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

NCT03306901 | Active Not Recruiting

• 1 other identifier: 2017-04-074
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 9

Brief 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.

Conditions

Esophageal Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Overall survival

  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

  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)

  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)

  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)

  Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)

Study Arms (2)

Concurrent Chemoradiotherapy

EXPERIMENTAL

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; Drug: Cisplatin; Radiation: Radiation therapy

Esophagectomy

ACTIVE COMPARATOR

Patients receive surgical resection, including Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy.

Procedure: Esophagectomy

Interventions

Esophagectomy PROCEDURE

Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy

Esophagectomy

5-fluorouracil DRUG

3,200 \~ 4,000mg/m2 intravenously for 4 to 5 days.

Also known as: 5-FU

Concurrent Chemoradiotherapy

Cisplatin DRUG

45\~60mg intravenously over 1 hour on day 1

Concurrent Chemoradiotherapy

Radiation therapy RADIATION

45 Gy irradiation (5 days a week for 5 weeks)

Concurrent Chemoradiotherapy

Eligibility Criteria

• Age: 19 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 19 years and \< 80 years
• Histologically confirmed squamous cell carcinoma of the esophagus
• Clinical stage as cT1N0M0 (AJCC/UICC 7th Edition) according to upper GI endoscopy or endoscopic ultrasound and chest computed tomography (CT) scans
• Pathologic examination after endoscopic submucosal dissection confirmed the presence of submucosal invasion (pathologic T1b) or lymphovascular invasion
• 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
• Participants has adequate hematologic function, as evidenced by an absolute neutrophil count (ANC) ≥1000/µL, hemoglobin ≥8 g/dL, and platelets ≥85,000/µL
• 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
• Participants should agree to participate in the study and sign the informed consent form

You may not qualify if:

• Cervical esophageal cancer (proximal to 20cm from incisor teeth)
• 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))
• Recurrent esophageal cancer
• 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
• Gastric conduit is not available for esophageal reconstruction (ex.: previous history of gastrectomy)

Sponsors & Collaborators

• Samsung Medical Center: lead
• Ministry of Health & Welfare, Korea: collaborator

Study Sites (9)

National Cancer Center

Goyang-si, South Korea

Location

Pusan National University Hospital

Pusan, 06351, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Seoul St. Mary's Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Esophageal Neoplasms

Interventions

Esophagectomy; Fluorouracil; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Digestive System Surgical Procedures; Surgical Procedures, Operative; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Study Officials

• Hong Kwan Kim, MD, PhD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors and data analysists will be blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief of Department of General Thoracic Surgery

Study Record Dates

• First Submitted: September 30, 2017
• First Posted: October 11, 2017
• Study Start: October 20, 2017
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2033
• Last Updated: May 23, 2024

Record last verified: 2024-05

Locations

KR (9)