NSCLC, Stage IIIAPROLUNGNCT03736993
Metabolomics Predict Therapy Response
A study testing Additional blood sampling in people with NSCLC, Stage IIIA, run by Hasselt University at 4 sites in Belgium.
Trial summary
Complete resection is the mainstay of treatment for stage I-IIIA resectable non-small cell lung cancer (NSCLC). However rates of recurrence of disease are high, with five-year survival rates ranging between 73% (stage IA) and 24% (stage IIIA). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- NSCLC, Stage IIIA
- What is being tested?
- Additional blood sampling
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 4 sitesBelgium
- Study dates
- 28 May 2018to 31 Dec 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a stage I-IIIA NSCLC tumor, eligible to undergo surgery
- Signed written informed consent
Who cannot join
- No fasting starting from 22:00 h the day prior to blood sampling
- Medication intake in the morning of the blood sampling
- Non-controlled diabetes
- History of cancer during the past 5 years
- Treatment for cancer during the past 5 years
Trial locations and contacts
4 sites in 1 country.
Belgium4 sites
OLV ziekenhuis Aalst
Aalst
Ziekenhuis Oost-Limburg
Genk, 3600
UZ Gent
Ghent, 9000
AZ Delta
Roeselare, 8800
About this study
Official title: Towards Better Therapy for Resectable Lung Cancer: Metabolomics Predict Therapy Response
Complete resection is the mainstay of treatment for stage I-IIIA resectable non-small cell lung cancer (NSCLC). However rates of recurrence of disease are high, with five-year survival rates ranging between 73% (stage IA) and 24% (stage IIIA). Therefore, a prognostic biological marker that stratifies between NSCLC patients whom surgery cures versus patients in whom surgery would be futile due to early disease relapse after surgery is eagerly awaited.
The primary objective of this prospective study is to establish a prognostic marker of early disease progression after complete surgical resection in patients with stages I to IIIA NSCLC. For this purpose the investigator will compare the metabolic profile with disease progression or death within one year after complete surgical resection to the patients with a progression free survival. Furthermore the investigator will evaluate the changes in the metabolic profile after surgery and if changes in this metabolic profile over time can predict disease recurrence before it becomes clinically apparent.
Read the detailed description
Introduction: Precision medicine relies on validated biomarkers that can accurately classify patients by their probable disease risk, prognosis and/or response to treatment. Metabolomics is particularly promising for biomarker development because altered metabolism is considered a hallmark of cancer. The measurement of the metabolomic plasma profile is cheap (+-50 EUR) and fast (+-17 min), with a high information throughput on a per sample base.
Rationale: Complete resection is the mainstay of treatment for stage I-IIIA resectable non-small cell lung cancer (NSCLC). However rates of recurrence of disease are high, with five-year survival rates ranging between 73% (stage IA) and 24% (stage IIIA). Therefore, a prognostic biological marker that stratifies between NSCLC patients whom surgery cures versus patients in whom surgery would be futile due to early disease relapse after surgery is eagerly awaited.
Study objective: The primary study hypothesis is that the metabolic plasma profile is a predictive marker of early disease progression after complete surgical resection in patients with pathological stages I to IIIA NSCLC. The secondary study hypothesis is that the level of dissimilarity between the metabolic profile before surgery and the metabolic profile after surgery, is a predictor for disease recurrence (in which the extreme case would be, that a normalization of the metabolic profile to the profile of a healthy person, is indicative of a good prognosis).
Study design: Prospective, interventional design
Study population: Stage I-IIIA NSCLC patients who will undergo complete surgical resection willing to provide a written informed consent.
Number of patients: 200 patients with stage I-IIIA NSCLC who will undergo thoracic surgery with a curative intent will be included.
Main study parameters/endpoints: Recurrence free survival, overall survival, metabolic phenotype, presence or absence of hot-spot mutations in tested proto-oncogenes and tumor suppressor genes in circulating tumor DNA (ctDNA) in blood plasma, the tumor tissue and possibly positive lymph nodes, 43 items of the EORTC quality of life questionnaire C30 and LC13.
