Esophageal NeoplasmsIMPROVENCT02253602
Innovative MRI Techniques to Improve Treatment Stratification of Patients With Esophageal Cancer
A study testing Ferumoxytol in people with Esophageal Neoplasms, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
The current standard treatment of resectable esophageal cancer consists of neoadjuvant chemoradiation followed by resection. However, some patients develop recurrent disease despite chemoradiation and additional (systemic) treatment might have been indicated. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Esophageal Neoplasms
- What is being tested?
- Ferumoxytol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2014to May 2018
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients with biopsy proven esophageal cancer (squamous cell carcinoma or adenocarcinoma)
- Suspected nodal involvement on EUS or CT at diagnosis.
- WHO-performance score 0-2
- Scheduled for surgery
- 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 severe claustrophobia
- Active inflammatory diseases
- History of anaphylaxis or other hypersensitivity reactions
- History of iron overload
- History of abnormal liver function, or elevated liver enzymes (ALAT, ASAT > 3 times upper limit of normal)
- Elevated Serum Transferrin Saturation (TSAT) (>50%) or hemoglobin (>10.5mmol/L)
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center
Amsterdam, North Holland, 1105AZ
About this study
Official title: Innovative MRI Techniques to Improve Treatment Stratification of Patients With Esophageal Cancer: an Optimization and Pilot Study
The current standard treatment of resectable esophageal cancer consists of neoadjuvant chemoradiation followed by resection. However, some patients develop recurrent disease despite chemoradiation and additional (systemic) treatment might have been indicated. Other patients show a (nearly) complete response after chemoradiation and could possibly have been treated with a less extensive treatment regimen. In patients without a threatened circumferential resection margin (CRM) and lymph node metastases chemoradiotherapy could possibly be omitted.
Better stratification of patients with esophageal cancer is therefore urgently needed. Functional magnetic resonance imaging techniques (MRI) can provide in vivo, quantitative information on tumor biology and may prove to be a useful non-invasive tool for this purpose. In this project, ultra-small superparamagnetic particles of iron oxide (USPIO) enhanced MRI using ferumoxytol (Rienso®), diffusion weighted MRI (DWI) and T2* MRI will be developed, both in terms of improvement of acquisition and data processing techniques.
Read the detailed description
The outcome of esophageal cancer is poor, with an overall 5-year survival rate of 10% worldwide. In resectable esophageal cancer, outcome can be improved by multimodality treatment. The current standard treatment of resectable esophageal cancer consists of neoadjuvant chemoradiation followed by resection. In the Netherlands, the preferred chemoradiation regimen consists of carboplatin plus paclitaxel with concurrent radiotherapy in 23 fractions of 1.8 Gray.1 In a meta-analysis the benefit of chemoradiation over surgery alone for both adenocarcinoma and squamous cell carcinoma has been shown.2 However, not all patients benefit from this preoperative treatment regimen. Some patients develop recurrent disease despite chemoradiation and additional (systemic) treatment might have been indicated. In contrast, in other patients a (nearly) complete response is observed after chemoradiation and those patients could possibly have been treated with a less extensive treatment regimen. Furthermore, in patients without a threatened circumferential resection margin (CRM) and lymph node metastases chemoradiotherapy could possibly be omitted, reducing patients' risk for complications and unnecessary, expensive treatment. Thus, stratification of patients with esophageal cancer is urgently needed. Functional magnetic resonance imaging techniques (MRI) can provide in vivo, quantitative information on tumor biology and may prove to be a useful non-invasive tool for this purpose. In this project, ultra-small superparamagnetic particles of iron oxide (USPIO) enhanced MRI using ferumoxytol (Rienso®), diffusion weighted MRI (DWI) and T2* MRI will be developed, both in terms of improvement of acquisition and data processing techniques. For patients with esophageal cancer, the proposed acquisition techniques and data processing have not been performed before.
Objectives of the study
- To determine the optimal acquisition technique for USPIO enhanced MRI and DWI and T2* MRI of esophageal cancer in terms of signal-to-noise ratio, time resolution and spatial resolution.
- To determine the optimal data processing approach for USPIO enhanced MRI, DWI and T2* MRI of esophageal cancer.
