NCT05067842

Circulating Tumor DNA (ctDNA) in Locally Advanced Esophageal and Gastroesophageal (GE) Junction Adenocarcinoma

A Pilot Observational Study to Assess Feasibility of Tumor Response Assessment by Circulating Tumor DNA (ctDNA) in Patients With Locally Advanced Esophageal and GE Junction Adenocarcinoma Undergoing Treatment With Total Upfront Chemotherapy and Chemoradiation

• Status: Withdrawn
• Phase: —
• Study type: Observational
• Enrollment: 0 (actual)
• Sponsor: Medical College of Wisconsin · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

This is an observational study to determine the feasibility of assessing tumor response utilizing ctDNA in patients of locally advanced esophageal and gastroesophageal junction (LA-EA/GEJ) cancer undergoing total neoadjuvant therapy (TNT) consisting of systemic chemotherapy (modified FOLFOX or FLOT/DFOX) followed by concurrent chemoradiation \[50.4 Gray (Gy) over approximately six weeks with concurrent radio sensitizing dose of carboplatin/paclitaxel\].

Detailed description

This study will explore the feasibility of assessing tumor response utilizing ctDNA in patients of Locally Advanced Esophageal and Gastroesophageal Junction Adenocarcinoma (LA-EA/GEJ) undergoing TNT consisting of systemic chemotherapy (modified FOLFOX or FLOT/DFOX) followed by concurrent chemoradiation (50.4 Gy over approximately six weeks with concurrent radio sensitizing dose of carboplatin/paclitaxel). The study schema in the following section illustrates the study design. In this observational study, patients with LA -EA/GEJ ca who are selected for the standard-of-care TNT will be enrolled. After obtaining informed consent, a venous blood sample and the archival tissue block from the initial diagnostic tumor biopsy will be sent to the Natera Inc. Patients that have an excellent response (defined by \>35% reduction in standardized uptake value (SUV) max on PET scan) from four cycles of standard-of-care induction chemotherapy (FOLFOX, DFOX or FLOT) will be treated with four additional cycles of therapy followed by chemoradiation and then assessed for curative intent surgery. Patients who receive four cycles of neoadjuvant chemotherapy and don't have an excellent clinical response on the PET scan will not receive additional induction chemotherapy. They will be started on chemoradiation (50.4 Gy, radiation dose at radiation oncologists discretion with concurrent weekly carboplatin and paclitaxel) followed by assessment for surgery. Dose adjustment of radiation and chemotherapy will be allowed as per standard of care. Additional blood samples will be obtained for subsequent ctDNA measurements (after four cycles of neoadjuvant chemotherapy within +/- five days of the imaging study; after eight cycles for PET responders only; after the completion of chemoradiation around one to 14 days before surgery and 10 to 14 days after surgery). All patients may also choose to undergo additional serial ctDNA level measurements for surveillance after the surgery every three months for two years (optional). Tumor response rate assessed by ctDNA will be compared with the response rate assessed by standard methods (PET scan, endoscopic ultrasound or CT/MRI) at different time points to explore if a significant correlation exists between these two response assessment methods. Imaging studies will also be discussed in the tumor board. If preliminary data support the hypothesis that peripheral blood ctDNA can be utilized for tumor response assessment in this scenario, a larger study will be conducted to validate this method. Once validated, ctDNA measurement can potentially supplement other expensive, uncomfortable, and time-consuming methods of tumor response assessment, such as endoscopic ultrasound and PET/CT. This study does not involve any investigational therapeutic intervention. The only intervention planned in this study is obtaining multiple peripheral venous blood samples at prespecified time points described above for ctDNA level measurements.

Conditions

• Adenocarcinoma Esophagus

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	Circulating tumor DNA(ctDNA) level measurement	The ctDNA level will be measured using the Signatera platform developed by Natera, Inc. Signatera is a patient-specific, tumor informed custom-built ctDNA monitoring assay.

Timeline

• Start date: 2022-05-13
• Primary completion: 2025-05-30
• Completion: 2025-05-30
• First posted: 2021-10-05
• Last updated: 2025-06-08

Locations

1 site across 1 country: United States