Nature and extent of the burden and risks associated with participation: Subjects will be asked to give consent to take 10-30 ml of blood at several moments throughout the disease course and in follow-up. Furthermore, the participants need to give their permission to use the resected tumor/lymph node tissue for genetic testing. Clinical parameters will be pooled in a database in a confidential way.
- Conditions
- NSCLC, Stage IIIA
- Being tested
- Additional blood sampling
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Additional blood samplingOther
Establish predictive markers for early disease progression after complete surgical resection in patients with stage I to IIIA NSCLC.
| Study group | Role | What they receive |
|---|---|---|
| Additional blood sampling | Other | non-small cell lung cancer (NSCLC) Receives: Other: Additional blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
The metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR)
The metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR) spectroscopy predicts disease disease recurrence within one year after surgical resection.
Measured: baseline
Secondary outcomes (4)
Change in the metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR)
The degree of change in the metabolic profile in plasma before and after surgery correlates with the risk for early disease recurrence.
Measured: screening, day 1, week 1, week 4, week 6, week 12, week 52
Change in ctDNA mutations in plasma
The degree of change in ctDNA mutations in plasma before and after surgery correlates with the risk for early disease recurrence.
Measured: day 1, week 12, week 52
Correlation between presence or absence Hotspot mutations and the metabolic profile in plasma
A specific metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR) spectroscopy correlates with the presence of absence of certain ctDNA mutations in plasma
Measured: day 1, week 12, week 52
Metabolic profile of the primary tumor
The metabolic profile of the primary tumor correlates with the metabolic profile in plasma
Measured: day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2018
- Study start28 May 2018
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for NSCLC, Stage IIIAStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 160 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hasselt University
- Sponsor type
- University, hospital or other
- Collaborators
- Ziekenhuis Oost-Limburg
- Responsible party
- Principal investigator, Prof. dr. Michiel Thomeer, Hasselt University
- Investigators
- Michiel Thomeer, prof. dr., Principal investigator, Hasselt UniversityElien Derveaux, drs., Study chair, Hasselt UniversityLiesbet Mesotten, prof. dr., Study chair, Hasselt Universitypeter Adriaensens, prof. dr., Study chair, Hasselt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03736993
- Sponsor's protocol ID
- PROLUNG001
- Acronym
- PROLUNG
- Status last verified
- Dec 2023
- First submitted
- 17 Aug 2018
- Last updated
- 15 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: still no plan for, but open for sharing after discussion with participating groups
Publications
Louis E, Cantrelle FX, Mesotten L, Reekmans G, Bervoets L, Vanhove K, Thomeer M, Lippens G, Adriaensens P. Metabolic phenotyping of human plasma by 1 H-NMR at high and medium magnetic field strengths: a case study for lung cancer. Magn Reson Chem. 2017 Aug;55(8):706-713. doi: 10.1002/mrc.4577. Epub 2017 Feb 27.
PubMed 28061019Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmuller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R; for "Precision Medicine and Pharmacometabolomics Task Group"-Metabolomics Society Initiative. Metabolomics enables precision medicine: "A White Paper, Community Perspective". Metabolomics. 2016;12(10):149. doi: 10.1007/s11306-016-1094-6. Epub 2016 Sep 2.
PubMed 27642271Beger RD. A review of applications of metabolomics in cancer. Metabolites. 2013 Jul 5;3(3):552-74. doi: 10.3390/metabo3030552.
PubMed 24958139Louis E, Adriaensens P, Guedens W, Bigirumurame T, Baeten K, Vanhove K, Vandeurzen K, Darquennes K, Vansteenkiste J, Dooms C, Shkedy Z, Mesotten L, Thomeer M. Detection of Lung Cancer through Metabolic Changes Measured in Blood Plasma. J Thorac Oncol. 2016 Apr;11(4):516-23. doi: 10.1016/j.jtho.2016.01.011. Epub 2016 Feb 29.
