- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05067842
Circulating Tumor DNA (ctDNA) in Locally Advanced Esophageal and Gastroesophageal (GE) Junction Adenocarcinoma (TRACT DNA)
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
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: Medical College of Wisconsin Cancer Center Clinical Trials Office
- Phone Number: 8900 866-680-0505
- Email: cccto@mcw.edu
Study Locations
-
-
Wisconsin
-
Milwaukee, Wisconsin, United States, 53226
- Recruiting
- Froedtert Hospital and the Medical College of Wisconsin
-
Principal Investigator:
- Ben George, MD
-
Contact:
- Ben George, MD
- Phone Number: 414-805-4600
- Email: bgeorge@mcw.edu
-
Sub-Investigator:
- Aditya Shreenivas, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Locally advanced esophageal or gastroesophageal adenocarcinoma
Subjects with diagnosed locally advanced esophageal or gastroesophageal adenocarcinoma.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor response measured by circulating tumor DNA
Time Frame: Baseline, 14 days prior to surgery (approximately 8 months), 1 year, and 2 years
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
R0 Surgical Resection
Time Frame: 2 weeks post surgery
|
This measure is the number of subjects with R0 (negative margin) surgical resection of tumor.
|
2 weeks post surgery
|
Overall Survival
Time Frame: 1 year, 2 years
|
this measure is the number of subjects alive at 1 year and 2 years.
|
1 year, 2 years
|
Recurrence-Free Survival
Time Frame: 1 year
|
This measure is the number of subjects without evidence of recurrent tumor at at 1 year.
|
1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Ben George, MD, Medical College of Wisconsin
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PRO00041977
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Adenocarcinoma Esophagus
-
Lucid Diagnostics, Inc.RecruitingBarrett Esophagus | Barretts Esophagus With Dysplasia | Esophagus AdenocarcinomaUnited States
-
CDx DiagnosticsIcahn School of Medicine at Mount Sinai; NYU Langone Health; University of Kansas... and other collaboratorsCompletedBarrett Esophagus | Esophagus Adenocarcinoma | Esophageal DysplasiaUnited States
-
University of Colorado, DenverRecruitingBarrett Esophagus | Esophageal Adenocarcinoma | Barretts Esophagus With DysplasiaUnited States
-
University of North Carolina, Chapel HillInterpace Diagnostics CorporationCompletedBarretts Esophagus With Dysplasia | Intramucosal AdenocarcinomaUnited States
-
Lucid Diagnostics, Inc.CompletedBarrett Esophagus | Esophageal Adenocarcinoma | Barrett's Esophagus Without Dysplasia | Barretts Esophagus With DysplasiaUnited States, Spain
-
Activ SurgicalWest Penn Allegheny Health System; University of Pittsburgh Medical CenterRecruitingEsophageal Cancer | Esophageal Neoplasms | Esophageal Diseases | Esophageal Adenocarcinoma | Esophageal Squamous Cell Carcinoma | Esophagus Cancer | Esophagus Adenocarcinoma | Esophagus Tumor | Esophagus Neoplasm | Esophagus SCCUnited States
-
City of Hope Medical CenterRecruitingEsophageal Cancer | Esophageal Neoplasms | Gastroesophageal Reflux | Barrett Esophagus | Esophageal Adenocarcinoma | Reflux Disease | Barretts Esophagus With High Grade Dysplasia | Barrett Adenocarcinoma | Esophagus Cancer | Barrett's Esophagus Without Dysplasia | Barretts Esophagus With Dysplasia | Esophagus... and other conditionsUnited States
-
Mayo ClinicTerminatedBarretts Esophagus With High Grade Dysplasia | Barrett AdenocarcinomaUnited States
-
Academisch Medisch Centrum - Universiteit van Amsterdam...UnknownBarrett Esophagus | Adenocarcinoma Esophagus | Submucosal Esophageal Adenocarcinoma | High-risk Mucosal Esophageal AdenocarcinomaFrance, United Kingdom, Belgium, Germany, Switzerland, Australia, Netherlands
-
Mayo ClinicCompletedEarly Esophageal Adenocarcinoma | Barretts Esophagus | High Grade DysplasiaUnited States, Netherlands
Clinical Trials on Circulating tumor DNA(ctDNA) level measurement
-
Medical College of WisconsinWithdrawnRectal CancerUnited States
-
The Netherlands Cancer InstituteJohns Hopkins University; Catharina Ziekenhuis Eindhoven; Amsterdam UMC, location... and other collaboratorsRecruitingOvarian NeoplasmsNetherlands
-
Zhujiang HospitalNot yet recruitingRecurrence | Hepatocellular Carcinoma | Surgery | Circulating Tumor CellChina
-
Christer EricssonKarolinska Institutet; iCellate MedicalUnknownCancer | Neoplasms, Unknown PrimarySweden
-
Zhujiang HospitalRecruitingHepatocellular Carcinoma ResectableChina
-
Rigshospitalet, DenmarkRecruitingGastric Cancer | Esophageal CancerDenmark
-
Helsinki University Central HospitalInstitute for Molecular MedicineUnknown
-
Fudan UniversityRecruiting
-
University Medical Center Ho Chi Minh City (UMC)RecruitingGastric Cancer | Circulating Tumor DNA (ctDNA)Vietnam
-
British Columbia Cancer AgencyUniversity of British Columbia; University of Utah; Pathway Genomics; Boreal GenomicsCompleted