Gastrointestinal Cancer MetastaticMAESTRONCT04534543
MAESTRO Study: Metabolic Imaging to Improve Patient-Specific Therapy Outcomes
A study testing MRI/Spectroscopy in people with Gastrointestinal Cancer Metastatic, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 2 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Gastrointestinal Cancer Metastatic
- What is being tested?
- MRI/Spectroscopy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 2 sitesNetherlands
- Study dates
- 15 Dec 2021to 1 Feb 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 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.
Who cannot join
- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands2 sites, 2 recruiting
- Recruiting
Amsterdam UMC
Amsterdam
Hanneke van Laarhoven, MD, PhD, PhD
- Recruiting
UMC Utrecht
Utrecht
Dennis Klomp
About this study
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.
Read the detailed description
Primary objective
-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 progression free survival (PFS) and/or overall survival (OS) in gastro-oesophageal cancer patients within 27 weeks of treatment.
Secondary objectives:
- 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 gastro-oesophageal cancer patients after the first 9 week treatment period.
- Investigate whether biochemical imaging of the metabolic phospholipid ratios of PME and PDE at baseline of therapy are predictive for RECIST progression after the first 9-week treatment period, and for PFS and OS in gastro-oesophageal cancer patients.
- Investigate whether biochemical imaging of change (δ, figure 1) in the metabolic phospholipid ratios of PME and PDE after a 9-week treatment period are predictive for RECIST progression following that treatment period, and for PFS and OS in gastro-oesophageal cancer patients.
- Exploratory multi variable analysis for the development of a prediction model to predict resistance to treatment within 3 weeks after the start of chemotherapy with the use of all chemistry imaging data including all MR detectable nuclei and clinical parameters.
Study population: We aim to include a total of 70 patients with metastatic gastro-oesophageal cancer before start of palliative chemotherapy.
Intervention: 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 9.
Main study parameters/endpoints: Study parameters include; metabolic ratios of the phospholipids PME and PDE from the area under the curve (AUC) of the corresponding spectral peaks, size measurements from CT and MRI scans, coded radiology reports, clinical patient data, e.g. chemotherapy details extracted from clinical notes which are coded before storage to preserve anonymity. Main endpoint is defined by progression or death after 27 weeks measured using the RECIST progression criteria for which chemical imaging its predictive value is investigated in the primary objective.
Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Patients will be asked for three extra hospital visits to undergo 7T MRI of approximately one hour per session (3x 1 hour). MRI is a safe non-invasive technique without use of ionizing radiation and so far, extensive research has not shown any side-effects of the high magnetic field used in 7T MRI, resulting in low inherent risks for the participants. This study will be started only after approval of the IGJ and the medical device investigation agency of the AMC. Patients' therapy is not delayed by participation in this study and patients with MRI contraindications are excluded from participation.
- Conditions
- Gastrointestinal Cancer Metastatic
- Being tested
- MRI/Spectroscopy
- Keywords
- gastrointestinal cancer, human biology, non-invasive chemistry imaging, MR imaging, spectroscopy
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI/SpectroscopyRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: MRI/Spectroscopy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 72 months
Secondary outcomes (4)
PME/PDE at baseline: predictive
This secondary measure is used investigate the secondary objective whether biochemical imaging of PME/PDE at baseline of therapy is predictive for RECIST progression after the first 9-week treatment period, and for PFS and OS in gastrointestinal cancer patients. PME/PDE at baseline results from the AUC of the metabolite peaks in the acquired metabolic images e.g. specta (see also Outcome Measure 1).
Measured: 72 months
Prediction model
Exploratory multi variable analysis for the development of a prediction model to predict resistance to treatment within 3 weeks after the start of chemotherapy with the use of all chemistry imaging data including all MR detectable nuclei and clinical parameters.
Multi-variable analysis of clinically relevant data to investigate the feasibility of a dynamic prediction model will use all chemical imaging data, size measurements from CT, conventional 7T MR imaging scans, coded radiology reports, clinical patient data, e.g. chemotherapy details extracted from clinical notes which are coded before storage to preserve anonymity, choice of therapy, progression free survival (PFS) and overall survival (OS) and metastasis origin.
Measured: 72 months
(Δ)PME/PDE predictive significance
To investigate to what extent baseline PME/PDE and (ΔPME/PDE) over all different time periods is predictive of PFS and OS, we will use standard survival analysis techniques (e.g. Cox regression, accelerated failure time models) and estimate the C-index as measure of discriminative ability.