- To explore the correlation between lymph node involvement on USPIO enhanced MRI in relation to results obtained at pathological examination.
- To explore the correlation of DWI and T2* MRI of esophageal cancer in relation to stromal involvement and markers of hypoxia and vasculature obtained at pathological examination.
- To explore the accuracy of MRI concerning circumferential tumor delineation compared to pathological examination.
- To determine the feasibility to detect lymph node involvement on USPIO enhanced MRI in initial staging, prior to preoperative chemoradiation therapy.
- To determine the correlation between lymph node involvement on pre-treatment USPIO MRI in relation to results obtained at pathology after complete treatment.
The project will be executed in four steps:
- Optimization of acquisition and data processing techniques of USPIO MRI, DWI and T2* in five healthy volunteers to optimize field of view, number of slices, slice thickness (objectives 1 and 2).
- Assessment of ferumoxytol dose-response with three different dose levels at three different time points in six healthy volunteers (two per dose-level) (objectives 1 and 2).
- Using the data of (1) and (2): assessment of USPIO MRI, DWI and T2* MRI in 20 esophageal cancer patients with clinically suspect lymph nodes directly before surgery (objectives 3, 4 and 5).
- Using the data of (1) and (2): assessment of USPIO MRI, DWI and T2* MRI in 10 esophageal cancer patients with clinically suspect lymph nodes, before initial start of the treatment (objectives 6 and 7).
For step 1 and 2 we aim to include healthy volunteers; for step 3 and 4 we aim to include patients with esophageal cancer.
- Conditions
- Esophageal Neoplasms
- Being tested
- Ferumoxytol
- Keywords
- Esophageal Neoplasms, Lymph Nodes, USPIO, Magnetic Resonance Imaging
- Medical subject headings
- Esophageal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FerumoxytolDrug
Also called USPIO, Rienso
maximum rate of administration 1 ml/sec
| Study group | Role | What they receive |
|---|---|---|
| Ferumoxytol Dose optimization | Experimental | We will assess three different dose levels of Ferumoxytol (4 mg/kg, 6 mg/kg, 8 mg/kg).
Images will be acquired at baseline (before Ferumoxytol administration), during injection of Ferumoxytol and 24, 48 and 72 hours after Ferumoxytol administration to identify the optimal moment of scanning.To assess whether USPIOs are sufficiently cleared within 12 weeks from lymph nodes, the MRI scans will be repeated in all six volunteers at 12 weeks after Ferumoxytol administration. Thus, volunteers will undergo an MRI scan for five times. Ferumoxytol is administered only once Receives: Drug: Ferumoxytol |
| Before Surgery | Experimental | Twenty patients will be measured directly before surgery. Patients will be measured at baseline, during injection of Ferumoxytol and 24, 48 or 72 hours after Ferumoxytol administration, depending on the results of the dose optimization study. MR parameters will be correlated with pathology data. Receives: Drug: Ferumoxytol |
| Before Neoadjucant therapy | Experimental | Ten patients will be measured before start of neoadjuvant chemoradiation. Patients will be measured at baseline, during injection of Ferumoxytol and 24, 48 or 72 hours after Ferumoxytol administration, based on the dose optimization study. MR parameters will be correlated with pathology data. Receives: Drug: Ferumoxytol |
What is being measured
The primary outcome is the main question the study is designed to answer.
USPIO MRI
For USPIO enhanced MRI the main endpoint is the change in T2 and T2* at the tumor and lymph nodes on MRI after the administration of USPIO.
Measured: 24, 48 or 72 hours after USPIO administration
DWI/IVIM MRI
For DWI the main endpoint is the perfusion fraction f and the diffusion coefficient D obtained by IVIM of the primary tumor.
Measured: 1 hour before USPIO administration
T2* MRI
For T2* MRI the main endpoint is T2* of the primary tumor
Measured: 1 hour before USPIO administration
Ferumoxytol dose response
For Ferumoxytol dose evaluation the main endpoint is the change in T2 and T2* at the tumor and lymph nodes on MRI at 24, 48, 72 hours and 12 weeks after the administration of Ferumoxytol.
