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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Esophageal Cancer
• Intervention / Treatment: Drug: 5-fluorouracil; Drug: Cisplatin; Radiation: Radiation therapy; Procedure: Esophagectomy

Detailed 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

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Korea, Republic of
  • Goyang-si, Korea, Republic of
    • National Cancer Center
  • Pusan, Korea, Republic of, 06351
    • Pusan National University Hospital
  • Seongnam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Gangnam Severance Hospital
  • Seoul, Korea, Republic of
    • Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of
    • Korea University Guro Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Concurrent Chemoradiotherapy; Patients receive 2 courses (every 3 weeks) of chemotherapy including cisplatin (45-60mg/m2) intravenously over 1 hour on day 1 and 5-fluorouracil (3,200 ~ 4,000mg/m2) intravenously for 4 to 5 days. Patients receive a total of 45 Gy radiation therapy (5 days a week for 5 weeks).	Drug: 5-fluorouracil; 3,200 ~ 4,000mg/m2 intravenously for 4 to 5 days.; Other Names: 5-FU; Drug: Cisplatin; 45~60mg intravenously over 1 hour on day 1; Radiation: Radiation therapy; 45 Gy irradiation (5 days a week for 5 weeks)
Active Comparator: Esophagectomy; Patients receive surgical resection, including Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy.	Procedure: Esophagectomy; Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Collaborators: Ministry of Health & Welfare, Korea
• Investigators: Principal Investigator: Hong Kwan Kim, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2017
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: September 30, 2017
• First Submitted That Met QC Criteria: October 5, 2017
• First Posted (Actual): October 11, 2017

Study Record Updates

• Last Update Posted (Actual): May 23, 2024
• Last Update Submitted That Met QC Criteria: May 22, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Neoplasms, Squamous Cell; Esophageal Neoplasms; Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Fluorouracil
• Other Study ID Numbers: 2017-04-074

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No