Preoperative Image-guided Identification of Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer (PRIDE)

November 13, 2020 updated by: Gert Meijer, UMC Utrecht

Rationale: For locally advanced esophageal cancer the standard treatment consists of 5 weeks of neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Surgery is currently performed independent of the response to nCRT and is associated with substantial morbidity. Prior knowledge of the eventual response to nCRT would greatly impact on the optimal care for many esophageal cancer patients for two imperative reasons:

Firstly, it is argued that patients who achieved a pathologic complete response (pCR, 29%) may not have benefitted from surgery. Consequently, proper identification of pathological complete responders prior to surgery could yield an organ-preserving regimen avoiding unnecessary toxicity.

Secondly, non-responders are exposed to the side effects of nCRT without showing any tumor regression. Early identification of the non-responders during nCRT would be beneficial for this group as ineffective therapy could be stopped, and for who altered treatment strategies could be explored.

Objective: To develop a multimodal model that predicts the probability of pathologic complete response to nCRT in esophageal cancer, by integrating diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in conjunction with combined 18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) scans acquired prior to, during and after administration of nCRT.

Study design: Multi-center observational study

Study population: Patients (>18 years) with potentially resectable locally advanced squamous cell- or adenocarcinoma of the esophagus or gastroesophageal junction, receiving nCRT prior to surgery.

Intervention: In addition to the standard diagnostic work-up for esophageal cancer that includes a 18F-FDG PET-CT scan at diagnosis and after nCRT, one 18F-FDG PET-CT scans will be performed during nCRT, as well as three MRI scans (before, during and after nCRT) within fixed time intervals. Furthermore, after response imaging after nCRT has been performed, but prior to surgery, patients will undergo (on an opt-out basis) an endoscopy and/or endoscopic ultrasonography (EUS) with biopsies of the primary tumor site, other suspected lesions and suspected lymph nodes. Furthermore, blood samples will be collected at three time points.

Main study parameters/endpoints: An accurate multimodal prediction model for the patients' individual probability of pathologic complete response after nCRT, based on the quantitative parameters derived from a longitudinal series of DW-MRI, DCE-MRI and 18F-FDG PET-CT datasets.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Amsterdam University Medical Centers, Academic Medical Center
        • Contact:
          • Hanneke WM van Laarhoven, MD, PhD
      • Amsterdam, Netherlands
        • Not yet recruiting
        • Antoni van Leeuwenhoek - Netherlands Cancer Institute (NKI-AVL)
        • Contact:
          • Marcel Verheij, MD, PhD
      • Groningen, Netherlands
        • Recruiting
        • University Medical Center Groningen (UMCG)
        • Contact:
          • J. (Hans) A. Langendijk, MD, PhD
      • Utrecht, Netherlands, 3584 CX
        • Recruiting
        • University Medical Center Utrecht (UMCU)
        • Contact:
          • Gert Meijer, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with resectable esophageal or gastroesophageal junction adeno- or squamous cell carcinoma, scheduled to receive neoadjuvant chemoradiotherapy according to the CROSS-regimen

Description

Inclusion Criteria:

  • Histologically confirmed squamous cell carcinoma or adenocarcinoma of the esophagus or gastroesophageal junction (i.e. tumors involving both cardia and esophagus on endoscopy)
  • Potentially resectable locally advanced esophageal tumor (cT1b-4a N0-3 M0): based on standard primary staging by EUS and 18F-FDG PET-CT
  • Scheduled to receive neoadjuvant chemoradiotherapy according to CROSS-regimen1: weekly administration of carboplatin and paclitaxel for 5 weeks and concurrent radiotherapy (41.4 Gray in 23 fractions, 5 days per week) followed by esophagectomy
  • Age > 18 years

Exclusion Criteria:

  • Patients who meet exclusion criteria for MRI

  • Patients who meet exclusion criteria for intravenous gadolinium-based contrast:

    • Glomerular Filtration Rate (GFR) of <30 mL/min/1.73m2
    • Nephrogenic Systemic Fibrosis (strict contra-indication for gadolinium-based contrast)
    • Known allergy for gadolinium-based contrast
  • Patients with a blood plasma glucose concentration >10 mmol/L or poorly controlled diabetes mellitus
  • Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) of primary tumor prior to start of neoadjuvant chemoradiotherapy
  • Pregnant or breast-feeding patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Resectable esophageal squamous cell- or adenocarcinoma

Patients (>18 years) with potentially resectable locally advanced squamous cell- or adenocarcinoma of the esophagus or gastroesophageal junction, receiving nCRT according to the CROSS regimen prior to surgery.

