To Observe the Benefit of Adding Brachytherapy After CCRT on Resectable Esophageal Cancer Patients Without Surgery

To Observe the Local Tumor Recurrence Rate of Adding Intraluminal Brachytherapy With Balloon Applicator After Standard Definitive Concurrent Chemoradiotherapy (CCRT) on Local-regional Thoracic Esophageal Cancer Patients Who Refused Surgery

Clinical experience of adding intraluminal brachytherapy with traditional applicator after definitive concurrent chemoradiotherapy (CCRT) for local-regional thoracic esophageal cancer is limited due to high complication risk and non-superiority in survival. The innovative applicator can maximize the therapeutic efficacy by reducing dose inhomogeneity in the esophageal wall, which will translate into less over-dosing and less risk of the side effects of fistula or stenosis.

The primary goal of this study by using new applicator is to observe the change in local tumor control rate, while secondary goals are treatment related toxicity, progression-free survival, and overall survival.

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Device: "BRAXX" Esophageal Brachytherapy Applicator; Radiation: Add-on Brachytherapy

Detailed Description

American Brachytherapy Society (ABS) provided guidelines for brachytherapy in esophageal cancer in 1997, which defines the general principle for brachytherapy used in definitive CCRT. (1) Patients with unifocal thoracic adeno- or squamous cancers < or = 10 cm in length, with no evidence of intra-abdominal or metastatic disease.

(2) Contraindications include tracheal or bronchial involvement, cervical esophagus location, or stenosis that cannot be bypassed.

(3) The esophageal brachytherapy applicator should have an external diameter of 6-10 mm.

(4) If 5FU-based chemotherapy and 45-50-Gy EBRT are used, recommended brachytherapy is HDR 5-10 Gy in one to two weekly fractions of 5 Gy each and should not be given concurrently with chemotherapy In the esophageal cancer treatments, tumor recurrence in the primary tumor site approaches 50% in most non-surgical CCRT series reported. Brachytherapy has the advantages of introducing higher doses to the tumor site to improve tumor control, but it is like the double edge of the sword, higher dose may bring higher risk of serious side effect, such as fistula formation in the esophagus noted over previous studies. The innovative Braxx applicator can maximize the therapeutic efficacy by reducing dose inhomogeneity in the esophageal wall (3mm to surface: 136-175%), which will translate into less over-dosing and less risk of the side effects of fistula or stenosis as noted in traditional brachytherapy using NG tube (3mm to surface: 160%-265%). Without much changing the user's habits in performing brachytherapy, the innovative applicator is expected to be easier to be accepted for use.

* Screening Phase: All non-T4b or M1 (non-nodal organ involvement) stage esophageal cancer participants who received neoadjuvant/ definitive chemoradiation first, which includes radiotherapy dosage between 4140-5040cGy concurrently with chemotherapy of carboplatin + paclitaxel or cisplatin + 5FU.

• The evaluation for feasibility of surgery takes place 5-6 weeks after CCRT. Any participant's tumor status is resectable at evaluation but declines surgical proposal will be eligible to be enrolled in the following study phase.

• Eligible participant receives consolidative CCRT, which includes EBRT dosage of 2000cGy concurrently with chemotherapy of carboplatin + paclitaxel or cisplatin + 5FU as the investigators' status quo.

  • Brachytherapy Study Phase:

Brachytherapy protocol starts within 2 weeks after consolidative EBRT (This is "Week 1"), enrolled participants will receive brachytherapy with specified balloon applicator. High-dose-rate (HDR) Nucletron brachytherapy system will be used in the treatment, 5-Gy per fraction is delivered to the pre-treatment esophageal length of primary tumor(s), second treatment if applicable will be finished within 2 weeks after the first one, a total of 5-10Gy in 1-2 fractions will be delivered.

The distance from the center of radiation source to the surface of applicator is 6-9mm depending on the air volume inflated into the balloons in the applicator, the esophageal mucosa will be attached against to the surface of inflated balloon, radiation dose prescribed at 3mm away from the balloon surface will cover most of the esophageal wall, and 5Gy will be prescribed there. Efforts will be made to reduce the high dosage volume in adjacent normal organs, also to reduce the hot spot within treated esophageal wall. It is NOT allowed to give concurrent chemotherapy on the days of HDR brachytherapy. Grade 3 and higher grade toxicity may cause a prolonged interval between the two brachytherapy treatments, either dose reduction or delay treatment according to tolerability of individual participant is allowed. If participant can't tolerate full course of brachytherapy, the total dose (EBRT+brachytherapy) can be reduced to 25Gy without violation of protocol. The management of adverse effects will follow general principles.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Taiwan
  • Taiwan
    • Taoyuan, Taiwan, Taiwan, 33305
      • Linkou Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age of 20-85 years, with ECOG performance 0-2
2. Thoracic esophageal cancer with clinical stage I-III and biopsy proof; patient with cervical esophageal cancer or stage IV thoracic esophageal cancer could be recruited in this trial according to Investigator's assessment.
3. Complete first course CCRT with minimum doses of 40 Gy to tumor and nodal area via external beam radiotherapy (EBRT).
4. Patient whose tumor is resectable but declined to receive surgery after first course CCRT.

Exclusion Criteria:

1. T4b tumor status (tracheal / bronchial mucosa, aortic involvement, or fistula formation).
2. Stenosis of esophageal lumen that cannot be bypassed by the applicator.
3. The primary tumor length exceeds 20cm.
4. The patient is participating in other clinical trials.

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: Add-on Brachytherapy; The evaluation for feasibility of surgery takes place 5-6 weeks after CCRT. Any subject whose tumor status is resectable at evaluation but declines surgical proposal will be eligible to be enrolled in the following study phase.

Device: "BRAXX" Esophageal Brachytherapy Applicator; The device is intended for use with commercially available afterloader during brachytherapy. The purpose of the device is for delivery of radioactive source to the esophagus. This device is sterile, disposable and single-use.; Other Names: 510(K) Number: K183332 (class II); Radiation: Add-on Brachytherapy; Brachytherapy protocol starts within 2 weeks after consolidative EBRT, subjects who are enrolled will receive brachytherapy with specified balloon applicator. High-dose-rate (HDR) brachytherapy system will be used in the treatment, 5-Gy per fraction is delivered to the pre-treatment esophageal length of primary tumor(s), second treatment if applicable will be finished within 2 weeks after the first one, a total of 5-10Gy in 1-2 fractions will be delivered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To estimate the local control rate at primary tumor site	Enrolled subject will be followed every 3 months after treatment, EGD-endoscope (± biopsy) will be arranged at Month 3, 6, 9, 12 and CT scans on Month 6, 12, to evaluate the tumor status.	12 months after completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment toxicity grading according to the CTCAE	Treatment toxicity will be recorded at each visit as CTCAE v5.0.	12 months after completion of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	the tumor status or patient's survival status within 1 year after treatment	12 months after completion of treatment
Overall survival (OS)	patient's survival status within 1 year after treatment	12 months after completion of treatment

Collaborators and Investigators

• Sponsor: Chang Gung Memorial Hospital
• Investigators: Principal Investigator: Chen-Kan Tseng, MD, Chang Gung Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2022
• Primary Completion (Estimated): October 18, 2026
• Study Completion (Estimated): October 18, 2026

Study Registration Dates

• First Submitted: September 3, 2021
• First Submitted That Met QC Criteria: November 22, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• 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
• Other Study ID Numbers: 202100288A3

Drug and device information, study documents

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