Cachexia in NSCLC Patients: Diagnosis, Characterization, Prognosis, Functional and Skeletal Muscle Implications (LUCAX01)

Cachexia in Advanced NSCLC Patients: Diagnosis, Characterization, Prognosis, Functional Implications and Validation of Skeletal Muscle Disfunction Markers

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.

Study Overview

• Status: Completed
• Conditions: NSCLC Stage IV

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.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• 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)

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival in cachectic and non-cachectic patient	Survival will be measured to understand the prognostic impact of cancer cachexia in NSCLC patients.	2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical fitness and response to treatment	Response Evaluation in solid tumors (RECIST 1.1) will be used to evaluate the relationship between physical fitness and response to chemotherapy.	1 year
Physical fitness and toxicity	Common terminology criteria for adverse events (CTCAE 5.0) will be used to evaluate the relationship between physical fitness and toxicities related to chemotherapy.	1 year
Cancer cachexia skeletal muscle pathways	Determination of down and up-regulated skeletal muscle pathways cachectic and non-cachectic patient using RNA-sec.	1 year
Cluster of Differentiation 4+ (CD4+) population in cachectic and non-cachectic patient.	Determination of CD4+ profile in cachectic and non-cachectic patients using flow cytometry.	1 year
Cluster of Differentiation 25+ (CD25+) population.	Determination of CD25+ profile in cachectic and non-cachectic patients using flow cytometry.	1 year
Forkhead box P3 regulatory T (Fox-p3+) population.	Determination of Fox-p3+ profile in cachectic and non-cachectic patients using flow cytometry.	1 year

Collaborators and Investigators

• Sponsor: Instituto do Cancer do Estado de São Paulo
• Investigators: Principal Investigator: Gilberto de Castro Junior, MD, PhD, Instituto do Câncer do Estado de São Paulo - FMUSP

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 10, 2017
• Primary Completion (ACTUAL): December 30, 2020
• Study Completion (ACTUAL): December 30, 2020

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: May 21, 2019
• First Posted (ACTUAL): May 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): April 15, 2022
• Last Update Submitted That Met QC Criteria: April 13, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Prognosis; Cachexia; Physical Functional Performance; Skeletal Muscle Atrophy
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Body Weight; Body Weight Changes; Emaciation; Weight Loss; Wasting Syndrome; Cachexia
• Other Study ID Numbers: NP802/15

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No