Metabolomics Predict Therapy Response (PROLUNG)

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.

Study Overview

• Status: Completed
• Conditions: NSCLC, Stage IIIA
• Intervention / Treatment: Other: Additional blood sampling

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 Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
    • OLV Ziekenhuis Aalst
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg
  • Gent, Belgium, 9000
    • Uz Gent
  • Roeselare, Belgium, 8800
    • AZ Delta

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients with a stage I-IIIA NSCLC tumor, eligible to undergo surgery
2. Signed written informed consent

Exclusion Criteria:

1. No fasting starting from 22:00 h the day prior to blood sampling
2. Medication intake in the morning of the blood sampling
3. Non-controlled diabetes
4. History of cancer during the past 5 years
5. Treatment for cancer during the past 5 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Additional blood sampling; non-small cell lung cancer (NSCLC)	Other: Additional blood sampling; Establish predictive markers for early disease progression after complete surgical resection in patients with stage I to IIIA NSCLC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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	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	day 1

Collaborators and Investigators

• Sponsor: Hasselt University
• Collaborators: Ziekenhuis Oost-Limburg
• Investigators: Principal Investigator: Michiel Thomeer, prof. dr., Hasselt University; Study Chair: Elien Derveaux, drs., Hasselt University; Study Chair: Liesbet Mesotten, prof. dr., Hasselt University; Study Chair: peter Adriaensens, prof. dr., Hasselt University

Publications and helpful links

General 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.
• Beger 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.
• Beger RD. A review of applications of metabolomics in cancer. Metabolites. 2013 Jul 5;3(3):552-74. doi: 10.3390/metabo3030552.
• Louis 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.
• Louis 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2018
• Primary Completion (Actual): December 31, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: August 17, 2018
• First Submitted That Met QC Criteria: November 7, 2018
• First Posted (Actual): November 9, 2018

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 14, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: PROLUNG001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: still no plan for, but open for sharing after discussion with participating groups

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No