Preoperative Image-guided Identification of Response to Neoadjuvant Chemoradiotherapy in Esophageal Cancer (PRIDE)
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|ClinicalTrials.gov Identifier: NCT03474341|
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : August 31, 2018
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|
|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|
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
Diagnostic Test: 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
Diagnostic Test: Blood samples
Other Name: ctDNA
- 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
- 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)
- 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).
- Overall survival. [ Time Frame: Up to 5-year follow-up ]Overall survival based on local follow-up policies.
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
|Contact: Gert J Meijer, PhD||0031 88-75 email@example.com|
|Contact: Ingmar L Defize, MD||0031 88-75 firstname.lastname@example.org|
|Amsterdam University Medical Centers, Academic Medical Center||Recruiting|
|Contact: Hanneke WM van Laarhoven, MD, PhD|
|Antoni van Leeuwenhoek - Netherlands Cancer Institute (NKI-AVL)||Not yet recruiting|
|Contact: Marcel Verheij, MD, PhD|
|University Medical Center Groningen (UMCG)||Recruiting|
|Contact: J. (Hans) A. Langendijk, MD, PhD|
|University Medical Center Utrecht (UMCU)||Recruiting|
|Utrecht, Netherlands, 3584 CX|
|Contact: Gert Meijer, PhD|
|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|