Preoperative Image-guided Identification of Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer
PRIDE
3 other identifiers
observational
200
1 country
4
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for all trials
Started Apr 2018
Typical duration for all trials
4 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 30, 2018
CompletedFirst Posted
Study publicly available on registry
March 22, 2018
CompletedStudy Start
First participant enrolled
April 9, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2022
CompletedNovember 16, 2020
November 1, 2020
3.4 years
January 30, 2018
November 13, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Histopathologic response
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 Outcomes (3)
Pathological T- and N-stage
Based on resection specimen (surgery 8-10 weeks after finishing nCRT)
Disease-free survival.
Up to 5-year follow-up
Overall survival.
Up to 5-year follow-up
Study Arms (1)
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)
Interventions
* 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
* 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
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
* 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
Eligibility Criteria
Patients with resectable esophageal or gastroesophageal junction adeno- or squamous cell carcinoma, scheduled to receive neoadjuvant chemoradiotherapy according to the CROSS-regimen
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- UMC Utrechtlead
- University Medical Center Groningencollaborator
- The Netherlands Cancer Institutecollaborator
- Koningin Wilhelmina Fondscollaborator
- Amsterdam UMC, location VUmccollaborator
Study Sites (4)
Amsterdam University Medical Centers, Academic Medical Center
Amsterdam, Netherlands
Antoni van Leeuwenhoek - Netherlands Cancer Institute (NKI-AVL)
Amsterdam, Netherlands
University Medical Center Groningen (UMCG)
Groningen, Netherlands
University Medical Center Utrecht (UMCU)
Utrecht, 3584 CX, Netherlands
Related Publications (1)
Borggreve AS, Mook S, Verheij M, Mul VEM, Bergman JJ, Bartels-Rutten A, Ter Beek LC, Beets-Tan RGH, Bennink RJ, van Berge Henegouwen MI, Brosens LAA, Defize IL, van Dieren JM, Dijkstra H, van Hillegersberg R, Hulshof MC, van Laarhoven HWM, Lam MGEH, van Lier ALHMW, Muijs CT, Nagengast WB, Nederveen AJ, Noordzij W, Plukker JTM, van Rossum PSN, Ruurda JP, van Sandick JW, Weusten BLAM, Voncken FEM, Yakar D, Meijer GJ; PRIDE study group. Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): a multicenter observational study. BMC Cancer. 2018 Oct 20;18(1):1006. doi: 10.1186/s12885-018-4892-6.
PMID: 30342494DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- 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
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- PhD, Clinical Physicist at the Department of Radiation Oncology
Study Record Dates
First Submitted
January 30, 2018
First Posted
March 22, 2018
Study Start
April 9, 2018
Primary Completion
September 1, 2021
Study Completion
January 1, 2022
Last Updated
November 16, 2020
Record last verified: 2020-11