Clinical trial NCT01740375: Role of Esophagectomy in Complete Responders to CCRT
Official title: A Randomized Phase III Trial on the Role of Esophagectomy in Complete Responders to Preoperative Chemoradiotherapy for Squamous Cell Carcinoma of Esophagus
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Esophageal Squamous Cell Carcinoma
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2012-12-04
Enrollment: 486
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate the role of esophagectomy in complete responders to preoperative chemoradiotherapy for squamous cell carcinoma of esophagus, patients will be randomized to either observation or esophagectomy after concurrent chemoradiotherapy.

Detailed description: After completion of concurrent chemoradiotherapy, patients will be reassed and visited to multidisciplinary clinic, then, randomized to either observation or esophagectomy.

Eligibility criteria: Inclusion Criteria:

1. Histologically proven squamous cell carcinoma of the intrathoracic esophagus
2. Surgically resectable (cT3, cT4a and/or disease with lymph node metastasis by AJCC 7th ed) esophageal cancer, as determined by Endoscopic Ultra Sound (EUS), chest CT and PET-CT
3. No prior treatment for the esophageal cancer
4. Age: 20-70 years
5. ECOG performance status 0, 1 or 2
6. Adequate hematological, renal, hepatic, pulmonary and cardiac functions defined as 6.1 Granulocytes \> 1,500/microliter, Platelets \> 75,000/microliter 6.2 Creatinine \< 1.5 mg/dL (or CCr\> 50 mg/mL), 6.3 Total bilirubin \< 1.5 mg/dL 6.4 ALT and AST \< 2.5 × upper normal limit 6.5 FEV1 \>=1.5 L/min 6.6 Ejection fraction \>= 45%
7. Non-pregnant, non-lactating female patients. Sexually active patients of childbearing potential must implement effective contraceptive practices during the study when treated with chemotherapy
8. Written, voluntary informed consent

Exclusion Criteria:

1. Subtypes other than squamous cell carcinoma
2. cT1N0M0, cT2N0M0 esophageal cancer or in situ carcinoma
3. Invasion of recurrent laryngeal, phrenic or sympathetic nerve
4. Invasion of the tracheobronchial tree or presence of tracheoesophageal fistula
5. Invasion of major vessels (vena cava, azygos vein and aorta) by the tumor
6. Malignant pleural effusion (documented by cytospin or cytology)
7. Cervical esophageal cancer
8. Para-aortic lymph node metastasis
9. Past or current history of malignancy other than entry diagnosis except for non-melanomatous skin cancer, curatively treated carcinoma in situ of the cervix, curatively treated early gastric cancer with endoscopic mucosal resection or a cured malignancy more than 5 years prior to enrollment
10. Previous chemotherapy or prior history of radiotherapy interfering with the planned radiotherapy as per protocol
11. Patients with a known history of HIV seropositivity or HCV (+). Patients with HBV (+) are eligible. However, primary prophylaxis using antiviral agents (i.e. lamivudine, etc) is recommended for HBV carrier to prevent HBV reactivation during whole treatment period.
12. Other serious illness or medical conditions A. Unstable cardiac disease (i.e. congestive heart failure, arrhythmia, symptomatic coronary artery disease) despite treatment, myocardial infarction within 6 months prior to study entry B. History of significant neurologic or psychiatric disorders including dementia or seizures C. Active uncontrolled infection (viral, bacterial or fungal infection) D. Other serious medical illnesses
13. New York heart Association Class III/IV and history of active angina. Documented myocardial infarction within the 6 months preceding registration. Patients with a history of significant ventricular arrhythmia requiring medication or congestive heart failure. History of 2nd or 3rd degree heart blocks.
14. Active infection or other serious underlying medical condition which would impair the ability of the patient to receive the planned treatment
15. Dementia or altered mental status that would prohibit the understanding and giving of informed consent
16. Uncontrolled diabetes mellitus: fasting glucose \>150 mg/dL or patients requiring insulin therapy for glycemic control; fasting glucose \>150 mg/dL or patients requiring insulin therapy for glycemic control;

Primary outcomes:
measure: 2-year disease-free survival (DFS) rate
timeFrame: 2 years from the enrollment of last patient
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: 5 years from the enrollment of last patient
measure: progression-free survival
timeFrame: 5 years from the enrollment of last patient
measure: failure pattern
timeFrame: 5 years from the enrollment of last patient
measure: Number of Participants with Adverse Events
timeFrame: up to 60 days after treatment
measure: Comparison of clinical complete response (cCR) vs. pathologic complete response rate (pCR) in patients who underwent esophagectomy
timeFrame: 5 years
measure: Comparison of OS according to clinical response (CR vs PR vs SD/PD) after preoperative chemoradiotherapy among those who underwent preplanned esophagectomy;
timeFrame: 5 years from the enrollment of the last patient
measure: Comparison of OS according to metabolic response after induction chemotherapy
timeFrame: 5 years from the enrollment of the last patient
measure: Quality of life
timeFrame: 5 years from the enrollment of the last patient
measure: Comparison of PFS according to clinical response (CR vs PR vs SD/PD) after preoperative chemoradiotherapy among those who underwent preplanned esophagectomy;
timeFrame: 5 years from the enrollment of the last patient
measure: Comparison of TTF according to clinical response (CR vs PR vs SD/PD) after preoperative chemoradiotherapy among those who underwent preplanned esophagectomy;
timeFrame: 5 years from the enrollment of the last patient
measure: Comparison of PFS according to metabolic response after induction chemotherapy
timeFrame: 5 years from the enrollment of the last patient
measure: Comparison of TTF according to metabolic response after induction chemotherapy
timeFrame: 5 years from the enrollment of the last patient
measure: treatment-related mortality
timeFrame: up to 60 days after completion of treatment
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
Study officials:
affiliation: Asan Medical Center
name: Sung-Bae Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: