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

NCT05067842 | Withdrawn

• 1 other identifier: PRO00041977
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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 \[50.4 Gray (Gy) over approximately six weeks with concurrent radio sensitizing dose of carboplatin/paclitaxel\].

Conditions

Adenocarcinoma Esophagus

Keywords

Adenocarcinoma; Esophagus; Gastroesophageal Junction; Chemotherapy; Chemoradiation

Outcome Measures

Primary Outcomes (1)

• Tumor response measured by circulating tumor DNA

  This measure will quantify ctDNA concentration expressed in mean tumor molecules (MTM)/ml. Measurements will be made at Baseline, 8 weeks, 16 weeks, 14 days before surgery (approximately 8 months), 14 days after surgery, and every three months in follow-up up to 2 years. Results will be reported at Baseline, 14 days prior to surgery (approximately 8 months), 1 year, and 2 years.

  Baseline, 14 days prior to surgery (approximately 8 months), 1 year, and 2 years

Secondary Outcomes (3)

• R0 Surgical Resection

  2 weeks post surgery

• Overall Survival

  1 year, 2 years

• Recurrence-Free Survival

  1 year

Study Arms (1)

Locally advanced esophageal or gastroesophageal adenocarcinoma

Subjects with diagnosed locally advanced esophageal or gastroesophageal adenocarcinoma.

Diagnostic Test: Circulating tumor DNA(ctDNA) level measurement

Interventions

Circulating tumor DNA(ctDNA) level measurement DIAGNOSTIC_TEST

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.

Locally advanced esophageal or gastroesophageal adenocarcinoma

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will enroll male and female subjects with diagnosed esophageal or gastroesophageal adenocarcinoma between the ages of 18 and 80 years of age.

You may qualify if:

• Ability to understand a written informed consent document, and the willingness to sign and date it.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Male or female between the ages of 18 and 80 years.
• Newly diagnosed, clinically advanced T3-T4 or node-positive adenocarcinoma of esophagus or gastroesophageal junction as assessed by PET/CT or CT of the chest, abdomen and pelvis and/or by endoscopic ultrasound, with pathologic diagnosis obtained within one month of signing consent, without delivery of prior chemotherapy or radiation therapy.
• Subjects must be previously untreated with systemic chemotherapy or radiation therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
• Adequate bone marrow function: white blood cell (WBC) count \> 3 x 10\^9/L; hemoglobin \> 8 g/dL; platelets \> 100 x 10\^9/L.
• Adequate liver function: total bilirubin \< 1.5 x upper limit of normal; aspartate aminotransferase (AST) \< 3 x upper limit of normal (ULN); alanine aminotransferase (ALT) \< 3 x upper limit of normal); serum creatinine \< 1.5 x ULN.
• Women and men of childbearing age should use contraceptives throughout the treatment period of the study.
• Ability to obtain tissue sample for ctDNA analysis and detectable baseline ctDNA level.
• Concurrent participation in other clinical studies that will not affect the general sequence of therapies in the trial schema of this study would be allowed.
• Adjuvant chemotherapy or immunotherapy would be allowed as this is an observational study and would be at clinician's discretion.

You may not qualify if:

• Subjects with metastatic gastric or gastroesophageal junction adenocarcinoma.
• Subjects with esophageal or gastroesophageal junction squamous cell carcinoma or adeno-squamous carcinoma.
• Prior treatment with chemotherapy or radiation therapy for gastric or gastroesophageal adenocarcinoma.
• Subjects that received treatment for a second primary malignancy within one year of screening will be excluded, however pts. with h/o early-stage cancers treated with curative intent, including basal or squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast would be eligible.
• Subjects with greater than grade 2 peripheral neuropathy.
• Any serious or uncontrolled medical disorder or active infection, which in the opinion of the investigator may increase the risk associated with study participation, study treatment administration, or would impair the ability of the subject to receive study treatment.
• Known history of active hepatitis B or hepatitis C.
• Clinically unstable cardiac disease, including unstable angina, congestive heart failure, ventricular arrhythmia.
• History of allergy or hypersensitivity to any of the study drugs or study drug components.
• Contraindications to any of the study drugs of the chemotherapy regimens selected by the investigator.
• Known history of dihydropyridine dehydrogenase (DPD) deficiency.
• Female patients who are pregnant, nursing or lactating.

Sponsors & Collaborators

• Medical College of Wisconsin: lead

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Adenocarcinoma Of Esophagus; Adenocarcinoma

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Ben George, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 24, 2021
• First Posted: October 5, 2021
• Study Start: May 13, 2022
• Primary Completion: May 30, 2025
• Study Completion: May 30, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)