Measured: 24, 48, 72 hours and 12 weeks after the administration of Ferumoxytol
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2014 (estimated)
- Study startSep 2014
- Primary completionMay 2018
- Study completionMay 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Esophageal NeoplasmsStudies 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
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, H.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
- NCT02253602
- Sponsor's protocol ID
- NL48757.018.14
- Acronym
- IMPROVE
- Status last verified
- Jan 2019
- First submitted
- 4 Sep 2014
- Last updated
- 16 Jan 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Innovative MRI Techniques to Improve Treatment Stratification of Patients With Esophageal Cancer: an Optimization and Pilot Study
- ClinicalTrials.gov ID
- NCT02253602
- Acronym / sponsor ID
- IMPROVE / NL48757.018.14
- Conditions
- Esophageal Neoplasms
- Keywords
- Esophageal Neoplasms, Lymph Nodes, USPIO, Magnetic Resonance Imaging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Study start
- Sep 2014 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- May 2018 (actual)
- First posted
- 1 Oct 2014 (estimated)
- 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.
The current standard treatment of resectable esophageal cancer consists of neoadjuvant chemoradiation followed by resection. However, some patients develop recurrent disease despite chemoradiation and additional (systemic) treatment might have been indicated. Other patients show a (nearly) complete response after chemoradiation and could possibly have been treated with a less extensive treatment regimen. In patients without a threatened circumferential resection margin (CRM) and lymph node metastases chemoradiotherapy could possibly be omitted.
Better stratification of patients with esophageal cancer is therefore urgently needed. Functional magnetic resonance imaging techniques (MRI) can provide in vivo, quantitative information on tumor biology and may prove to be a useful non-invasive tool for this purpose. In this project, ultra-small superparamagnetic particles of iron oxide (USPIO) enhanced MRI using ferumoxytol (Rienso®), diffusion weighted MRI (DWI) and T2* MRI will be developed, both in terms of improvement of acquisition and data processing techniques.
Detailed description
The outcome of esophageal cancer is poor, with an overall 5-year survival rate of 10% worldwide. In resectable esophageal cancer, outcome can be improved by multimodality treatment. The current standard treatment of resectable esophageal cancer consists of neoadjuvant chemoradiation followed by resection. In the Netherlands, the preferred chemoradiation regimen consists of carboplatin plus paclitaxel with concurrent radiotherapy in 23 fractions of 1.8 Gray.1 In a meta-analysis the benefit of chemoradiation over surgery alone for both adenocarcinoma and squamous cell carcinoma has been shown.2 However, not all patients benefit from this preoperative treatment regimen. Some patients develop recurrent disease despite chemoradiation and additional (systemic) treatment might have been indicated. In contrast, in other patients a (nearly) complete response is observed after chemoradiation and those patients could possibly have been treated with a less extensive treatment regimen. Furthermore, in patients without a threatened circumferential resection margin (CRM) and lymph node metastases chemoradiotherapy could possibly be omitted, reducing patients' risk for complications and unnecessary, expensive treatment. Thus, stratification of patients with esophageal cancer is urgently needed. Functional magnetic resonance imaging techniques (MRI) can provide in vivo, quantitative information on tumor biology and may prove to be a useful non-invasive tool for this purpose. In this project, ultra-small superparamagnetic particles of iron oxide (USPIO) enhanced MRI using ferumoxytol (Rienso®), diffusion weighted MRI (DWI) and T2* MRI will be developed, both in terms of improvement of acquisition and data processing techniques. For patients with esophageal cancer, the proposed acquisition techniques and data processing have not been performed before.
Objectives of the study
- To determine the optimal acquisition technique for USPIO enhanced MRI and DWI and T2* MRI of esophageal cancer in terms of signal-to-noise ratio, time resolution and spatial resolution.
- To determine the optimal data processing approach for USPIO enhanced MRI, DWI and T2* MRI of esophageal cancer.
- To explore the correlation between lymph node involvement on USPIO enhanced MRI in relation to results obtained at pathological examination.
- To explore the correlation of DWI and T2* MRI of esophageal cancer in relation to stromal involvement and markers of hypoxia and vasculature obtained at pathological examination.
- To explore the accuracy of MRI concerning circumferential tumor delineation compared to pathological examination.
- To determine the feasibility to detect lymph node involvement on USPIO enhanced MRI in initial staging, prior to preoperative chemoradiation therapy.
