A Randomized Controlled Trial Evaluating of Prophylactic Irradiation in CRT for cT1bN0M0 ESCC (ARMADILLO)

A Randomized Controlled Phase III Trial of Comparing Local Field With Additional Prophylactic Irradiation in Chemoradiotherapy for Clinical-T1bN0M0 Esophageal Cancer

This study is conducted to investigate whether modified chemoradiotherapy with elective nodal irradiation reduces the locoregional recurrence that cannot be completely resected by salvage endoscopic resection and preserve esophagus without compromising overall survival.

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Radiation: Chemoradiotherapy

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Motoo Nomura, MD/PhD; Phone Number: 81335422511; Email: mnomura@kuhp.kyoto-u.ac.jp

Study Locations

• Japan
  • Tokyo, Japan
    • Recruiting
    • National Cancer Center Hospital
    • Contact: Ken Kato, M.D./Ph.D

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Histologically proven squamous cell carcinoma, adenosquamous carcinoma, or basaloid cell carcinoma.
2. All lesions located in the thoracic esophagus. Secondary lesions with an absolute indication for endoscopic resection (EMR/ESD) may not be confined to the thoracic esophagus.
3. Clinical N0M0 with cervical to abdominal contrast-enhanced CT.
4. The deepest lesion is diagnosed as cT1b (SM1 / SM2 / SM3) with upper gastrointestinal endoscopy. If it is difficult to differentiate cT1a-MM and cT1b-SM1 clinically, the wall depth is diagnosed as cT1b-SM1.
5. Aged 20 years and older.
6. ECOG Performance status 0 or 1.
7. No previous therapy against esophageal cancer except for complete resection by EMR/ESD with either pT1a-LPM (pM2) / pT1a-MM (M3) disease or pT1a-MM (M3) disease without vascular infiltration.
8. No history of radiotherapy for the neck, chest, and upper abdomen for any cancers. No chemotherapy or hormone therapy with less than 3 years of disease-free interval for any cancers.
9. Major organ function is preserved. 1) WBC<=12,000/mm3 2) ANC>=1,500/mm3 3) Hb>=10.0 g /dL 4) PLT>=10,000/mm3 5) T-bil<=1.5 mg /dL 6) AST<=100 IU/L 7) ALT<=100 IU/L 8) SpO2>=95% 9) Ccr>=60 mL/min
10. Patients do not have a preference to receive a surgical resection as an initial therapy after receiving explanations.
11. Written informed consent is obtained.

Exclusion criteria:

1. Simultaneous or metachronous (within 5 years) double cancers, except for intramucosal tumor curable with local therapy.
2. Active infection requiring systemic therapy.
3. Fever over 38 degrees Celsius
4. Female during pregnancy, within 28 days of post parturition, or during lactation. Male who wants a partner's pregnancy.
5. Psychological disorder, which is difficult to participate in this clinical study.
6. Receiving continuous systemic corticosteroid or immunosuppressant treatment.
7. Positive for HBs antigen or HIV antigen.
8. Diabetes mellitus, which is uncontrollable with continuous use of insulin or hypoglycemic agents.
9. Uncontrolled arterial hypertension.
10. History of unstable angina pectoris within three weeks or myocardial infarction within six months before registration.
11. Uncontrolled valvular disease, dilated cardiomyopathy, and hypertrophic cardiomyopathy.
12. Severe emphysema, interstitial pneumonia or pulmonary fibrosis based on chest CT.
13. With a history of cerebrovascular disorder within 6 months.
14. Drug allergy for iodic drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemoradiation therapy with elective nodal irradiation; Chemoradiotherapy consists of 5-FU (1,000 mg / m2, day1-4, day29-32), CDDP (75 mg /m2, day1, 29) and radiotherapy (50.4 Gy/28Fr)	Radiation: Chemoradiotherapy; Chemoradiotherapy
Active Comparator: Chemoradiation therapy with involved field irradiation; Chemoradiotherapy consists of 5-FU (700 mg /m2, day1-4, day29-32), CDDP (70 mg /m2, day1,29) and radiotherapy (60 Gy/30Fr)	Radiation: Chemoradiotherapy; Chemoradiotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major progression-free survival	If the remnant lesion in the esophagus or a recurrent lesion after complete response (CR) can be curatively removed by salvage EMR/ESD, it is not an event, and other progressions and deaths are events.	The primary analysis will be held 5-years after the last patient was enrolled.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	From date of randomization to date of death, approximately 5 years.	The primary analysis will be held 5-years after the last patient was enrolled.
Progression-free survival	From date of randomization to date of progression or death, whichever occurs first, approximately 5 years.	The primary analysis will be held 5-years after the last patient was enrolled.
Complete response rate	CR was defined as disappeared primary tumors without the presence of ulceration or malignant cells in biopsy specimens under endoscopy.	The primary analysis will be held 5-years after the last patient was enrolled.
Esophagectomy-free survival	From date of randomization to date of esophagectomy or death, whichever occurs first, approximately 5 years.	The primary analysis will be held 5-years after the last patient was enrolled.
Adverse events	Number of participants with treatment-related adverse events during CRT as assessed by CTCAE v4.0	The primary analysis will be held 5-years after the last patient was enrolled.
Long term toxicity	Number of participants with treatment-related adverse events after termination of CRT as assessed by CTCAE v4.0	The primary analysis will be held 5-years after the last patient was enrolled.

Collaborators and Investigators

• Sponsor: National Cancer Center, Japan
• Investigators: Study Chair: Ken Kato, MD/PhD, National Cancer Center Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 29, 2020
• First Posted (Actual): April 1, 2020

Study Record Updates

• Last Update Posted (Actual): May 22, 2025
• Last Update Submitted That Met QC Criteria: May 19, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Esophageal squamous cell carcinoma; chemoradiotherapy; Radiation Field
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Carcinoma, Squamous Cell
• Other Study ID Numbers: JCOG1904

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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