The Efficacy of Neoadjuvant Chemoradiotherapy in Comparison With Neoadjuvant Chemotherapy in Patients With Resectable Squamous Cell Esophageal Cancer
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, feasibility and outcomes of neoadjuvant chemotherapy followed by esophagectomy versus neoadjuvant chemoradiotherapy followed by esophagectomy for locally advanced resectable esophageal squamous cell carcinoma cT3-4aN0M0, cT1-4aN1-3M0. This is non-inferiority study (neoadjuvant chemoradiotherapy has no advantage over neoadjuvant chemotherapy).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
It is a prospective open-label randomized phase III clinical trial sponsored by N.N. Blokhin NMRC of Oncology. 156 patients with locally advanced resectable esophageal squamous cell carcinoma (cT3-4aN0M0, cT1-4aN1-3M0) are recruited and randomly assigned into the neoadjuvant chemoradiotherapy group (nCRT) followed by esophagectomy and the neoadjuvant chemotherapy group (nCT) followed by esophagectomy according to the proportion of 1:1. The safety, efficacy of protocols and prognosis of patients are compared between the two regimens.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Neoadjuvant Chemoradiotherapy Carboplatin (AUC 2 mg/mL per min) and Paclitaxel (50 mg/m2 of body-surface area) were administered intravenously for five cycles, starting on days 1, 8, 15, 22, and 29. A total radiation dose of 41,4 Gy was given in 23 fractions of 1,8 Gy, 5 days per week. After neoadjuvant therapy, patients receive Ivor-Lewis or Mckeown Esophagectomy. |
Procedure: Patients undergoing neoadjuvant chemoradiotherapy plus Ivory-Lewis or McKeown esophagectomy.
Patients undergoing neoadjuvant chemoradiotherapy plus Ivory-Lewis or McKeown esophagectomy.
|
| Experimental: Neoadjuvant Chemotherapy 4 cycles of DCF regimen (docetaxel 75 mg/m2 day, CDDP 75 mg/m2 and 5FU at 750 mg/m2/ day for 5 days) every 3 weeks. Patients with dysphagia 3 оr with weight loss more then 10% 6 cycles of modified-DCF regimen will be performed (mDCF, docetaxel 50 mg/m2 day, CDDP 50 mg/m2 day and 5-FU at 2400 mg/m2/day for 2 days) every 3 weeks. After neoadjuvant therapy, patients receive Ivor-Lewis or Mckeown Esophagectomy. |
Procedure: Patients undergoing neoadjuvant chemotherapy plus Ivory-Lewis or McKeown esophagectomy
Patients undergoing neoadjuvant chemotherapy plus Ivory-Lewis or McKeown esophagectomy
|
Outcome Measures
Primary Outcome Measures
- Disease-free survival [3(5) years after last patient enrolled]
Survival without local or systemic recurrence
Secondary Outcome Measures
- Overall survival [3(5) years after last patient enrolled]
Overall survival of patients
- Treatment related complications [During the procedure]
Сomplications after treatment
- Number of cycles, frequency of neoadjuvant therapy reduction [During the procedure]
Number of chemotherapy/chemoradiotherapy cycles and doses and dose reductions
- Correlation between genetic profile and tumor response [Immediately after the procedure]
Influence of the genetic profile on the tumor response
- Pathological response rate(pCR) [Immediately after the surgery]
Frequency of pathological pathomorphosis
- R0 resection rate [Immediately after the surgery]
Residual tumor rate
Eligibility Criteria
Criteria
Inclusion Criteria:
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Written informed consent.
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Histologically confirmed squamous cell carcinoma of the esophagus.
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Clinical stage cT1-4aN1-3M0 (AJCC/UICC 8th Edition).
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Indications for surgical esophageal resection
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ECOG status 0-1.
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Adequate bone marrow function (White Blood Cells > 3.0 x 109/L; Neutrophil > 2.0 × 109/L; Hemoglobin > 90 g/L; Platelets > 100 x 109/L).
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Adequate liver function (Total bilirubin < 1.5 x Upper Level of Normal (ULN); Aspartate transaminase (AST) and Alanine transaminase (ALT) < 3.0 x ULN);
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Adequate renal function (Glomerular filtration rate (CCr) > 50 ml/min.
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Adequate cardiac function. Left ventricular ejection fraction > 50%.
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Age from 18 years to 70
Exclusion Criteria:
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Clinical stage cT4bcN0cM0 (AJCC/UICC 8th Edition).
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Patients with advanced non-operable or metastatic esophageal cancer.
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Patients who have received or are receiving other chemotherapy, radiotherapy or targeted therapy.
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Patients with another previous or current malignant disease.
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Allergy or contraindications to Paclitaxel, Carboplatin, Docetaxel, Cisplatin or Fluoruracil.
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Patients with active infection of immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV); HIV seropositivity; HBV DNA or HCV RNA positive.
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Severe concomitant diseases (uncontrolled arterial hypertension, diabetes mellitus, stroke less than 6 months old, mental disorders, other tumors, etc.).
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Clinically significant coronary artery disease (NYHA III / IV), congestive heart failure (NYHAIII / IV), clinically significant cardiomyopathy, myocardial infarction within the last 6 months, or high risk of uncontrolled arrhythmia.
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Chronic inflammatory diseases of the gastrointestinal tract
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Acute infectious diseases.
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Pregnancy or breast feeding.
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Serious concomitant physical and mental illness / abnormalities or territorial reasons that may prevent the patient from participating in the protocol and adherence to the protocol schedule.
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Foreigners or persons with limited legal rights.
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Any medical, geographic, or social circumstance, that in the opinion of the investigator excludes the patient's participation in the protocol.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | N.N. Blokhin National Medical Research Center of Oncology | Moscow | Russian Federation | 115478 |
Sponsors and Collaborators
- Blokhin's Russian Cancer Research Center
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ENCHENEC