Condition category
Cancer
Date applied
15/07/2020
Date assigned
17/07/2020
Last edited
12/08/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

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

http://www.isciii.es/

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

Publication citations

Additional files

Editorial Notes

12/08/2020: Primary outcome measure updated. 03/08/2020: The sponsor and funder were changed from Institut d'Investigació Sanitària Pere Virgili to Instituto de Salud Carlos III. 16/07/2020: Trial's existence confirmed by Institut d'Investigació Sanitària Pere Virgili.