This clinical trial has two stages: phase II and phase III. Eligible patients will be randomized 1:1 to the two arms: paclitaxel plus cisplatin and cisplatin plus 5-fluorouracil. The phase II stage will enroll 128 patients, 64 patients for each arm. The endpoint of the phase II stage is complete pathological response (pCR). If the endpoint, i.e., the significant improvement of pCR rate, is met, the clinical trial will proceed to the phase III stage, in which 120 more patients will be enrolled. The estimated enrollment time is four years with 3 more years of follow-up after completing enrollment. The primary endpoint of the clinical trial is overall survival, and the secondary endpoints include clinical response, disease free survival, operation rate, complete resection rate, tumor regression rate, hospital stay days after surgery, safety and toxicity, and quality of life.
Stage 1: Neoadjuvant chemoradiation (CRT): Stage 2: Evaluation of clinical responses 1. Evaluation will be done at 3±1 weeks after completing the last fraction of radiotherapy. 2. Evaluation will be performed with panendoscopy, endoscopic ultrasonography (EUS), computed tomography (CT), and positron emission tomography (PET). Stage 3: Surgery 1. Patients will receive esophagectomy with two field lymph node dissection unless: A. Patients become medically unfit for surgery. B. Tumor becomes metastatic or unresectable. C. Patients refuse surgery. 2. Patients who do not receive surgery will go on a second section of CRT: A. Radiation: 180cGy/fraction, once daily, 5 days a week, up to a total of 6,300cGy. B. Arm A: i. T: Paclitaxel 50 mg/m2, 1h IVF, weekly, week 1 to week 3 during CRT. ii. P: Cisplatin 30 mg/m2, 2 h IVF, weekly following paclitaxel, week 1 to week 3 during CRT. C. Arm B: i. P: Cisplatin 75 mg/m2, 2 h IVF, on day 1 of week 1 during CRT. ii. F: 5-FU 1,000 mg/m2, 24 h IVF, on day 1, 2, 3, 4 of week 1 during CRT. 3. Patients, who receive surgery with R2 resection or the pathology showing positive margins or extracapsular invasion of regional lymph nodes, will also receive the second section of CRT described in above-mentioned stage 3-2.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
248
Neoadjuvant chemoradiation: 1. Radiation: 180cGy/fraction, once daily, 5 days a week, to a total of 4,500cGy. 2. Chemotherapy: Arm A or Arm B Surgery: esophagectomy and 3-fields lymph node dissection
National Taiwan University Hospital
Taipei, Taiwan
RECRUITINGpathological complete response
No cancer cells in primary tumor and all lymph nodes resected are observed by pathologists
Time frame: 2 years
Overall survival
Time from enrollment to death
Time frame: 4 years
disease free survival
From the day of surgery with R0 resection to recurrence or death of any reasons
Time frame: 4 years
clinical response
The clinical response evaluation for the effect of neoadjuvant CRT will be done around 3±1 weeks after completing CRT. Evaluation will be performed with panendoscopy, EUS, CT, and PET. Clinical responses assessment will include: 1. Overall clinical response according to RECIST1.1 and Japanese Esophageal Society (JES) 2. Endoscopic response criteria according to JES 3. Metabolic response evaluated by PET
Time frame: 2 years
operation rate
The ratio of the number of patients who receive surgery over the number of patients enrolled
Time frame: 2 years
R0 resection rate
The ratio of the number of patients with surgical R0 resection over the number of patients who receive surgery
Time frame: 2 years
tumor regression grade
A 4-tiered tumor regression grading (TRG) system will be used according to the extent of residual carcinoma in the whole tumor area of the esophageal specimen. TRG 1: no residual carcinoma. TRG 2: 1%- 10% residual carcinoma. TRG 3: 11%- 50% residual carcinoma. TRG 4: \>50% residual carcinoma
Time frame: 2 years
The total score of participants of both arms will be analyzed and compared.
By World Health Organization Quality of Life Brief Version (WHOQOL-BREF) Taiwan version (2005), quality of life will be assessed at enrollment, at the end of neoadjuvant CRT, and 3 months after surgery. There are 28 subscales in the questionnaire. Each subscale has 5 scores from 1 (the worst) to 5 (the best). The scores of each subscale are summed to be a total score.
Time frame: 2 years
Number of participants with treatment-related adverse events as assessed by the NCI Common Toxicity Criteria (CTC)
By the NCI Common Toxicity Criteria (CTC), version 4.0., number of participants with treatment-related adverse events, all grades and grade 3/4, will be assessed.
Time frame: 2 years
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