Cetuximab/Paclitaxel/Cisplatin Concurrent Chemoradiotherapy Followed by Esophagectomy for Loco-regional Esophageal Cancer

Study Overview
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Brief Summary
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We hypothesize that the addition of cetuximab to twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy (TP-CCRT) as the adjunctive therapy before esophagectomy or as a definitive CRT would improve the therapeutic efficacy of TP-CCRT in patients with loco-regional esophageal squamous cell carcinoma (ESCC).

Detailed Description
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We hypothesize that the addition of cetuximab to twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy as the adjunctive therapy before esophagectomy or as a definitive CRT would improve the therapeutic efficacy of TP-CCRT in patients with loco-regional esophageal squamous cell carcinoma.

Official Title
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A Phase II Study of Combining Cetuximab Plus Twice Weekly Paclitaxel/Cisplatin Concurrent Chemoradiotherapy (TP-CCRT) Followed With or Without Esophagectomy for Loco-regional Esophageal Squamous Cell Carcinoma (ESCC)

Conditions
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Esophageal Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Paclitaxel
* Drug: Cisplatin
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically proven squamous cell carcinoma of esophagus. Loco-regional diseases, which are defined by TNM system of American Joint Committee on Cancer (AJCC) Cancer Staging System (6th edition) in 2002, fulfilling one of the following criteria: A. T3, N0, M0; B. T1-3, N1, M0; C. T1-3 or N0-1, M1a will be eligible provided the lesions could be covered by appropriate radiation fields. Age ≥ 18 years old. Performance status ECOG 0 2. Adequate bone marrow reserves, defined as: A. white blood cells (WBC) ≥ 4,000/µl or neutrophil count (ANC) ≥ 2,000/µl; B. platelets ≥ 100,000/µl. Adequate liver function reserves, defined as: A. hepatic transaminases ≤ 2.5 x upper limit of normal (ULN); B. serum total bilirubin ≤ 1.5 x upper limit of normal (ULN). Adequate renal function: Creatinine ≤1.5 mg/dl Written informed consent. Exclusion Criteria: Invasion to surrounding organ (T4 disease). Distant metastasis, except M1a disease listed in the inclusion criteria 2-C. Adenocarcinoma of gastroesophageal (GE) junction. Prior thoracic irradiation. Synchronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer. Prior malignancy, except for the following: A. adequately treated basal cell or squamous cell skin cancer; B. in-situ cervical cancer; C. Note: previously treated aerodigestive squamous cell carcinoma is not allowed. Significant co-morbid disease, which prohibit the conduction of chemotherapy, concurrent chemoradiotherapy, or radical surgery, such as active systemic infection, symptomatic cardiac or pulmonary disease, or psychiatric disorders. Estimated life expectancy less than 3 months.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Targeted therapy<br>Concurrent chemoradiotherapy with cetuximab, paclitaxel, and cisplatin followed by, if feasible, esophagectomy | Drug: Cetuximab<br>* Cetuximab: loading dose 400 mg/m2, 2h- IVF, 3  5 days prior to starting CCRT (on week-1); followed by 250 mg/m2/ week, 1h- IVF, for 4 weeks (i.e., week 1 to week 4. during CCRT).<br>* Other names: Erbitux;Drug: Paclitaxel<br>* T: Paclitaxel 35 mg/m2, 1h IVF, on day 1 and day 4 of each week, week1 to week4 during CCRT.<br>Drug: Cisplatin<br>* P: Cisplatin 15 mg/m2, 1 h IVF, on day 2 and day 5 of each week, week1 to week4 during CCRT.<br>Radiation: Radiotherapy<br>* Radiotherapy: (three-dimensional conformal radiotherapy or intensity modulated radiotherapy) 200 cGy/fraction, once daily, 5 days a week, to a total dose of 4000 cGy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the clinical response rate in patients with loco-regional esophageal squamous cell carcinoma treated with cetuximab combined with twice weekly paclitaxel/cisplatin concurrent chemoradiotherapy (C-TP-CCRT, 40 Gy). |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic complete response (pCR). |  | 2 years | 
| Disease-free survival. |  | 2 years | 
| Safety and toxicity of cetuximab combined with twice weekly TP-CCRT, followed by surgery. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Esophageal cancer, Chemoradiotherapy, Paclitaxel, Cetuximab