Measured: 72 months
Response to treatment
This outcome measure results from conventional therapy evaluation defined by RECIST progression. It is used in the primary and secondary objectives as the gold standard for the therapy evaluation predictors assessed in this study (ΔPME/PDE, PME/PDE, etc.)
Measured: 72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2020
- Study start15 Dec 2021
- Primary completion1 Feb 2027 (estimated)
- Study completion1 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastrointestinal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- • 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.
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- UMC Utrecht
- Responsible party
- Principal investigator, Hanneke W. M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Hanneke WM van Laarhoven, MD PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04534543
- Sponsor's protocol ID
- Volgt2
- Acronym
- MAESTRO
- Status last verified
- Aug 2024
- First submitted
- 21 Jul 2020
- Last updated
- 2 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MAESTRO Study: Metabolic Imaging to Improve Patient-Specific Therapy Outcomes
- ClinicalTrials.gov ID
- NCT04534543
- Acronym / sponsor ID
- MAESTRO / Volgt2
- Conditions
- Gastrointestinal Cancer Metastatic
- Keywords
- gastrointestinal cancer, human biology, non-invasive chemistry imaging, MR imaging, spectroscopy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- UMC Utrecht
- Study start
- 15 Dec 2021 (actual)
- Primary completion
- 1 Feb 2027 (estimated)
- Study completion
- 1 Feb 2027 (estimated)
- First posted
- 1 Sep 2020 (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.
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.
Detailed description
Primary objective
-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 progression free survival (PFS) and/or overall survival (OS) in gastro-oesophageal cancer patients within 27 weeks of treatment.
Secondary objectives:
- 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 gastro-oesophageal cancer patients after the first 9 week treatment period.
- Investigate whether biochemical imaging of the metabolic phospholipid ratios of PME and PDE at baseline of therapy are predictive for RECIST progression after the first 9-week treatment period, and for PFS and OS in gastro-oesophageal cancer patients.
- Investigate whether biochemical imaging of change (δ, figure 1) in the metabolic phospholipid ratios of PME and PDE after a 9-week treatment period are predictive for RECIST progression following that treatment period, and for PFS and OS in gastro-oesophageal cancer patients.
- Exploratory multi variable analysis for the development of a prediction model to predict resistance to treatment within 3 weeks after the start of chemotherapy with the use of all chemistry imaging data including all MR detectable nuclei and clinical parameters.
Study population: We aim to include a total of 70 patients with metastatic gastro-oesophageal cancer before start of palliative chemotherapy.
Intervention: 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 9.
Main study parameters/endpoints: Study parameters include; metabolic ratios of the phospholipids PME and PDE from the area under the curve (AUC) of the corresponding spectral peaks, size measurements from CT and MRI scans, coded radiology reports, clinical patient data, e.g. chemotherapy details extracted from clinical notes which are coded before storage to preserve anonymity. Main endpoint is defined by progression or death after 27 weeks measured using the RECIST progression criteria for which chemical imaging its predictive value is investigated in the primary objective.
Nature and extent of the burden and risks associated with participation, benefit, and group relatedness: Patients will be asked for three extra hospital visits to undergo 7T MRI of approximately one hour per session (3x 1 hour). MRI is a safe non-invasive technique without use of ionizing radiation and so far, extensive research has not shown any side-effects of the high magnetic field used in 7T MRI, resulting in low inherent risks for the participants. This study will be started only after approval of the IGJ and the medical device investigation agency of the AMC. Patients' therapy is not delayed by participation in this study and patients with MRI contraindications are excluded from participation.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- • 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.
| Arm | Type | Receives |
|---|---|---|
| Imaging | Other | Radiation: MRI/SpectroscopyParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
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 |
|---|---|---|
| MRI/SpectroscopyParticipants 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 | Imaging |
Primary outcome
PME/PDE-ratio from Area Under the Curve (AUC): predictive
Time frame: 72 months
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).
Change in PME/PDE (ΔPME/PDE): predictive
Time frame: 72 months
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.
4 secondary outcomes
PME/PDE at baseline: predictive
Time frame: 72 months
Prediction model
Time frame: 72 months
(Δ)PME/PDE predictive significance
Time frame: 72 months
Response to treatment
Time frame: 72 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2024.
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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.
Hanneke WM van Laarhoven, MD PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRI/Spectroscopy in people with Gastrointestinal Cancer Metastatic, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 2 sites in Netherlands.
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 5 inclusion and 2 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: looking for participants now, as of the sponsor's last update on 2 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Sebastiaan Siegerink, PhD (0623674312, s.n.siegerink@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PME/PDE-ratio from Area Under the Curve (AUC): predictive (time frame: 72 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Aug 2024.