- To determine the correlation between lymph node involvement on pre-treatment USPIO MRI in relation to results obtained at pathology after complete treatment.
The project will be executed in four steps:
- Optimization of acquisition and data processing techniques of USPIO MRI, DWI and T2* in five healthy volunteers to optimize field of view, number of slices, slice thickness (objectives 1 and 2).
- Assessment of ferumoxytol dose-response with three different dose levels at three different time points in six healthy volunteers (two per dose-level) (objectives 1 and 2).
- Using the data of (1) and (2): assessment of USPIO MRI, DWI and T2* MRI in 20 esophageal cancer patients with clinically suspect lymph nodes directly before surgery (objectives 3, 4 and 5).
- Using the data of (1) and (2): assessment of USPIO MRI, DWI and T2* MRI in 10 esophageal cancer patients with clinically suspect lymph nodes, before initial start of the treatment (objectives 6 and 7).
For step 1 and 2 we aim to include healthy volunteers; for step 3 and 4 we aim to include patients with esophageal cancer.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ferumoxytol Dose optimization | Experimental | Drug: FerumoxytolWe will assess three different dose levels of Ferumoxytol (4 mg/kg, 6 mg/kg, 8 mg/kg). Images will be acquired at baseline (before Ferumoxytol administration), during injection of Ferumoxytol and 24, 48 and 72 hours after Ferumoxytol administration to identify the optimal moment of scanning.To assess whether USPIOs are sufficiently cleared within 12 weeks from lymph nodes, the MRI scans will be repeated in all six volunteers at 12 weeks after Ferumoxytol administration. Thus, volunteers will undergo an MRI scan for five times. Ferumoxytol is administered only once |
| Before Surgery | Experimental | Drug: FerumoxytolTwenty patients will be measured directly before surgery. Patients will be measured at baseline, during injection of Ferumoxytol and 24, 48 or 72 hours after Ferumoxytol administration, depending on the results of the dose optimization study. MR parameters will be correlated with pathology data. |
| Before Neoadjucant therapy | Experimental | Drug: FerumoxytolTen patients will be measured before start of neoadjuvant chemoradiation. Patients will be measured at baseline, during injection of Ferumoxytol and 24, 48 or 72 hours after Ferumoxytol administration, based on the dose optimization study. MR parameters will be correlated with pathology data. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with biopsy proven esophageal cancer (squamous cell carcinoma or adenocarcinoma)
- Suspected nodal involvement on EUS or CT at diagnosis.
- WHO-performance score 0-2
- Scheduled for surgery
- Written informed consent
Key exclusion criteria (7 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 severe claustrophobia
- Active inflammatory diseases
- History of anaphylaxis or other hypersensitivity reactions
- History of iron overload
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 |
|---|---|---|
| FerumoxytolAlso: USPIO, Riensomaximum rate of administration 1 ml/sec | Drug | Before Neoadjucant therapy, Before Surgery, Ferumoxytol Dose optimization |
Primary outcome
USPIO MRI
Time frame: 24, 48 or 72 hours after USPIO administration
For USPIO enhanced MRI the main endpoint is the change in T2 and T2* at the tumor and lymph nodes on MRI after the administration of USPIO.
DWI/IVIM MRI
Time frame: 1 hour before USPIO administration
For DWI the main endpoint is the perfusion fraction f and the diffusion coefficient D obtained by IVIM of the primary tumor.
T2* MRI
Time frame: 1 hour before USPIO administration
For T2* MRI the main endpoint is T2* of the primary tumor
Ferumoxytol dose response
Time frame: 24, 48, 72 hours and 12 weeks after the administration of Ferumoxytol
For Ferumoxytol dose evaluation the main endpoint is the change in T2 and T2* at the tumor and lymph nodes on MRI at 24, 48, 72 hours and 12 weeks after the administration of Ferumoxytol.
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 16 Jan 2019.
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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.
Hanneke WM van Laarhoven, MD, PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ferumoxytol in people with Esophageal Neoplasms, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site 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 7 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 16 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
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?
USPIO MRI (time frame: 24, 48 or 72 hours after USPIO administration). The study lists 4 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 16 Jan 2019.