Cetuximab & Concomitant-Boost Accelerated RT in Patients With Locally Advanced Oropharynx Squamous Cell Carcinoma.

Open Label Randomized Phase II, Multicentre, Pilot Study to Evaluate Safety and Efficacy of the Combination of Cetuximab and Concomitant-Boost Accelerated Radiotherapy Followed or Not by a Complementary Treatment With Cetuximab in Patients With Locally Advanced Oropharynx Squamous Cell Carcinoma.

The purpose of this study is to determine the 1-year rate of locoregional disease control in the experimental arm, using a control arm to avoid selection bias.

• To determine the 1-year rate of locoregional disease control in the experimental arm, using a control arm to avoid selection bias.
• To determine the 2 and 3 year rate of locoregional disease control.
• To evaluate the safety and toxicity of the combination of cetuximab and concomitant-boost accelerated radiotherapy followed by 12 weeks of complementary treatment with cetuximab. Both acute and chronic toxicity will be assessed.
• To determine specific disease-free survival, event-free survival, disease-specific survival and overall survival
• To determine acute and late toxicity
• To determine EGFR, p53, Ki67, and evaluate its value as a prognostic factor.

Inclusion Criteria:

• Written informed consent.
• Aged between 18 and 80, inclusive.
• Karnofsky functional status >= 70% at the time of enrolment in study.
• Life expectancy of more than 3 months.
• Histologically confirmed diagnosis of oropharyngeal squamous cell carcinoma: base of tongue, vallecula, tonsil and tonsillar fossa and pillars, glossotonsillar sulcus, inferior surface of the soft palate, uvula and lateral and posterior oropharyngeal wall.
• Stage III or IV with no evidence of distant metastasis (IVA or IV B)
• Patients in medical conditions to receive a radical concomitant-boost accelerated radiotherapy treatment.
• Neutrophils >= 1500/ mm3, platelet count >= 100 000/ mm3 and haemoglobin >= 10 g/ dL.
• Proper liver function: total bilirubin <= 1.5 x upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN.
• Proper renal function: serum creatinine <= 1.5 x ULN; if the values are > 1.5 x ULN, creatinine clearance should be >= 55 ml/min.
• Serum calcium within normal limits.
• Adequate nutritional state: weight loss < 20% with respect to usual weight and serum albumin > 35 g/l.
• Effective birth control method if there is possibility of conception and/or pregnancy.
• Availability of tumour tissue for immunohistochemical analysis of EGFR expression.

Exclusion Criteria:

• Metastatic disease.
• Previous surgical, radiotherapy and/or chemotherapy treatment for the disease in the study.
• Other non-oropharyngeal tumour sites in the head and neck area.
• Other previous and/or simultaneous squamous cell carcinoma.
• Diagnosis of any other cancer in the previous 5 years, except properly treated carcinoma in situ of the uterine cervix and/or basal cell skin carcinoma.
• Active infection (infection requiring intravenous antibiotics), including active tuberculosis and diagnosed HIV.
• Uncontrolled hypertension defined as systolic blood pressure >= 180 mm Hg and/or diastolic blood pressure >= 130 mm Hg at rest.
• Pregnancy (absence of pregnancy must be confirmed with the serum-HCG test) or breast-feeding women.
• Chronic, concomitant systemic immunotherapy, or hormonal treatment for the cancer.
• Other concomitant anti-cancer treatments.
• Clinically significant coronary artery disease, history of myocardial infarction in the previous 12 months or high risk of out of control arrhythmia or cardiac insufficiency.
• Chronic obstructive pulmonary disease which may have required > 3 hospitalisations in the previous 12 months.
• Out of control active peptic ulcer.
• Presence of a psychological or medical illness which might impede the patient from carrying out the study or giving his or her signature on the informed consent
• Known drug abuse (with the exception of excessive alcohol consumption)
• Known allergic reaction to any of the components of the treatment to be studied.
• Previous treatment with monoclonal antibodies or signal transduction inhibitors or other EGFR-targeted treatment.
• Any experimental treatment in the 30 days prior to enrolment in the study.