Clinical trial NCT03156868: Analysis of Soluble Mediators,Cytokines and FACs as Prognostic Factors in Advanced Non-squamous Lung Carcinoma
Official title: Analysis of Soluble Mediators, Cytokines, and Circulating Angiogenic Factors (FACs) as Potential Predictors / Prognostic Factors in Antiangiogenic Therapy Following Failure of First-line Chemotherapy in Advanced Non-squamous Lung Carcinoma
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Spanish Lung Cancer Group
Sponsor class: OTHER
First posted: 2017-05-17
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with advanced non-squamous lung carcinoma without molecular alterations susceptible to be treated with specific inhibitors (EGFR mutation, ALK translocation, ROS1 fusion) that have progressed to the first line of chemotherapy and are subsidiary to a second treatment line.

Brief summary: Recent studies have shown that the assessment of a set of cytokines and / or circulating angiogenic factors (FACs) could be used to identify prognostic factors predictive of efficacy and / or potential mechanisms of resistance to antiangiogenic agents

Detailed description: Current management of patients with locally advanced or metastatic NSCLC, with no susceptible molecular alterations (EGFR mutation, ALK translocation, ROS1 fusion), includes combinations based on platinum in the first line of treatment, while in the second Line, there are three possibilities in monotherapy: docetaxel, erlotinib and pemetrexed. Pemetrexed is exclusively indicated for patients with a NSCLC of non-squamous histology. Although all of them have been shown to increase progression-free survival (PFS) and overall survival (OS), the median time to progression is maintained at 3 months, and the median overall survival at 8-9 months.

Recently, other therapeutic options have been incorporated in the context of the second line. Firstly, two antiangiogenic drugs: nintedanib and ramucirumab. The combination of nintedanib or ramucirumab with docetaxel in the second line of treatment has been shown to provide a significant increase in SLP and SG compared to docetaxel (9,11). One of the criticisms of the results of these two trials, common to all antiangiogenic treatments, is the lack of predictive factors that help us to better select the patients who would benefit from such treatment, as well as a better rationalization of Economic costs. On the other hand, recent data from new strategies based on immunotherapies in lung cancer indicate that nivolumab, a PD-1 antibody (Programmed cell death-1), has shown benefit in terms of survival versus docetaxel monotherapy both in Histology as squamous adenocarcinoma after failure to a platinum-based prior line.

Based on the above, the objective of this project is to analyze a panel of soluble mediators by means of multiparametric immunoassay techniques in samples of peripheral blood (at baseline, during treatment, and progression of the disease) obtained from patients With advanced lung adenocarcinoma, without molecular alterations treatable with anti-target drugs, that have progressed to a first line of chemotherapy, irrespective of whether they have received treatment with immunotherapies, and that they will be treated in the second line with chemotherapy (docetaxel) In combination or not with an antiangiogenic. It is a question of analyzing markers or panels of them with a prognostic / predictive meaning, as well as those that could be related to mechanisms of resistance to the administered treatments.

Eligibility criteria: Inclusion Criteria:

1. Patients aged ≥ 18 years
2. Histological and / or cytological confirmation of non-squamous pulmonary carcinoma, stage IIIB / IV or recurrent
3. Failure to a first line of chemotherapy for advanced or recurrent disease. Patients who have received 2 treatment lines will also be included and this will be the 3 rd line provided that during one of the previous lines they have received immunotherapy or antidandial therapies (in patients with a wild type or unknown mutational status).
4. ECOG 0 or 1
5. Life expectancy greater than 12 weeks.
6. Written informed consent of the patient in accordance with current regulations

Exclusion Criteria:

1. Receive more than one line of chemotherapy treatment for advanced disease
2. Hepatic function (one or more of the following values would exclude the patient): a. Total bilirubin outside the limits of normality; B. For patients without hepatic metastasis: ALT or AST\> 1.5 times ULN; C. For patients with hepatic metastases: total bilirubin outside the limits of normality, ALT or AST\> 2.5 times the ULN.
3. Hemogram (one or more of the following values would exclude the patient): a. Absolute neutrophil count \<1,500 / mm3; B. Platelets \<100,000 / mm 3; C. Hemoglobin \<9.0 g / dl.
4. Situations such as the following: a. Active serious infections, especially if they require antimicrobial or systemic antibiotic treatment, or active or chronic infection with hepatitis C or B virus; B. Severe disease or non-oncological concomitant disease such as neurological, psychiatric or infectious disease or active ulcers (digestive tract, skin) or relevant analytical abnormality; C. Patients who are sexually active and do not want to use a medically acceptable method of contraception during the study and for at least 3 months after the completion of active treatment; D. Psychological, family, sociological or geographical factors; and. Alcoholism or current drug addiction; F. Preexisting ascites and / or clinically significant pleural effusion; G. Decompensated diabetes mellitus or other contraindication to treatment with corticosteroids at high doses
5. Pregnancy or breastfeeding; The women must have obtained a negative result in a pregnancy test before starting the treatment

Primary outcomes:
measure: Soluble mediators in relation to progression free survival
timeFrame: At time of progression, an average of 1 year
Secondary outcomes:
measure: Soluble mediators in relation to response rate
timeFrame: at time of first response, an average of 3 months
Other outcomes:
Locations:
city: Elche
country: Spain
facility: Hospital de Elche
state: Alicante
city: Torrevieja
country: Spain
facility: Hospital de Torrevieja
state: Alicante
city: Badalona
country: Spain
facility: ICO-Badalona
state: Barcelona
city: Sant Cugat Del Vallès
country: Spain
facility: Hospital General de Catalunya
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Sanitari de Terrassa
state: Barcelona
city: Las Palmas de Gran Canaria
country: Spain
facility: Complejo Hospitalario Universitario Insular de Gran Canaria
state: Gran Canaria
city: Leganés
country: Spain
facility: Hospital Severo Ochoa
state: Madrid
city: Palma De Mallorca
country: Spain
facility: Hospital Son Llàtzer
state: Mallorca
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Alzira
country: Spain
facility: Hospital Universitario de la Ribera
state: Valencia
city: Alicante
country: Spain
facility: H.G.U. Alicante
city: Barcelona
country: Spain
facility: Hospital Universitari Quirón Dexeus
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Castelló
country: Spain
facility: H. Provincial de Castellón
city: Jaén
country: Spain
facility: Hospital de Jaén
city: Lugo
country: Spain
facility: Hospital Lucus Agustí
city: Madrid
country: Spain
facility: H.U. Puerta de Hierro
city: Madrid
country: Spain
facility: H. Clínico San Carlos
city: Salamanca
country: Spain
facility: Hospital Clinico de Salamanca
city: Santa Cruz de Tenerife
country: Spain
facility: Hospital Nuestra Señora Candelaria
city: Tarragona
country: Spain
facility: Hospital Sant Pau i Santa Tecla
city: Valencia
country: Spain
facility: H. General U. de Valencia
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Valencia
country: Spain
facility: Hospital de Sagunto
Study officials:
affiliation: Hospital General Universitario de Valencia
name: Carlos Camps, MD
role: PRINCIPAL_INVESTIGATOR
References: