Measuring small molecules (metabolites) in blood and urine that predict the response to immunotherapy in lung cancer patients

ISRCTN ISRCTN98848959
DOI https://doi.org/10.1186/ISRCTN98848959
Submission date
15/07/2020
Registration date
17/07/2020
Last edited
29/01/2025
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

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 2022

Who is funding the study?
Instituto de Salud Carlos III (Spain)

Who is the main contact?
Dr Christopher Papandreou
papchris10@gmail.com

Contact information

Dr Christopher Papandreou
Scientific

St/Sant Llorenç 21
Reus
-
Spain

ORCiD logoORCID ID 0000-0002-6803-507X
Phone +34 (0)638910914
Email papchris10@gmail.com
Dr Josep Gumà Padró
Scientific

Avinguda Josep Laporte, 2.
Reus
43204
Spain

Phone +34 (0)629392561
Email josep.guma@salutsantjoan.cat

Study information

Study designProspective observational single-centre study
Primary study designObservational
Secondary study designLongitudinal study
Study setting(s)Hospital
Study typeOther
Participant information sheet Not available in web format, please use the contact details to request a participant information sheet
Scientific titleMetabolomic profiles in blood and urine as predictors of response to immunotherapy in lung cancer patients
Study acronymMetLung
Study objectivesThe 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(s)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
Health condition(s) or problem(s) studiedLocally advanced or metastatic non-small cell lung cancer
InterventionFirst-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 typeOther
Primary outcome measureMetabolites 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 measures1. 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 study start date01/09/2020
Completion date31/12/2022

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants180
Total final enrolment131
Key inclusion criteriaPatients older than 18 years with stage III and IV NSCLC candidates for immunotherapy treatment
Key exclusion criteria1. 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
Date of first enrolment01/09/2020
Date of final enrolment31/12/2022

Locations

Countries of recruitment

  • Spain

Study participating centres

Hospital Universitari Sant Joan
Av/del Dr. Josep Laporte, 2
Reus
43204
Spain
Institute of Health Pere Virgili
Av/del Dr. Josep Laporte, 2
Reus
43204
Spain
Universitat Rovira i Virgili
Carrer de l'Escorxador, s/n
Tarragona
43003
Spain

Sponsor information

Instituto de Salud Carlos III
Government

St/Sinesio Delgado
4
Madrid
28029
Spain

Phone +34 (0)91 822 20 00
Email oficina.informacion@isciii.es
Website http://www.isciii.es/
ROR logo "ROR" https://ror.org/00ca2c886

Funders

Funder type

Government

Instituto de Salud Carlos III
Government organisation / National government
Alternative name(s)
SaludISCIII, InstitutodeSaludCarlosIII, Instituto de Salud Carlos III | Madrid, Spain, Carlos III Institute of Health, Institute of Health Carlos III, Carlos III Health Institute, ISCIII
Location
Spain

Results and Publications

Intention to publish date01/12/2025
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planPlanned publication in a high-impact peer-reviewed journal.
IPD sharing planThe datasets generated during and/or analysed during the current study are/will be available upon request from Dr Christopher Papandreou (papchris10@gmail.com).

Editorial Notes

29/01/2025: The following changes were made:
1. The overall study end date was changed from 31/12/2023 to 31/12/2022.
2. The intention to publish date was changed from 06/08/2024 to 01/12/2025.
03/01/2023: The contact confirmed the record is up to date.
03/01/2023: The final enrolment number has been added.
18/11/2021: A contact email was changed.
08/11/2021: The recruitment end date was changed from 31/08/2022 to 31/12/2022.
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.