CROSS regimen: weekly carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, delivered 5 days per week on workdays with intensity modulated radiotherapy, including photon and proton therapy)
Diagnostic test: MRI
  • Anatomical (T2W) and functional MRI (DWI and DCE) at a 1.5T Siemens or Philips scanner
  • DWI series: sagittal (sIVIM) and high-resolution transversal (HR tDWI)
  • DCE serie: dynamic20
  • In total, three MRI scan series (before, during, after nCRT)
  • Measurements: i.a. change in apparent diffusion coefficient (ADC) or area-under-the-gadolinium-concentration time curve (AUC) within tumor delineation over time, radiological (qualitative) assessment of residual disease
Other Names:
  • DCE-MRI
  • Magnetic Resonance Imaging
  • DW-MRI
  • T2W
Diagnostic test: PET-CT
  • According to European Association of Nuclear Medicine (EANM) Research Ltd guidelines (EARL)
  • In total one additional PET-CT (during nCRT) for study purposes. A PET-CT scan at diagnosis and after nCRT are included in the standard diagnostic work-up for esophageal cancer.
  • Measurements: i.a. change in TLG (Total Lesion Glycolysis), SUVmax (Standardized Uptake Value) or Ktrans within tumor delineation over time
Other Names:
  • PET
  • 18-F FDG PET-CT
Diagnostic test: Endoscopy
Additional endoscopy and/or endoscopic ultrasonography (EUS) with biopsies of the primary tumor site and other suspected lesions in the esophagus after completion of nCRT and prior to surgery
Other Names:
  • EUS
  • Endoscopic assessment
Diagnostic test: Blood samples
  • Blood samples at three different time points (before, during and after nCRT) will be collected
  • Blood will be collected in cell-free DNA collection tubes
  • Purpose: isolation of ctDNA and subsequent mutation analysis by means of Next Generation Sequencing
  • Measurements: the presence of, and changes in, ctDNA during nCRT
Other Names:
  • ctDNA

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Histopathologic response
Time Frame: Based on resection specimen (surgery 8-10 weeks after finishing nCRT)

Histopathologic response of the primary tumor to nCRT according to the tumor regression grade (TRG) scale as determined by expert pathologist.

TRG 1: no residual viable tumor cells, pathologic complete response TRG 2: rare residual cancer cells TRG 3: predominant fibrosis with increased number of residual cancer cells TRG 4: residual cancer outgrowing fibrosis or no regressive change
Based on resection specimen (surgery 8-10 weeks after finishing nCRT)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pathological T- and N-stage
Time Frame: Based on resection specimen (surgery 8-10 weeks after finishing nCRT)
Pathological T- and N-stage as determined by expert pathologist (based on the American Joint Committee on Cancer [AJCC] Tumor Node Metastasis [TNM] staging system)
Based on resection specimen (surgery 8-10 weeks after finishing nCRT)
Disease-free survival.
Time Frame: Up to 5-year follow-up
Disease-free survival based on local follow-up policies (time to locoregional or distal recurrence of esophageal cancer).
Up to 5-year follow-up
Overall survival.
Time Frame: Up to 5-year follow-up
Overall survival based on local follow-up policies.
Up to 5-year follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UMC Utrecht

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University Medical Center Groningen
Amsterdam UMC, location VUmc
The Netherlands Cancer Institute
Koningin Wilhelmina Fonds

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gert J Meijer, PhD, UMC Utrecht
  • Principal Investigator: Marcel Verheij, MD, PhD, Antoni van Leeuwenhoek - Netherlands Cancer Institute
  • Principal Investigator: J. (Hans) A. Langendijk, MD, PhD, University Medical Center Groningen
  • Principal Investigator: Hanneke WM van Laarhoven, MD, PhD, Amsterdam UMC, location VUmc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 9, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2021

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 30, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 21, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 22, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 16, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 13, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • NL62881.041.17
  • Project ID 10291 (OTHER_GRANT: Koningin Wilhelmina Fonds (KWF) Kankerbestrijding)
  • 17-941 (OTHER: Medical Ethical Committee UMC Utrecht)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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