Clinical trial NCT03960034: Cachexia in NSCLC Patients: Diagnosis, Characterization, Prognosis, Functional and Skeletal Muscle Implications
Official title: Cachexia in Advanced NSCLC Patients: Diagnosis, Characterization, Prognosis, Functional Implications and Validation of Skeletal Muscle Disfunction Markers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: NSCLC Stage IV
Keywords: Cachexia
Skeletal Muscle Atrophy
Physical Functional Performance
Prognosis
Lead sponsor: Instituto do Cancer do Estado de São Paulo
Sponsor class: OTHER
First posted: 2019-05-22
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: NSCLC patient, current smokers or ex-smokers treatment naive with good Eastern Cooperative Oncology Group Performance status (ECOG-PS). A smoker population with no known cancer will be used as controls (n=10)

Brief summary: LUCAX01 is a cohort study with patients with advanced NSCLC in tobacco users. in this study, patients will be submitted to baseline physical tests, blood and biopsy sample collection, and the main objective is to study the functional and prognostic implications of cachexia and to validate skeletal muscle dysfunction markers.

Detailed description: Non-small-cell lung cancer (NSCLC) is currently the neoplasm leading in deaths worldwide and in Brazil, it figures as the second most common cancer in terms of the number of deaths. Patients are usually diagnosed in advanced stages and, consequently, more than 45% of all patients are diagnosed with cachexia. This syndrome is characterized by a loss of muscle mass with or without fat loss and it cannot be reversed by nutritional support. In the physiopathology of cachexia, generally are present exacerbated inflammation, severe loss of muscle contractile proteins, leading to fatigue and increased mortality. Furthermore, patients with cachexia usually do present lower response rates to anticancer treatments and it is also associated with a worse overall prognosis.

Treatments directed to mitigate muscle loss in these patients are awaited. Cohort studies do suggest a significant positive impact of physical fitness and prognosis in different chronic diseases; however, its impact in advanced NSCLC patients is not clear. Here our aim is to better understand the relationship between cachexia and physical fitness variables (muscle and cardiorespiratory function, body composition, and daily physical activity level) with prognosis and mortality in a group of NSCLC patients, as well as to study the effect of chemotherapy on these variables. Besides that, will be evaluated the skeletal muscle, Treg lymphocytes, and inflammatory biomarkers and compare cachectic and non-cachectic patients.

Sixty NSCLC patients will be accrued. Will be assessed the maximum oxygen consumption, daily physical activity, muscle function, muscle morphology, anxiety, depression, performance status, and fatigue pre-treatment. Blood and muscle biopsy samples will be collected. The prognostic impact of these physical fitness variables will be defined, as well as their predictive value in terms of response to anticancer treatments in advanced NSCLC patients.

Eligibility criteria: Inclusion Criteria:

* Advanced stage IVa or IVb NSCLC patients histologically diagnosis.
* Eastern Cooperative Oncology Group Performance status 0 - 2
* Treatment-naive
* Current smokers or ex-smokers
* Normal renal, hepatic and hematological functions
* Able to perform the physical functional tests
* Able to read and sign the consent form

Exclusion Criteria:

* Initiate treatment before initiate
* Diagnostic of tumor mutation ( epidermal growth factor receptor, Anaplastic lymphoma kinase)

Obs: A smoker population with no known cancer will be used as controls (n=10)

Primary outcomes:
measure: Overall survival in cachectic and non-cachectic patient
timeFrame: 2 year
Secondary outcomes:
measure: Physical fitness and response to treatment
timeFrame: 1 year
measure: Physical fitness and toxicity
timeFrame: 1 year
measure: Cancer cachexia skeletal muscle pathways
timeFrame: 1 year
measure: Cluster of Differentiation 4+ (CD4+) population in cachectic and non-cachectic patient.
timeFrame: 1 year
measure: Cluster of Differentiation 25+ (CD25+) population.
timeFrame: 1 year
measure: Forkhead box P3 regulatory T (Fox-p3+) population.
timeFrame: 1 year
Other outcomes:
Locations:
city: São Paulo
country: Brazil
facility: Instituto do Câncer do Estado de São Paulo
state: SP
Study officials:
affiliation: Instituto do Câncer do Estado de São Paulo - FMUSP
name: Gilberto de Castro Junior, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: