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

• Sponsor: Samsung Medical Center (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03306901
• Collaborator: Ministry of Health & Welfare, Korea (Other)
• Enrollment: 240
• Locations: 9
• Arms: 2
• Anticipated Duration (Months): 134.4
• Patients Per Site: 26.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Esophageal Cancer	Procedure: Esophagectomy; Drug: 5-fluorouracil; Drug: Cisplatin; Radiation: Radiation therapy	N/A

Detailed Description

• Compare 3-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 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 Design

• Study Type: Interventional
• Anticipated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Outcome assessors and data analysists will be blinded
• Primary Purpose: Treatment
• Official Title: A Randomized Multicenter Noninferiority Trial Comparing Chemoradiotherapy Versus Esophagectomy After Endoscopic Submucosal Dissection for Superficial Esophageal Squamous Cell Carcinoma (ASSURE)
• Actual Study Start Date: Oct 20, 2017
• Anticipated Primary Completion Date: Dec 31, 2023
• Anticipated Study Completion Date: Dec 31, 2028

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 3-year overall survival [3 years from the randomization (will be assessed up to 36 months)]

   defined as the time from randomization to the date of death from any cause or the last follow-up

Secondary Outcome Measures

1. Overall survival [1 year, 2 years, 5 years from the randomization (will be assessed up to 60 months)]

   defined as the time from randomization to the date of death from any cause or the last follow-up

2. Disease-free survival [1 year, 2 years, 3 years, 5 years from the randomization (will be assessed up to 60 months)]

   defined as the time from randomization to the first recurrence or the date of death from any cause or the last follow-up

3. 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)]

   assessed by EORTC QLQ C-30

4. 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)]

   assessed by EORTC QLQ EOS-18

5. 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)]

   assessed by GSRS

6. Quality of life (Depression) [Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)]

   assessed by PHQ-9

7. Quality of life (Sleep disorder) [Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)]

   assessed by PSQI

8. Quality of life (Fatigue) [Baseline, 3 months, 6 months, 1 year, 2 years, 3 years from treatment (will be assessed up to 36 months)]

   assessed by BFI

9. Treatment-related complications or adverse events [from treatment to the date of death from any cause or last follow-up (will be assessed up to 60 months)]

   assessed by NCI CTCAE ver 4.0

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Cancer Center	Goyang-si		Korea, Republic of
2	Pusan National University Hospital	Pusan		Korea, Republic of	06351
3	Seoul National University Bundang Hospital	Seongnam		Korea, Republic of
4	Asan Medical Center	Seoul		Korea, Republic of
5	Gangnam Severance Hospital	Seoul		Korea, Republic of
6	Korea University Guro Hospital	Seoul		Korea, Republic of
7	Samsung Medical Center	Seoul		Korea, Republic of
8	Seoul National University Hospital	Seoul		Korea, Republic of
9	Seoul St. Mary's Hospital	Seoul		Korea, Republic of

Sponsors and Collaborators

• Samsung Medical Center
• Ministry of Health & Welfare, Korea

Investigators

• Principal Investigator: Hong Kwan Kim, MD, PhD, Samsung Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Hong Kwan Kim, Chief of Department of General Thoracic Surgery, Samsung Medical Center
• ClinicalTrials.gov Identifier: NCT03306901
• Other Study ID Numbers: 2017-04-074
• First Posted: Oct 11, 2017
• Last Update Posted: May 9, 2022
• Last Verified: May 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma, Squamous Cell; Esophageal Squamous Cell Carcinoma; Fluorouracil

Study Results

No Results Posted as of May 9, 2022