NCT02125448

Brief Summary

Rationale: For resectable esophageal cancer the standard therapy is 5 weeks of neoadjuvant chemoradiotherapy (nCRT) followed by surgery 6-8 weeks afterwards. Surgery is performed independent of the response to nCRT and is associated with substantial morbidity. A pathological complete response (pCR) after nCRT is seen in 28-34% of patients. Pathological non-responders (pNR) most probably do not benefit from nCRT but are exposed to its toxicity and delay from surgical therapy inevitably occurs in this group. Early identification of non-responders during nCRT would allow individualized decision making in continuation or discontinuation of nCRT. Furthermore, a tool is desirable to accurately assess the treatment response after nCRT to identify patients with a complete response. Studies in rectal cancer reported that tumor resection could be omitted in patients with persisting clinical complete response after 12 months. Also, in some esophageal cancer studies, complete responders in surgical and non-surgical treatment groups had comparable overall survival. These findings indicate the possibility to perform nCRT as sole treatment in patients with a complete response. Conversely, if residual tumor is demonstrated, this will support the decision to move to surgery. Objective: Diagnostic study to assess the distinct and combined value of anatomical and functional magnetic resonance imaging (MRI) and combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography (PET-CT) in the evaluation of treatment response to nCRT for patients with esophageal cancer. Study design: Multi-center diagnostic study investigating the value of MRI and PET-CT in the imaging before, during and after nCRT for assessment of response to nCRT for resectable esophageal cancer. Imaging response measurements will be compared with the histopathological tumor regression grade (TRG) of the resection specimen as gold standard. Study population: 50 patients (\>18 years) presenting at the UMC Utrecht or M.D. Anderson Cancer Center with resectable esophageal cancer, as determined by endoscopy and biopsy, computed tomography (CT) and endoscopic ultrasonography (EUS), receiving nCRT prior to surgery. Procedure: In addition to the conventional diagnostic work-up for esophageal cancer including a standard PET-CT before nCRT, two PET-CT scans will be performed during and after nCRT as well as three MRI scans before, during and after nCRT at the same time points. The first MRI (and standard-of-care PET-CT) scan session will be within the 6 weeks prior to the start of nCRT. The second scan session will take place after 10-14 days after the start of nCRT. The third and final scan session will be planned 1-2 weeks before surgery. Main study parameters/endpoints: Determination of the distinct and combined diagnostic value of anatomical and functional MRI and PET-CT in the evaluation of treatment response to nCRT for patients with esophageal cancer. Important imaging parameters include apparent diffusion coefficient (ADC) values, standardized uptake values (SUV) and volume measurements for the different time points. The differences of these values between time points are of particular interest (delta-ADC, delta-SUV, delta-volume). The sensitivity (%), specificity (%), negative predictive value (%), positive predictive value (%), and accuracy (%) of the different imaging parameters for correctly identifying histopathological complete response will be calculated.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Oct 2013

Typical duration for all trials

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2013

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

December 5, 2013

Completed
5 months until next milestone

First Posted

Study publicly available on registry

April 29, 2014

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2016

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
Last Updated

November 16, 2020

Status Verified

November 1, 2020

Enrollment Period

2.8 years

First QC Date

December 5, 2013

Last Update Submit

November 13, 2020

Conditions

Esophageal Cancer

Keywords

Esophageal cancerMRIPET-CTResponse assessment

Outcome Measures

Primary Outcomes (1)

  • Distinct and combined sensitivity, specificity, predictive values, and accuracy of MRI and PET-CT for identifying histopathological complete response.

    Exploration of the distinct and combined value of anatomical and functional MRI and PET-CT in the evaluation of treatment response to neoadjuvant chemoradiotherapy for resectable esophageal cancer, as compared to the pathological specimen as gold standard. The sensitivity (%), specificity (%), negative predictive value (%), positive predictive value (%), and accuracy (%) of the different imaging parameters for correctly identifying histopathological complete response will be calculated.

    Histopathological tumor regression grade (TRG) as determined in the first week after surgical resection, which will be performed 6-8 after completion of neoadjuvant chemoradiotherapy.

Secondary Outcomes (2)

  • Post-treatment TN-staging accuracy.

    Histopathological TN-stage as determined in the first week after surgical resection, which will be performed 6-8 weeks after neoadjuvant chemoradiotherapy.

  • Experienced patient burden (UMC Utrecht only).

    Immediately after the third MRI and PET-CT scanning session (on the same day), which will take place 1-2 weeks before surgical resection.

Study Arms (1)

Resectable esophageal cancer

Neoadjuvant chemoradiotherapy. MRI and PET-CT.

Device: MRI and PET-CT

Interventions

MRI and PET-CTDEVICE
Also known as: Diffusion-weighted imaging., Dynamic contrast-enhanced MRI., FDG-PET, PET
Resectable esophageal cancer

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
Study Population

The research population consists of patients with resectable esophageal carcinoma, scheduled to receive preoperative chemoradiation according to the CROSS-regimen. The participants will be recruited from the surgical outpatient clinic or the radiation oncology department of the UMC Utrecht or M.D. Anderson Cancer Center. In total 50 participants with available histopathologic data of the resection specimen are required for this study.

You may qualify if:

  • Histologically confirmed squamous-cell carcinoma, adenocarcinoma or large-cell undifferentiated carcinoma of the esophagus or esophagogastric junction (i.e. tumors involving both cardia and esophagus on endoscopy)
  • Potentially resectable tumor (cT1b-4a N0-3 M0): based on standard primary staging by EUS and CT
  • Undergoing preoperative chemoradiation according to CROSS-regimen
  • Age\>18 years
  • No history of other cancer or previous radiotherapy or chemotherapy
  • Signed informed consent

You may not qualify if:

  • Patients with insulin dependent diabetes mellitus or blood plasma glucose concentration higher than 10 mmol/L
  • Patients with a known Gadovist allergy
  • Patients with a known CT-contrast allergy
  • Patients having difficulty understanding Dutch
  • Pregnant or breast-feeding patients

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University Medical Center Utrecht

Utrecht, 3584CX, Netherlands

Location

Related Links

Biospecimen

Retention: SAMPLES WITH DNA

At the UMC Utrecht, the resection specimens after esophagectomy will be kept in our institute's biobank, according to standard clinical practice. At M.D. Anderson Cancer Center biopsy and blood samples will be collected for all patients.

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Positron Emission Tomography Computed TomographyDiffusion Magnetic Resonance ImagingDynamic Contrast Enhanced Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Gastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsHead and Neck NeoplasmsDigestive System DiseasesEsophageal DiseasesGastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Positron-Emission TomographyTomography, Emission-ComputedImage Interpretation, Computer-AssistedDiagnostic ImagingDiagnostic Techniques and ProceduresDiagnosisTomography, X-Ray ComputedMultimodal ImagingRadiographic Image EnhancementImage EnhancementPhotographyRadiographyTomography, X-RayRadionuclide ImagingTomographyDiagnostic Techniques, RadioisotopeMagnetic Resonance Imaging

Study Officials

  • Gert J Meijer, PhD

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

  • Jelle P Ruurda, MD, PhD

    UMC Utrecht

    PRINCIPAL INVESTIGATOR

  • Steven H Lin, MD, PhD

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
PhD

Study Record Dates

First Submitted

December 5, 2013

First Posted

April 29, 2014

Study Start

October 1, 2013

Primary Completion

August 1, 2016

Study Completion

November 1, 2016

Last Updated

November 16, 2020

Record last verified: 2020-11

Locations

US(1)NL(1)