Neoadjuvant Erbitux Based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer

Study Overview
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Brief Summary
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EGFR is a potential target for new anticancer therapy in head and neck squamous cell carcinoma, because blocking the EGFR by a monoclonal antibody results in inhibition of the stimulation of the receptor, therefore, in inhibition of cell proliferation, enhanced apoptosis, and reduced angiogenesis, invasiveness and metastases. The study hypothesis is that neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy for locally advanced oral/oropharyngeal cancer could benefit the patients on prognosis. The endpoints of this study are the pathological complete response after neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy, the survival rate, and the safety.

Detailed Description
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The primary endpoint of this study is the pathological complete response after neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy. The second endpoint of this study is the disease free survival rates (1, 2, 3, 5 years), locoregional control rates (1, 3, 5 years), overall survival rate (3, 5 years), and the safety.

Official Title
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Neoadjuvant Erbitux Based Chemotherapy for Locally Advanced Oral/Oropharyngeal Cancer

Conditions
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Locally Advanced Malignant Neoplasm, Oral Cancer, Oropharyngeal Carcinoma, Effects of Chemotherapy

Intervention / Treatment
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* Drug: Neo-adjuvant Erbitux-based chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to any study activities Age 18-75 Histological/cytological and iconography confirmed squamous-celled oral/oropharyngeal cancer Stage Ⅲ/Ⅳa (T1-2, N1-2, M0 or T3-4, N0-2, M0, AJCC 2010), operable disease Karnofsky performance status (KPS) ≥70 Adequate hematologic function: Neutrophils ≥1,500/mm^3, WBC >4,000/mm^3, Hb > 10 g/dL, platelet count >100,000/mm^3 Hepatic function: ALAT/ASAT <2.5 times the upper limit of normal (ULN), bilirubin <1.5 x ULN Renal function: serum creatinine <1.5 x ULN Life expectancy ≥6 months Exclusion Criteria: Evidence of distant metastatic disease and other oropharyngeal cancers Surgical procedure of the primary tumor or lymph nodes (except diagnostic biopsy) before study treatment Previous radiotherapy for the primary tumor or lymph nodes Previous exposure to epidermal growth factor-targeted therapy Prior chemotherapy or immunotherapy for the primary tumor Other previous malignancy within 5 years, except non-melanoma skin cancer or pre-invasive carcinoma of the cervix Any investigational agent prior to the 1st study medication Participation in another clinical study within the 30 days prior to Inclusion in this study. Peripheral neuropathy >grade 1 Known grade 3 or 4 allergic reaction to any of the study treatment History of severe pulmonary or cardiac disease Creatinine Clearance <30 ml/min Know drug abuse /alcohol abuse Legal incapacity or limited legal capacity Active systemic infection Medical or psychiatric illness, which in the investigators' opinions, would not permit the subject to complete or fully and completely understand the risks and potential complications of the study Concurrent chronic systemic immune therapy or hormone therapy not indicated in the study protocol Pregnancy (confirmed by serum or urine β-HCG) or lactation period Severe cardiac disease such as heart failure, clinical relevant cardiac dysrhythmias, coronary artery disease or myocardial infarction within the last 12 months

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neo-adjuvant Erbitux-based chemotherapy<br>Neo-adjuvant Erbitus-based chemotherapy before surgery: Erbitus, Docetaxel, Cisplatin. | Drug: Neo-adjuvant Erbitux-based chemotherapy<br>* Name/Substance: Erbitux Formulation: 2 mg/ml or 5 mg/ml Dose: 400 mg/m^2 initial, and then 250 mg/m^2 weekly Route: Intravenous infusion Frequency & treatment mode: Weekly Duration: 6 weeks Name/Substance: Docetaxel Formulation: Liquid (20 mg/2 ml) Dose: 75 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks Duration: 2 cycles (6 weeks) Name/Substance: Cisplatin Formulation: Powder (30 mg) Dose: 75 mg/m^2 Route: Intravenous infusion Frequency & treatment mode: Day 1, every 3 weeks Duration: 2 cycles (6 weeks)<br>* Other names: Followed by surgery and radiotherapy;|
| No Intervention: Surgery and radiotherapy<br>Surgery and post-operative radiotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response | To evaluate pathological Complete Response (pCR) after neo-adjuvant Erbitux-based chemotherapy followed by surgery and radiotherapy. | Up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Free Survival | Disease Free Survival (DFS) rates (1, 2, 3, 5 years) | 5 years | 
| Locoregional Control rates | Locoregional Control rates (LCR) (1, 3, 5 years) | 5 years | 
| Overall Survival | Overall Survival (OS) rate (3, 5 years) | 5 years | 
| Number of Participants with Adverse Events | All Adverse Events(AEs),including Serious Adverse Events(SAEs), Exposure of All study drugs & radiation | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral cancer, Oropharyngeal cancer, Induction chemotherapy, Targeted chemotherapy, Surgery, Radiotherapy