Neoadjuvant Chemotherapy Followed by Preoperative Chemoradiation in Resectable Squamous-cell Esophageal Cancer

Study Overview
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Brief Summary
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This study is conducted to evaluate efficacy and safety of neoadjuvant chemotherapy followed by preoperative chemoradiotherapy in patients with resectable esophageal squamous cell carcinoma

Detailed Description
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This study is conducted to evaluate efficacy and safety of neoadjuvant chemotherapy followed by preoperative chemoradiotherapy in patients with resectable esophageal squamous cell carcinoma. Patients with resectable esophageal squamous cell carcinoma receive 2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). Patients who do not progress with distant metastases start preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gy for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy irrespectively of objective response.

Official Title
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Neoadjuvant Chemotherapy Followed by Preoperative Chemoradiation in Resectable Squamous-cell Esophageal Cancer: Single Arm Phase II Study

Conditions
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Esophageal Neoplasms, Squamous Cell Carcinoma, Concurrent Chemoradiotherapy

Intervention / Treatment
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* Drug: Paclitaxel
* Drug: Cisplatin
* Drug: Fluorouracil
* Radiation: chemoradiotherapy
* Procedure: Ivor Lewis esophagogastrectomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 18-75 Histologically or cytologically confirmed resectable squamous-cell Tumor (T)1-2 node (N)+, T3N0-3 esophageal cancer. Inclusion of patients with morphologically confirmed and potentially resectable supraclavicular lymphnodes (unilateral, less than 1,5 cm in short axis) is allowed No prior antineoplastic treatment Eastern Cooperative Oncology Group (ECOG) status 0-2 Adequate organ function, evidenced by laboratory results with no contraindications to chemotherapy absolute neutrophil count ≥ 1,500 х109/l thrombocytes ≥ 100 х 109/l hemoglobin ≥ 90 mg/l creatinine < 115 µmol/л or creatinine clearance ≥ 55 ml/min alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 x upper limit of normal (ULN) alkaline phosphatase (ALP) > 5 x ULN bilirubin > 1,5 х ULN Women of childbearing potential must have negative pregnancy test, performed 7 days prior to initial treatment Patients must follow appropriate contraception rules during whole treatment period Decrease of body weight must not be more than 20% in last 6 months Exclusion Criteria: Presence of distant metastases except for metastatic supraclavicular lymphnodes; Bulky (>3 cm) regional lymphnodes metastases; Cervical esophageal cancer; Presence of tumor fistula; Prior malignant tumor, except for proper treated skin basal cell carcinoma and in situ cervical cancer; Active infectious diseases and concomitant diseases that can affect treatment tolerability, surgery and other study procedures;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trimodality approach<br>2 cycles of neoadjuvant chemotherapy (paclitaxel 175 mg/м2 iv day 1, cisplatin 75 mg/м2 iv day 1, fluorouracil 750 mg/m2/day continuous infusion, day 1-4 every 3 weeks). 3-4 weeks later - preoperative chemoradiotherapy (paclitaxel 50 mg/m2 + cisplatin 20 mg/m2 weekly + radiotherapy 44 Gray (Gy) for 4 weeks). 4-6 weeks after completion of chemoradiation patients undergo Ivor Lewis esophagogastrectomy. | Drug: Paclitaxel<br>* Paclitaxel is used in two cycles of neoadjuvant chemotherapy and concomitant chemoradiotherapy<br>* Other names: chemotherapy;Drug: Cisplatin<br>* Cisplatin is used in two cycles of neoadjuvant chemotherapy and concomitant chemoradiotherapy<br>* Other names: chemotherapy;Drug: Fluorouracil<br>* Fluorouracil is used in two cycles of neoadjuvant chemotherapy<br>* Other names: chemotherapy;Radiation: chemoradiotherapy<br>* Distant 3D radiotherapy, single dose 2 Gray (Gy), total dose 44Gy.<br>* Other names: chemoradiation;Procedure: Ivor Lewis esophagogastrectomy<br>* Open Ivor Lewis esophagogastrectomy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Disease free survival will be calculated from the start of the treatment to the disease progression or death of any reason. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival will be calculated from the start of the treatment to the death of any reason. | 24 months | 
| Objective response rate according to RECIST 1.1 | Objective response rate will be evaluated separately after chemotherapy and chemoradiotherapy. | 24 months | 
| Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Toxicity will be assessed separately after chemotherapy, chemoradiotherapy and surgery according NCI CTC AE 4.0 | 24 months | 
| Pathological complete response rate following chemoradiotherapy | Pathological complete response rate following chemoradiotherapy will be assessed in resected patients | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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esophageal squamous cell carcinoma, preoperative chemoradiotherapy, preoperative chemotherapy