Upfront Chemotherapy With Radiation Therapy (CRT) Followed by Chemotherapy in Localized Esophageal Adenocarcinoma (TNT Esophagus)

A Single-arm Study of Upfront Chemotherapy With Radiation Therapy (CRT) Followed by Chemotherapy in Localized Esophageal Adenocarcinoma

The goal of this trial is to learn if adding consolidative chemotherapy to routine chemoradiation can better control both local recurrence and metastasis and reduce the need for surgical intervention.

Study Overview

• Status: Not yet recruiting
• Conditions: Esophageal Adenocarcinoma
• Intervention / Treatment: Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin)

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Office; Phone Number: (919) 668-3726; Email: RadOnc-Clinical_Trials@dm.duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
      • Principal Investigator: Manisha Palta, MD
      • Contact: Kaitlin Bailey, RN BSN OCN; Phone Number: 919-668-3726; Email: RadOnc-Clinical_Trials@dm.duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must be able to provide study specific informed consent prior to study entry
• Must be newly diagnosed, histologically proven diagnosis of adenocarcinoma of the thoracic esophagus or gastroesophageal junction (Siewert I-II);
• Stage II-IVA, excluding T4b, according to the American Joint Committee on Cancer (AJCC) 8th edition;
• Complete history and physical examination within 21 days of signing consent;
• Staging whole-body FDG-PET/CT (fluorodeoxyglucose-positron emission tomography/computed tomography) scan with or without contrast (preferred) or chest/abdominal (CT with contrast) confirming there is no evidence of metastatic disease must be obtained within 45 days of study enrollment
• ECOG (Eastern Cooperative Oncology Group) performance status of 0-2
• Subjects must be appropriate candidates for planned chemoradiation (concurrent carboplatin/paclitaxel) and chemotherapy (FLOT, m-FOLFOX-6) as determined by the treating radiation oncologist, medical oncologist, and surgical oncologist.
• Adequate hematologic, renal, and hepatic function within 14 days of initiation of therapy

Exclusion Criteria:

• Cervical esophageal cancers arising 15-18 cm from the incisors.
• Esophageal squamous cell carcinoma.
• Patients with T4b disease according to the AJCC 8th Edition.
• Definitive clinical or radiologic evidence of metastatic disease.
• Has had prior systemic therapy or radiation therapy for the current diagnosis.
• Prior thoracic radiotherapy for any reason that would result in overlap of radiation therapy fields; all patients with prior radiotherapy must be reviewed by the PI to determine if patient is eligible.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

• Severe, active co-morbidity defined as follows:

  • Active uncontrolled infection requiring IV antibiotics;
  • Pregnant and/or nursing subjects;
  • HIV positive with CD4 count < 200 cells/microliter. Note that subjects who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count ≥ 200 cells/microliter within 30 days prior to registration. Note also that HIV testing is not required for eligibility for this protocol. This exclusion criterion is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
• Has a history or current evidence of physical or physiological contraindication to participation in this study, at the discretion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemoradiation with consolidative chemotherapy; Participants will receive a standard course of chemoradiation followed by consolidative chemotherapy (FOLFOX regimen at the treating physician's discretion).	Drug: FOLFOX (5-fluorouracil, Leucovorin, Oxaliplatin); Modified-FOLFOX-6 or FLOT (Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Clinical complete response (cCR)	cCR defined as absence of malignancy on endoscopic biopsies obtained at the time of reassessment following neoadjuvant therapy	approximately 36 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with pathologic complete response (pCR)	Pathologic complete response (pCR) is defined as absence of detectable tumor of esophagectomy tissues.	approximately 36 weeks
Number of participants who complete both chemoradiation and chemotherapy		approximately 36 weeks
Number of participants with local control	Local control in participants achieving clinical complete remission (cCR) estimated using the Kaplan-Meier method. cCR is defined as the disappearance of all detectable signs and symptoms of a disease, such as cancer, have completely disappeared.	up to 5 years
Number of participants with Disease free survival	Disease free survival in participants achieving cCR estimated using the Kaplan-Meier method. cCR is defined as the disappearance of all detectable signs and symptoms of a disease, such as cancer, have completely disappeared.	up to 5 years
Time to distant metastasis	Time to distant metastasis in participants achieving cCR estimated using the Kaplan-Meier method. cCR is defined as the disappearance of all detectable signs and symptoms of a disease, such as cancer, have completely disappeared.	up to 5 years
Overall survival	Measured in participants achieving cCR and estimated using the Kaplan-Meier method. cCR is defined as the disappearance of all detectable signs and symptoms of a disease, such as cancer, have completely disappeared.	up to 5 years
Number of participants with Local control	Measured in participants achieving pCR and estimated using the Kaplan-Meier method. pCR is defined as absence of detectable tumor of esophagectomy tissues.	up to 5 years
Disease free survival	Disease free survival in participants achieving pCR. pCR is defined as absence of detectable tumor of esophagectomy tissues.	up to 5 years
Time to distant metastasis	Time to distant metastasis in participants achieving pCR estimated using the Kaplan-Meier method. pCR is defined as absence of detectable tumor of esophagectomy tissues.	up to 5 years
Overall survival	Measured in participants achieving pCR and estimated using the Kaplan-Meier method. pCR is defined as absence of detectable tumor of esophagectomy tissues.	up to 5 years

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Manisha Palta, MD, Duke Health

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): February 1, 2034

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 18, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: esophageal cancer; chemoradiation; consolidation chemotherapy; non-metastatic esophageal adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Esophageal Neoplasms; Adenocarcinoma Of Esophagus; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin; Folfox protocol
• Other Study ID Numbers: Pro00120182

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data may be shared 6 months after publication or as required by the journal

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No