Chemoradiotherapy Versus Esophagectomy After Endoscopic Resection for Superficial Esophageal Squamous Cell Carcinoma

Esophageal Cancer Clinical Trial

— ASSURE  

Official title:

A Randomized Multicenter Noninferiority Trial Comparing Chemoradiotherapy Versus Esophagectomy After Endoscopic Submucosal Dissection for Superficial Esophageal Squamous Cell Carcinoma (ASSURE)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03306901
• Other study ID #: 2017-04-074
• Status: Active, not recruiting
• Phase: N/A
• Start date: October 20, 2017
• Est. completion date: December 31, 2033

Study information

• Verified date: May 2024
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a randomized noninferiority multicenter trial. Patients will be stratified according to the participating hospital. Patients will be randomized to one of the treatment arms.

Arm A: Patients will receive surgical resection, including Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy.

Arm B: Patients will receive 5-fluorouracil (5-FU) and cisplatin-based chemotherapy concurrently with radiotherapy. Patients will receive cisplatin (45~60mg/m2) intravenously over 1 hour on day 1 and receive 5-FU (3,200 ~ 4,000mg/m2) intravenously for 4 to 5 days. Treatment will repeat every 3 weeks for 2 courses. Patients will receive a total of 45 Gy irradiation (5 days a week for 5 weeks).

Patients will be followed at 3 and 6 months after randomization, then every 6 months for following 2 and half years (up to 3 years after randomization), and 4 and 5 years after randomization. After 5 years, annual follow-up is scheduled up to 10 years after randomization.

We will analyze the results primarily with the intention-to-treatment(ITT) analysis, and then secondarily with the per-protocol(PP) analysis as well.

Description:

• Compare 1-year, 2-year, 3-year, 5-year, 6-year, 7-year, 8-year, 9-year, 10-year overall survival between concurrent chemoradiotherapy and esophagectomy among patients who require additional treatment for esophageal squamous cell carcinoma endoscopically resected but found to have pT1b (submucosal invasion) or lymphovascular invasion

• Compare 1-year, 2-year, 3-year, 5-year, 6-year, 7-year, 8-year, 9-year, 10-year disease-free survival between concurrent chemoradiotherapy and esophagectomy in the same study population

• Compare quality of life between concurrent chemoradiotherapy and esophagectomy in the same study population

• Compare treatment-related adverse event between concurrent chemoradiotherapy and esophagectomy in the same study population

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: December 31, 2033
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years to 79 Years

Eligibility

Inclusion Criteria:

1. Age = 19 years and < 80 years

2. Histologically confirmed squamous cell carcinoma of the esophagus

3. Clinical stage as cT1N0M0 (AJCC/UICC 7th Edition) according to upper GI endoscopy or endoscopic ultrasound and chest computed tomography (CT) scans

4. Pathologic examination after endoscopic submucosal dissection confirmed the presence of submucosal invasion (pathologic T1b) or lymphovascular invasion

5. For participants with multiple lesions, all of them should be resected with endoscopic submucosal dissection and at least one lesion should have pathologic submucosal invasion (pT1b) or lymphovascular invasion

6. Participants has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) =1000/µL, hemoglobin =8 g/dL, and platelets =85,000/µL

7. Participants has adequate hepatic and renal function as defined by aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 times the upper limit of normal ; a total bilirubin =1.5 times the upper limit of normal ; creatinine clearance = 30mL/min/1.73m2

8. Participants should agree to participate in the study and sign the informed consent form

Exclusion Criteria:

1. Cervical esophageal cancer (proximal to 20cm from incisor teeth)

2. Regional lymph node metastasis (cN+) or distant metastasis (cM1) are suspected or confirmed on chest CT scans or positron emission tomography (PET)/CT scans (Equivocal results will be regarded as no metastasis. However, it can also perform a biopsy if necessary (optional))

3. Recurrent esophageal cancer

4. Uncontrolled systemic disease which makes participants medically unfit for additional treatment (esophagectomy or concurrent chemoradiotherapy) such as congestive heart failure, interstitial lung disease, severe pulmonary emphysema or chronic renal failure

5. Gastric conduit is not available for esophageal reconstruction (ex.: previous history of gastrectomy)

6. Synchronous or metachronous multiple cancers (within the past 3 years) with the exclusion of skin cancer, well differentiated thyroid cancer, carcinoma in situ, early cancer achieving curative endoscopic resection, or low grade prostate cancer (Gleason Score=6)

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Esophageal Cancer
• Esophageal Squamous Cell Carcinoma

Intervention

Procedure:
• Esophagectomy
Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy

Drug:
• 5-fluorouracil
3,200 ~ 4,000mg/m2 intravenously for 4 to 5 days.
• Cisplatin
45~60mg intravenously over 1 hour on day 1

Radiation:
• Radiation therapy
45 Gy irradiation (5 days a week for 5 weeks)

Locations

Country	Name	City	State
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Pusan National University Hospital	Pusan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Gangnam Severance Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Samsung Medical Center	Ministry of Health & Welfare, Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	3-year overall survival	defined as the time from randomization to the date of death from any cause or the last follow-up	3 years from the randomization (will be assessed up to 36 months)
Secondary	Overall survival	defined as the time from randomization to the date of death from any cause or the last follow-up	1 year, 2 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years from the randomization (will be assessed up to 60 months)
Secondary	Disease-free survival	defined as the time from randomization to the first recurrence or the date of death from any cause or the last follow-up	1 year, 2 years, 3 years, 4 years, 5 years, 6 years, 7 years, 8 years, 9 years, 10 years from the randomization (will be assessed up to 60 months)
Secondary	Quality of life (Cancer patient-specific)	assessed by EORTC QLQ C-30	Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)
Secondary	Quality of life (Esophageal cancer-specific symptom)	assessed by EORTC QLQ EOS-18	Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)
Secondary	Quality of life (Gastrointestinal symptom)	assessed by GSRS	Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)
Secondary	Quality of life (Depression)	assessed by PHQ-9	Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)
Secondary	Quality of life (Sleep disorder)	assessed by PSQI	Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)
Secondary	Quality of life (Fatigue)	assessed by BFI	Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)
Secondary	Treatment-related complications or adverse events	assessed by NCI CTCAE ver 4.0	from treatment to the date of death from any cause or last follow-up (will be assessed up to 60 months)