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Trial record 4 of 386 for:    Recruiting, Not yet recruiting, Available Studies | "Esophageal Neoplasms"

Innovative MRI Techniques to Improve Treatment Stratification of Patients With Esophageal Cancer (IMPROVE)

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ClinicalTrials.gov Identifier: NCT02253602
Recruitment Status : Recruiting
First Posted : October 1, 2014
Last Update Posted : July 27, 2016
Sponsor:
Information provided by (Responsible Party):
H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Esophageal Neoplasms Drug: Ferumoxytol Not Applicable

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

  1. 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.
  2. To determine the optimal data processing approach for USPIO enhanced MRI, DWI and T2* MRI of esophageal cancer.
  3. To explore the correlation between lymph node involvement on USPIO enhanced MRI in relation to results obtained at pathological examination.
  4. 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.
  5. To explore the accuracy of MRI concerning circumferential tumor delineation compared to pathological examination.
  6. To determine the feasibility to detect lymph node involvement on USPIO enhanced MRI in initial staging, prior to preoperative chemoradiation therapy.
  7. 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:

  1. 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).
  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).
  3. 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).
  4. 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Innovative MRI Techniques to Improve Treatment Stratification of Patients With Esophageal Cancer: an Optimization and Pilot Study
Study Start Date : September 2014
Estimated Primary Completion Date : May 2018
Estimated Study Completion Date : May 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Ferumoxytol

Arm Intervention/treatment
Experimental: Ferumoxytol Dose optimization

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

Drug: Ferumoxytol
maximum rate of administration 1 ml/sec
Other Names:
  • USPIO
  • Rienso

Experimental: Before Surgery
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.
Drug: Ferumoxytol
maximum rate of administration 1 ml/sec
Other Names:
  • USPIO
  • Rienso

Experimental: Before Neoadjucant therapy
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.
Drug: Ferumoxytol
maximum rate of administration 1 ml/sec
Other Names:
  • USPIO
  • Rienso




Primary Outcome Measures :
  1. 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.

  2. 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.

  3. T2* MRI [ Time Frame: 1 hour before USPIO administration ]
    For T2* MRI the main endpoint is T2* of the primary tumor

  4. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02253602


Locations
Netherlands
Academic Medical Center Recruiting
Amsterdam, Noord Holland, Netherlands, 1105AZ
Contact: Hanneke WM van Laarhoven, MD, PhD    0031 20 5665955    h.vanlaarhoven@amc.uva.nl   
Principal Investigator: Hanneke WM van Laarhoven, MD, PhD         
Sponsors and Collaborators
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Investigators
Principal Investigator: Hanneke WM van Laarhoven, MD, PhD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Responsible Party: H.W.M. van Laarhoven, MD, PhD, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
ClinicalTrials.gov Identifier: NCT02253602     History of Changes
Other Study ID Numbers: NL48757.018.14
First Posted: October 1, 2014    Key Record Dates
Last Update Posted: July 27, 2016
Last Verified: July 2016

Keywords provided by H.W.M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA):
Esophageal Neoplasms
Lymph Nodes
USPIO
Magnetic Resonance Imaging

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Ferrosoferric Oxide
Hematinics
Parenteral Nutrition Solutions
Pharmaceutical Solutions