Metabolomics Predict Therapy Response

NSCLC, Stage IIIA Clinical Trial

— PROLUNG  

Official title:

Towards Better Therapy for Resectable Lung Cancer: Metabolomics Predict Therapy Response

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03736993
• Other study ID #: PROLUNG001
• Status: Completed
• Phase: N/A
• Start date: May 28, 2018
• Est. completion date: December 31, 2022

Study information

• Verified date: December 2023
• Source: Hasselt University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: December 31, 2022
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• NSCLC, Stage IIIA

Intervention

Other:
• Additional blood sampling
Establish predictive markers for early disease progression after complete surgical resection in patients with stage I to IIIA NSCLC.

Locations

Country	Name	City	State
Belgium	OLV ziekenhuis Aalst	Aalst
Belgium	Ziekenhuis Oost-Limburg	Genk
Belgium	UZ Gent	Gent
Belgium	AZ Delta	Roeselare

Sponsors (2)

Lead Sponsor	Collaborator
Hasselt University	Ziekenhuis Oost-Limburg

Country where clinical trial is conducted

Belgium, 

References & Publications (5)

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. — View Citation

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

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. 201 — View Citation

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;2 — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Metabolic profile of the primary tumor	The metabolic profile of the primary tumor correlates with the metabolic profile in plasma	day 1