MAESTRO Study: Metabolic Imaging to Improve Patient-Specific Therapy Outcomes

NCT04534543 | Recruiting DMC

• 1 other identifier: Volgt2
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 2

Brief Summary

Patients suffering metastasized gastrointestinal cancer often receive ineffective treatments for prolonged periods of time as therapy non-response, which is hard to detect, cannot be determined earlier than nine weeks following start of therapy. Current therapy evaluation strategies primarily focus on morphological changes via RECIST criteria. However, morphological changes are subjected to prior physiological and metabolic alterations. Therefore, the MAESTRO project's ambition is to lay the foundations of a new area of research: the study of human biology using non-invasive chemistry imaging. For this, MAESTRO aims to unite two areas of research: metabolomics and magnetic resonance (MR). Metabolomics studies body functions through the measurements of metabolites; MR imaging (MRI) and spectroscopy (MRS) can provide 3D images of the body and measure metabolite and lipid content respectively. Previous studies show that phospholipid metabolites in particular the cell membrane precursors i.e. phosphomonoesters (PME), and the cell membrane degradation products i.e. phosphodiesters (PDE) are valuable biomarkers in therapy assessment. With this MAESTRO approach, the consortium aims at reducing the nine weeks period before therapy efficacy evaluation to three weeks or less. By validating the powerful new MRS(I)-visible biomarkers in a patient cohort, a non-invasive technology can be developed for dynamically mapping biochemical processes in the whole human body and pave the way for individualized medicine.

Conditions

Gastrointestinal Cancer Metastatic

Keywords

gastrointestinal cancer; human biology; non-invasive chemistry imaging; MR imaging; spectroscopy

Outcome Measures

Primary Outcomes (2)

• PME/PDE-ratio from Area Under the Curve (AUC): predictive

  The primary outcome measure in this study is the PME/PDE-ratio (PME/PDE) resulting from the AUC of the metabolite peaks in the acquired metabolic images e.g. spectra. This measure is used to calculate changes in the metabolic phospholipid-ratios of PME and PDE (ΔPME/PDE) between baseline and after 2 weeks of therapy. In addition, this outcome measure is used to investigate secondary objectives including PME/PDE at baseline as a sole predictor (see Outcome Measure 3).

  72 months

• Change in PME/PDE (ΔPME/PDE): predictive

  The second primary outcome measure to investigate the discriminative ability of PME/PDE is the ΔPME/PDE between baseline and after 2 weeks of therapy. This measure is used to investigate the primary objective whether biochemical imaging of change in the metabolic phospholipid-ratios of PME and PDE (ΔPME/PDE) between baseline and after 2 weeks of therapy are predictive for RECIST progression in gastrointestinal cancer patients after the first 9 week treatment period. In addition, this outcome measure is also used to investigate secondary objectives which includes different time periods over which ΔPME/PDE is measured.

  72 months

Secondary Outcomes (4)

• PME/PDE at baseline: predictive

  72 months

• Prediction model

  72 months

• (Δ)PME/PDE predictive significance

  72 months

• Response to treatment

  72 months

Study Arms (1)

Imaging

OTHER

Participants will undergo multiple 7T MR imaging sessions which include advanced 31P MRSI techniques, before start of palliative chemotherapy and during treatment until progression of disease or until week 54.

Radiation: MRI/Spectroscopy

Interventions

MRI/Spectroscopy RADIATION

Participants will undergo multiple 7T MR imaging sessions which include advanced 31P MRSI techniques, before start of palliative chemotherapy and during treatment until progression of disease or until week 54.

Imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with liver metastasis of gastrointestinal cancer, with histological or cytological proof of metastasis or a high suspicion on CT imaging.
• Tumour size ≥ 1cm.
• WHO-performance score 0-2.
• Scheduled for first- or second-line palliative chemotherapy containing capecitabine combined with oxaliplatin (CAPOX) or fluorouracil combined with oxaliplatin and folinic acid (FOLFOX).
• Written informed consent.

You may not qualify if:

• Any psychological, familial, sociological, or geographical condition potentially hampering adequate informed consent or compliance with the study protocol.
• Contra-indications for MR scanning, including patients with a pacemaker, cochlear implant or neurostimulator; patients with non-MR compatible metallic implants in their eye, spine, thorax or abdomen; or a non-MR compatible aneurysm clip in their brain; patients with claustrophobia.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• UMC Utrecht: collaborator

Study Sites (2)

Amsterdam UMC

Amsterdam, Netherlands

RECRUITING

UMC Utrecht

Utrecht, Netherlands

RECRUITING

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Hanneke WM van Laarhoven, MD PhD

  Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sebastiaan Siegerink, PhD

CONTACT

0623674312; s.n.siegerink@amsterdamumc.nl

Hanneke WM van Laarhoven, MD PhD

CONTACT

020-5665955; hvanlaarhoven@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the Department of Medical Oncology, Clinical Professor

Model Details: • In this study we will investigate whether biochemical imaging of change (Δ, figure 1) in the metabolic phospholipid ratios of PME and PDE between baseline and after 2 weeks of therapy are predictive for RECIST progression in gastrointestinal cancer patients after the first 9 week treatment period.

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: September 1, 2020
• Study Start: December 15, 2021
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: August 2, 2024

Record last verified: 2024-08

Locations

NL (2)