ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03474341
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : August 31, 2018
Sponsor:
Collaborators:
University Medical Center Groningen
The Netherlands Cancer Institute
Koningin Wilhelmina Fonds
Amsterdam University Medical Centers, Academic Medical Center
Information provided by (Responsible Party):
Gert Meijer, UMC Utrecht

Brief Summary:

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.


Condition or disease Intervention/treatment
Esophageal Cancer Esophageal Adenocarcinoma Esophageal Squamous Cell Carcinoma Esophageal Neoplasms Diagnostic Test: MRI Diagnostic Test: PET-CT Diagnostic Test: Endoscopy Diagnostic Test: Blood samples

Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Preoperative Image-guided Identification of Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer
Actual Study Start Date : April 9, 2018
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : January 2021

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
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:
  • Magnetic Resonance Imaging
  • DW-MRI
  • DCE-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:
  • 18-F FDG PET-CT
  • PET

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:
  • Endoscopic assessment
  • EUS

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 Name: ctDNA




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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)

  2. 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).

  3. Overall survival. [ Time Frame: Up to 5-year follow-up ]
    Overall survival based on local follow-up policies.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Criteria

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

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): NCT03474341


Contacts
Contact: Gert J Meijer, PhD 0031 88-75 55555 pride@umcutrecht.nl
Contact: Ingmar L Defize, MD 0031 88-75 55555 i.l.defize-2@umcutrecht.nl

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gert Meijer, PhD, Clinical Physicist at the Department of Radiation Oncology, UMC Utrecht
ClinicalTrials.gov Identifier: NCT03474341     History of Changes
Other Study ID Numbers: NL62881.041.17
Project ID 10291 ( Other Grant/Funding Number: Koningin Wilhelmina Fonds (KWF) Kankerbestrijding )
17-941 ( Other Identifier: Medical Ethical Committee UMC Utrecht )
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: August 31, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Gert Meijer, UMC Utrecht:
Neoadjuvant chemoradiotherapy (nCRT)
Pathologic complete response (pCR)
Magnetic Resonance Imaging (MRI)
PET-CT
Circulating tumor DNA (ctDNA)
endoscopy

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Adenocarcinoma
Esophageal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases