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

NCT ID: NCT03306901

Last Updated: 2024-05-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 240 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-20
• Study Completion Date: 2033-12-31

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.

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

Conditions

Esophageal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

5-fluorouracil

Intervention Type: DRUG

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

Cisplatin

Intervention Type: DRUG

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

Radiation therapy

Intervention Type: RADIATION

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

Esophagectomy

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

Group Type: ACTIVE_COMPARATOR

Esophagectomy

Intervention Type: PROCEDURE

Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy

Interventions

Esophagectomy

Ivor Lewis esophagectomy or McKeown esophagectomy and systematic lymphadenectomy

Intervention Type: PROCEDURE

5-fluorouracil

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

Intervention Type: DRUG

Cisplatin

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

Intervention Type: DRUG

Radiation therapy

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

Intervention Type: RADIATION

Other Intervention Names

5-FU

Eligibility Criteria

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)

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Health & Welfare, Korea

OTHER_GOV

Sponsor Role: collaborator

Samsung Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Hong Kwan Kim

Chief of Department of General Thoracic Surgery

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hong Kwan Kim, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Samsung Medical Center

Locations

National Cancer Center

Goyang-si, , South Korea

Pusan National University Hospital

Pusan, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Asan Medical Center

Seoul, , South Korea

Gangnam Severance Hospital

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Seoul St. Mary's Hospital

Seoul, , South Korea

Countries

South Korea

Other Identifiers

2017-04-074

Identifier Type: -

Identifier Source: org_study_id