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JCOG2315: A randomized controlled phase III study comparing local steroid injection alone versus combination therapy of local steroid injection and oral steroid administration for the prevention of esophageal stricture after wide-spreading endoscopic submucosal dissection (E-COMBI)

JCOG2315: A randomized controlled phase III study comparing local steroid injection alone versus combination therapy of local steroid injection and oral steroid administration for the prevention of esophageal stricture after wide-spreading endoscopic submucosal dissection (E-COMBI)

Yano Tomonori

National Cancer Center Hospital East

6-5-1, Kashiwanoha, Kashiwa-shi, Chiba,277-8577 Japan

toyano@east.ncc.go.jp

Kadota Tomohiro

Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East

6-5-1, Kashiwanoha, Kashiwa-shi, Chiba,277-8577 Japan

+81-4-7133-1111

tkadota@east.ncc.go.jp

Recruiting

Dec. 11, 2024

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

prevention purpose

1st inclusion criteria
(1) Meet either of the following.
(a) Histologically proven squamous cell carcinoma, basaloid carcinoma, adenosquamous carcinoma, or adenocarcinoma.
(b) Histologically proven squamous intraepithelial neoplasia and endoscopically diagnosed as esophageal cancer.
(c) No histologically proven esophageal cancer, but endoscopically diagnosed as esophageal cancer.
(2) Major lesion and adjacent sub-lesions located in the cervical esophagus to the esophagogastric junction diagnosed by endoscopy.
(3) The depth of invasion of the major lesion and sub-lesions is diagnosed as cT1a by endoscopy.
(4) Neither lymph node metastases nor distant metastases in neck, chest and abdomen confirmed by contrast-enhanced CT.
(5) Circumferential spread of the major lesion is 2/3 or more, but not entire circumference diagnosed by endoscopy
(6) Length of major lesion is 100 mm or less in longitudinal axis diagnosed by endoscopy.
(7) Circumferential spread is 1/2 or less in all sub-lesions in patients with multiple lesions
(8) Aged >= 18 years old
(9) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
(10) No prior radiotherapy to the neck, chest wall, lung, or mediastinum
(11) No prior surgery for esophagus or mediastinum tumor.
(12) No plan of treatment other than protocol treatment for pharyngolarynx and esophagus within 13 weeks after first registration.
(13) No prior treatment for esophageal cancer unless all of the following are met.
(a) Curative resection (pT1a,Ly0,V0,pVM0) was performed by EMR/ESD.
(b) No stricture after EMR/ESD.
(c) No past EMR/ESD scar contact with major lesion and adjacent sub-lesions.
(14) No history of or concurrent head and neck cancer.
(15) Other malignancies (except esophageal or head and neck cancer) are allowed; however, patients are excluded if:
(a) They received systemic anticancer therapy (excluding endocrine therapy) within 4 weeks before enrollment
(b) Treatment for another malignancy is planned within 24 weeks after the first registration
(16) Dysphagia score >=1.
(17) Sufficient organ function
(a) White blood cell count >=2,000/mm3 and <=12,000/mm3.
(b) Hemoglobin >=8.0 g/dL.
(c) Platelet >=75,000/mm3.
(d) Total bilirubin <=2.0 mg/dL.
(e) Aspartate aminotransferase <=150 U/L.
(f) Alanine aminotransferase <=150 U/L.
(g) Creatinine <=2.0 mg/dL.
(h) HbA1c <7.0%
(18) Written informed consent

2nd inclusion criteria
(1) After first registration in this study.
(2) ESD and local steroid injection have been performed for esophageal cancer and within 6 days from the date of ESD.
(3) En bloc endoscopic resection with no endoscopically evident residual tumor.
(4) Circumferential spread of the post-ESD mucosal defect is more than 7/8 but not entire circumference, and the longitudinal diameter of the post-ESD mucosal defect is 120 mm or less.
(5) Oral steroid administration is possible.
(6) Meet all the following within 1 day.
(a) Body temperature <38.0 degrees Celsius
(b) Infection <=Grade 0

(1) Active infection requiring systemic therapy.
(2) Body temperature >=38.0 degrees Celsius.
(3) Pregnancy, possible pregnancy, within 28 days after delivery or breastfeeding.
(4) Severe psychiatric disease.
(5) Receiving continuous systemic steroid or immunosuppressant treatment.
(6) Uncontrollable diabetes mellitus.
(7) Patients requiring continuous anticoagulant or antiplatelet drug.
(8) Poorly controlled hypertension.
(9) History of unstable angina within 3 weeks or myocardial infarction within 6 months.
(10) Patients with respiratory disease requiring continuous supplemental oxygen.
(11) Active gastroduodenal ulcer.
(12) Glaucoma, posterior capsule opacification or herpetic keratitis, examination by ophthalmologist is not necessarily required.
(13) History of any surgery within 3 months.
(14) Positive HBs antigen.
(15) Allergy to Iodine.
(16) Hypersensitivity for triamcinolone acetonide, prednisolone, trimethoprim-sulfamethoxazole, proton pump inhibitor, and potassium competitive acid blocker.
(17) Glucose-6-phosphate dehydrogenase deficiency.

Both

Widespread superficial esophageal cancer

Local steroid (triamcinolone acetonide or prednisolone) injection to the ulcer immediately after endoscopic submucosal dissection (ESD). Total amount of local steroid injection is 100 mg or 150mg.
Arm A: Observation (local steroid injection alone).
Arm B: Oral steroid (predonisolone) is administered over 8 weeks, started at 30 mg/day and tapered to 20 mg/day by 5 mg per two weeks, and then to 0 mg by 5 mg per week.

Stricture-free survival

The number of endoscopic balloon dilation for 12 weeks after ESD, adverse events, serious adverse events, proportion of patients with dysphagia score =<1 at the time of 12 weeks after ESD, PRO-CTCAE(difficulty swallowing, decreased appetite, nausea, vomiting, heartburn)

+81-4-7133-1111

Oct. 18, 2024

No

none