, myocardial infarction within the last three months, unexplained syncopal events, severe cardiac arrhythmias, high grade aortic stenosis)

• severe respiratory insufficiency

• uncontrolled pain

• abuse of alcohol or drugs reducing compliance to the study

• bone metastasis inducing skeletal fragility

• any circumstance that would impede ability to give informed consent or adherence to study requirements.

Related Conditions & MeSH terms

• Advanced NSCLC
• First Line Treatment

Intervention

Behavioral:
• Exercise Intervention

Other:
• Care-Management-Phone-Calls

Locations

Country	Name	City	State
Germany	Thoracic Oncology Clinic for Thoracic Diseases	Heidelberg	Baden-Württemberg

Sponsors (3)

Lead Sponsor	Collaborator
German Cancer Research Center	National Center for Tumor Diseases, Heidelberg, University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Events	Safety analyses will be based on Adverse Events (AE´s), Severe Adverse Events (SAE´s), and Suspected Unexpected Serious Adverse Reaction (SUSARs) recorded during the study. Of particular interest are AEs, SAEs and SUSARs deemed to be potentially causally related to the endurance and resistance training.	baseline until 6 month after enrolement
Other	Translational Program / Immunology	Quantification (Q) of immune cells: Multicolor flow cytometry from cryopreserved Peripheral Blood Mononuclear Cell (PBMC), CD (cluster of differentiation) 4+ and CD 8+ T cells, effector, naïve and activated T cells, regulatory T cells (Treg) and their functional subsets, natural killer cells, B cells, monocytes and monocyte-derived myeloid suppressor cells will be assessed.; Q. of tumor antigen reactive effector/memory T cells: Will be done by interferon gamma Enzyme Linked Immuno Spot Assays from PBMC using a panel of defined tumor antigens presented by generated autologous dendritic cells as antigen presenting cells and purified T cells as responder cells.; Detection of tumor reactive Treg: Will be done by established Treg specificity assay based on the increased suppressive activity of specifically activated regulatory T cells.; Q. of key immune effector molecules: Will be done for app. 14 different cytokines and chemokines from cryopreserved serum samples.	baseline, 3 & 6 month after enrolement
Primary	QoL: Physical Well-Being (FACT-L)	The FACT-L (Functional Assessment of Cancer Therapy-Lung) questionnaire comprises of 36 items and deter-mines the quality of life in patients with lung cancer. It is separated in the subcategories "physical well-being" (PRIMARY OUTCOME), "emotional well-being", "social well-being", "functional well-being and disease-specific items". It is widely used in clinical studies and was already applied in exercise intervention studies in lung cancer patients	assessed after 12 weeks of enrolement
Primary	General Fatigue (MFI)	The MFI (Multidimensional Fatigue Inventory) questionnaire (20 items) evaluates the extent of chronic fatigue and is divided into the 5 subscales "general fatigue", "physical fatigue", "mental fatigue", "reduced motivation" and "reduced activity". The MFI questionnaire is widely used in oncological studies and an adequate number of comparative samples exists.	assessed after 12 weeks of enrolement
Secondary	Physical Performance (endurance and strength capacity)	6-Minute Walk Test (endurance capacity) The 6 minute walk test is feasible and safe to determine patients physical capacity. Patients are instructed to walk in 6 min. as many meters as possible with oxygen saturation and pulse rate being measured concomitantly.; Hand-held Dynamometry (isometric strength capacity) The hand-held dynamometry is a standardized instrument to measure muscular strength. In the study 6 major muscle groups of upper and lower extremities will be assessed for their isometric power.	assessed every 3 month after enrolement until month 12
Secondary	Psychosocial Parameters (e.g. depression, anxiety, demoralization)	PHQ(Ultra-Brief Patient Health Questionnaire)-4 : The PHQ-4 (Ultra-Brief Patient Health Questionnaire) questionnaire is a short instrument comprising of 4 items to detect the extent of depression and anxiety. It provides sufficient diagnostic accuracy for major depression and can be used as a screening instrument in cancer populations.; DS (Demoralization Scale) The demoralization scale (DS) is a relatively new developed questionnaire to detect the extent of existential distress in cancer patients. The German version was validated in 2011 and comprises of 24 questions. The results of the validation showed that the concept of demoralization is a useful instrument to describe the different states of existential distress and the individual incapacity to cope effectively with stressful situations.	assessed every 3 month after enrolement until month 12
Secondary	Overall survival		for the period of 1 year after enrolement
Secondary	progression-free survival		for the period of 1 year after enrolement