Plain English Summary
Background and study aims
Immunotherapy is a cancer treatment that uses the body's immune system to fight cancer in advanced stages. Despite the success of immunotherapy, there are still several barriers to extending its clinical benefit to a greater number of patients. Although there are patients who respond well to immunotherapy, some patients do not respond to the same treatment. At present, it is not well understood how and why this occurs. The ability to predict the response to immunotherapy should allow the development of personalized treatments, improve survival rates and reduce unnecessary exposure of patients to toxic medications. To achieve this, this study will evaluate a wide range of small molecules (metabolites) in blood and urine using different techniques and try to identify which metabolites are useful for predicting the response to treatment.
Who can participate?
Patients aged over 18 with stage III and IV non-small cell lung cancer, who are candidates for immunotherapy treatment
What does the study involve?
This study involves first-line treatments with immunotherapy exclusively or immunotherapy combined with chemotherapy, and second-line immunotherapy treatments after a chemotherapy-based first-line treatment. Fasting morning blood and urine samples will be collected and metabolites will be measured before and after immunotherapy.
What are the possible benefits and risks of participating?
Potential benefits of participating are a good response to immunotherapy and improvement of survival rates. The possible risks of participating include treatment toxicities or deterioration of performance status and disease progression.
Where is the study run from?
University Hospital Sant Joan de Reus (Spain)
When is the study starting and how long is it expected to run for?
September 2020 to December 2023
Who is funding the study?
Instituto de Salud Carlos III (Spain)
Who is the main contact?
Dr Christopher Papandreou
papchris10@gmail.com
Trial website
Contact information
Type
Scientific
Primary contact
Dr Christopher Papandreou
ORCID ID
http://orcid.org/0000-0002-6803-507X
Contact details
St/Sant Llorenç 21
Reus
N/A
Spain
+34 (0)638910914
papchris10@gmail.com
Type
Scientific
Additional contact
Dr Josep Gumà Padró
ORCID ID
Contact details
Avinguda Josep Laporte
2.
Reus
43204
Spain
+34 (0)629392561
jguma@grupsagessa.com
Additional identifiers
EudraCT number
Nil known
ClinicalTrials.gov number
Nil known
Protocol/serial number
Nil known
Study information
Scientific title
Metabolomic profiles in blood and urine as predictors of response to immunotherapy in lung cancer patients
Acronym
MetLung
Study hypothesis
The hypothesis of this proposal is that specific metabolites in blood and urine predict the response to immunotherapy. The researchers also hypothesize that immunotherapy will modulate specific metabolites in blood and urine differently in responders than in non-responders.
Ethics approval
Approved 09/04/2020, Institut d'Investigació Sanitària Pere Virgili (IISPV) - Ethical Committee (Hospital Universitaria Sant Joan. Avda. Josep Laporte, 2. Planta 0 - E2 43204 Reus, Hospital Universitari de Tarragona Joan XXII. c/ Doctor Mallafrè, 4 Parc Sanitari Hosp.Joan XXIII, 43005 Tarragona; +34 (0)977 759 395; ceim@iispv.cat), ref: CEIm: 072/2020
Study design
Prospective observational single-centre study
Primary study design
Observational
Secondary study design
Longitudinal study
Trial setting
Hospitals
Trial type
Other
Patient information sheet
Not available in web format, please use the contact details to request a participant information sheet
Condition
Locally advanced or metastatic non-small cell lung cancer
Intervention
First-line treatments with immunotherapy exclusively (those whose tumours express more than 50% of PDL1) or immunotherapy combined with chemotherapy (expression of PDL1 between 1 and 49%), and second-line immunotherapy treatments after a chemotherapy-based first line.
For the metabolomic analysis in blood and urine samples, different analytic platforms will be used according to the sample. Three different metabolomics platforms will be used: proton nuclear magnetic resonance (1H NMR), liquid chromatography coupled to mass spectrometry (LC-MS) and gas chromatography coupled to mass spectrometry (GC-MS). Targeted and untargeted metabolomics will also be performed in blood and urine samples. The duration of follow-up will be 12 weeks.
Intervention type
Other
Phase
Drug names
Primary outcome measure
Metabolites in blood and urine will be measured using targeted and untargeted approaches, and 1H NMR, LC-MS and GC-MS analytical techniques at baseline and 12 weeks
Added 12/08/2020:
The first evaluation of the response to immunotherapy will be carried out at 9-12 weeks of treatment with computed tomography scan and following the guidelines for the Immune Response Evaluation Criteria in Solid Tumours (iRECIST) and then every 3 months or at the time when there is suspicion of progression, and classified according to disease control (complete response, partial response, and stable disease) and progressive response (non-response).
Secondary outcome measures
1. Toxicity assessment reflected in the medical history, classifying it by affected organ and by degree of severity (1-4) based on ESMO clinical practice guidelines, performed at 12 weeks
2. Fecal gut microbiome measured using V2-V4 r16S RNA and/or next generation sequencing platform (NGS)
3. Fecal metabolome measured using NMR/LC-MS/GC-MS
4. Epigenetic tags (i.e. miRNAs, long ncRNA, telomeres, DNA methylation) measured using qPCR arrays for miRNAs and lncRNA, Luminex-based assay for telomere length, pyrosequencing for DNA methylation
5. Inflammation and oxidation parameters measured using commercial ELISA methods and/or multiplexing
6. Dietary intake measured using a validated food-frequency questionnaire
7. Antibiotic use measured using self-report
8. Probiotic exposure measured using self-report
Measured at baseline and 12 weeks
Overall trial start date
01/09/2020
Overall trial end date
31/12/2023
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Patients older than 18 years with stage III and IV NSCLC candidates for immunotherapy treatment
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
180
Participant exclusion criteria
1. Patients with another primary malignancy diagnosed in the previous 5 years (except for cervical carcinoma in situ and non-melanoma skin cancer)
2. Patients with tumours expressing actionable mutations in EGFR, ALK or ROS1
3. Patients with stage IV severe kidney disease (creatinine clearance < 30 ml/min)
4. Patients with severe liver disease (hepatitis, cirrhosis)
5. Patients with low Performance Status (ECOG 3-4)
6. Patients who refuse to sign the informed consent
7. Any previous systemic immunotherapeutic treatment will also make the patient ineligible for the study
Recruitment start date
01/09/2020
Recruitment end date
31/08/2022
Locations
Countries of recruitment
Spain
Trial participating centre
Hospital Universitari Sant Joan
Av/del Dr. Josep Laporte, 2
Reus
43204
Spain
Trial participating centre
Institute of Health Pere Virgili
Av/del Dr. Josep Laporte, 2
Reus
43204
Spain
Trial participating centre
Universitat Rovira i Virgili
Carrer de l'Escorxador, s/n
Tarragona
43003
Spain
Sponsor information
Organisation
Instituto de Salud Carlos III
Sponsor details
St/Sinesio Delgado
4
Madrid
28029
Spain
+34 (0)91 822 20 00
oficina.informacion@isciii.es
Sponsor type
Government
Website
Funders
Funder type
Government
Funder name
Instituto de Salud Carlos III
Alternative name(s)
Institute of Health Carlos III, Carlos III Health Institute, ISCIII
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Spain
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer-reviewed journal.
IPD sharing statement
The datasets generated during and/or analysed during the current study are/will be available upon request from Dr Christopher Papandreou (papchris10@gmail.com).
Intention to publish date
06/08/2024
Participant level data
Available on request
Basic results (scientific)
Publication list