PubMed 26949046Louis E, Adriaensens P, Guedens W, Vanhove K, Vandeurzen K, Darquennes K, Vansteenkiste J, Dooms C, de Jonge E, Thomeer M, Mesotten L. Metabolic phenotyping of human blood plasma: a powerful tool to discriminate between cancer types? Ann Oncol. 2016 Jan;27(1):178-84. doi: 10.1093/annonc/mdv499. Epub 2015 Oct 20.
PubMed 26487580
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Towards Better Therapy for Resectable Lung Cancer: Metabolomics Predict Therapy Response
- ClinicalTrials.gov ID
- NCT03736993
- Acronym / sponsor ID
- PROLUNG / PROLUNG001
- Conditions
- NSCLC, Stage IIIA
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 160 participants (actual)
- Lead sponsor
- Hasselt UniversityUniversity, hospital or other
- Collaborators
- Ziekenhuis Oost-Limburg
- Study start
- 28 May 2018 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 9 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Complete resection is the mainstay of treatment for stage I-IIIA resectable non-small cell lung cancer (NSCLC). However rates of recurrence of disease are high, with five-year survival rates ranging between 73% (stage IA) and 24% (stage IIIA). Therefore, a prognostic biological marker that stratifies between NSCLC patients whom surgery cures versus patients in whom surgery would be futile due to early disease relapse after surgery is eagerly awaited.
The primary objective of this prospective study is to establish a prognostic marker of early disease progression after complete surgical resection in patients with stages I to IIIA NSCLC. For this purpose the investigator will compare the metabolic profile with disease progression or death within one year after complete surgical resection to the patients with a progression free survival. Furthermore the investigator will evaluate the changes in the metabolic profile after surgery and if changes in this metabolic profile over time can predict disease recurrence before it becomes clinically apparent.
Detailed description
Introduction: Precision medicine relies on validated biomarkers that can accurately classify patients by their probable disease risk, prognosis and/or response to treatment. Metabolomics is particularly promising for biomarker development because altered metabolism is considered a hallmark of cancer. The measurement of the metabolomic plasma profile is cheap (+-50 EUR) and fast (+-17 min), with a high information throughput on a per sample base.
Rationale: Complete resection is the mainstay of treatment for stage I-IIIA resectable non-small cell lung cancer (NSCLC). However rates of recurrence of disease are high, with five-year survival rates ranging between 73% (stage IA) and 24% (stage IIIA). Therefore, a prognostic biological marker that stratifies between NSCLC patients whom surgery cures versus patients in whom surgery would be futile due to early disease relapse after surgery is eagerly awaited.
Study objective: The primary study hypothesis is that the metabolic plasma profile is a predictive marker of early disease progression after complete surgical resection in patients with pathological stages I to IIIA NSCLC. The secondary study hypothesis is that the level of dissimilarity between the metabolic profile before surgery and the metabolic profile after surgery, is a predictor for disease recurrence (in which the extreme case would be, that a normalization of the metabolic profile to the profile of a healthy person, is indicative of a good prognosis).
Study design: Prospective, interventional design
Study population: Stage I-IIIA NSCLC patients who will undergo complete surgical resection willing to provide a written informed consent.
Number of patients: 200 patients with stage I-IIIA NSCLC who will undergo thoracic surgery with a curative intent will be included.
Main study parameters/endpoints: Recurrence free survival, overall survival, metabolic phenotype, presence or absence of hot-spot mutations in tested proto-oncogenes and tumor suppressor genes in circulating tumor DNA (ctDNA) in blood plasma, the tumor tissue and possibly positive lymph nodes, 43 items of the EORTC quality of life questionnaire C30 and LC13.
Nature and extent of the burden and risks associated with participation: Subjects will be asked to give consent to take 10-30 ml of blood at several moments throughout the disease course and in follow-up. Furthermore, the participants need to give their permission to use the resected tumor/lymph node tissue for genetic testing. Clinical parameters will be pooled in a database in a confidential way.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Additional blood sampling | Other | Other: Additional blood samplingnon-small cell lung cancer (NSCLC) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with a stage I-IIIA NSCLC tumor, eligible to undergo surgery
- Signed written informed consent
Key exclusion criteria (5 listed)
- No fasting starting from 22:00 h the day prior to blood sampling
- Medication intake in the morning of the blood sampling
- Non-controlled diabetes
- History of cancer during the past 5 years
- Treatment for cancer during the past 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Additional blood samplingEstablish predictive markers for early disease progression after complete surgical resection in patients with stage I to IIIA NSCLC. | Other | Additional blood sampling |
Primary outcome
The metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR)
Time frame: baseline
The metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR) spectroscopy predicts disease disease recurrence within one year after surgical resection.
4 secondary outcomes
Change in the metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR)
Time frame: screening, day 1, week 1, week 4, week 6, week 12, week 52
Change in ctDNA mutations in plasma
Time frame: day 1, week 12, week 52
Correlation between presence or absence Hotspot mutations and the metabolic profile in plasma
Time frame: day 1, week 12, week 52
Metabolic profile of the primary tumor
Time frame: day 1
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
- Background: PubMed 28061019Louis E, Cantrelle FX, Mesotten L, Reekmans G, Bervoets L, Vanhove K, Thomeer M, Lippens G, Adriaensens P. Metabolic phenotyping of human plasma by 1 H-NMR at high and medium magnetic field strengths: a case study for lung cancer. Magn Reson Chem. 2017 Aug;55(8):706-713. doi: 10.1002/mrc.4577. Epub 2017 Feb 27.
- Background: PubMed 27642271Beger RD, Dunn W, Schmidt MA, Gross SS, Kirwan JA, Cascante M, Brennan L, Wishart DS, Oresic M, Hankemeier T, Broadhurst DI, Lane AN, Suhre K, Kastenmuller G, Sumner SJ, Thiele I, Fiehn O, Kaddurah-Daouk R; for "Precision Medicine and Pharmacometabolomics Task Group"-Metabolomics Society Initiative. Metabolomics enables precision medicine: "A White Paper, Community Perspective". Metabolomics. 2016;12(10):149. doi: 10.1007/s11306-016-1094-6. Epub 2016 Sep 2.
- Background: PubMed 24958139Beger RD. A review of applications of metabolomics in cancer. Metabolites. 2013 Jul 5;3(3):552-74. doi: 10.3390/metabo3030552.
- Results publication: PubMed 26949046Louis E, Adriaensens P, Guedens W, Bigirumurame T, Baeten K, Vanhove K, Vandeurzen K, Darquennes K, Vansteenkiste J, Dooms C, Shkedy Z, Mesotten L, Thomeer M. Detection of Lung Cancer through Metabolic Changes Measured in Blood Plasma. J Thorac Oncol. 2016 Apr;11(4):516-23. doi: 10.1016/j.jtho.2016.01.011. Epub 2016 Feb 29.
- Results publication: PubMed 26487580Louis E, Adriaensens P, Guedens W, Vanhove K, Vandeurzen K, Darquennes K, Vansteenkiste J, Dooms C, de Jonge E, Thomeer M, Mesotten L. Metabolic phenotyping of human blood plasma: a powerful tool to discriminate between cancer types? Ann Oncol. 2016 Jan;27(1):178-84. doi: 10.1093/annonc/mdv499. Epub 2015 Oct 20.
- Individual participant dataSharing planned: Undecided. still no plan for, but open for sharing after discussion with participating groups
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michiel Thomeer, prof. dr. principal investigator
Hasselt University
Elien Derveaux, drs. study chair
Hasselt University
Liesbet Mesotten, prof. dr. study chair
Hasselt University
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Additional blood sampling in people with NSCLC, Stage IIIA, run by Hasselt University at 4 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The metabolic profile in plasma measured by Nuclear Magnetic Resonance (NMR) (time frame: baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03736993, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2023.