Phase III Trial Comparing Methotrexate and Cetuximab in First-line Treatment of Recurrent and/or Metastatic Squamous Cell Head and Neck Cancer

Multicentric Randomized Phase III Trial Comparing Methotrexate and Cetuximab in First-line Treatment of Recurrent and/or Metastatic Squamous Cell Head and Neck Cancer in Elderly Unfit Patients According to Geriatric Evaluation

To test whether cetuximab improves efficacy/tolerance as compared to methotrexate in first line treatment of unfit patients ³ 70 years old with recurrent and /or metastatic HNSCC. Efficacy assessed by failure free survival

Inclusion Criteria:

• Patients aged 70 or over
• Included in ELAN-ONCOVAL study and considered as "Unfit" by geriatric evaluation done in this study
• PS < 3
• Histologically confirmed diagnosis of squamous cell carcinoma of head and neck: oral cavity, oropharynx, hypopharynx, larynx.
• Recurrence and/or metastatic disease not suitable for local therapy.
• At least one measurable lesion (RECIST 1.1) by CT or MRI.
• No brain metastasis.
• Clearance of creatinine >= 50ml/mn (MDRD).
• Adequate haematological functions defined as follows: absolute neutrophil count > 1.5 x 109/l, platelet > 100 x 109/l, hemoglobin >= 9.5 g/dl
• Adequate hepatic functions with serum total bilirubin <1.25 Upper limit of normal range (ULN); SGOT/SGPT < 5 ULN; AP < 5 ULN
• Life expectancy > 12 weeks.
• Males of reproductive potential must agree to use an effective contraceptive method during the treatment and after the end of treatment during five months.
• Signed informed consent.
• Affiliated to Health Insurance regimen (according to Public Health Law of August 9, 2004).

Exclusion Criteria:

• Included in ELAN-ONCOVAL study and considered as "Fit" by geriatric evaluation
• Patients with nasopharyngeal cancer, paranasal sinus, or cervical lymph nodes metastasis of unknown origin.
• Prior systemic chemotherapy for the squamous cell carcinoma of head and neck, except if given as part of a multimodal treatment for locally advanced disease which was completed more than 6 months prior to study entry.
• Prior anti-EGFR therapy, except if given in association with radiotherapy for squamous cell carcinoma of head and neck which was completed more than 12 months prior to study entry.
• Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before study entry.
• Brain metastasis
• Active infection including tuberculosis and HIV infection.
• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III or IV), unstable angina pectoris, history of myocardial infarction within the last twelve months, significant arrhythmias
• Concomitant immunotherapy or antitumoral hormonotherapy.
• Requirement for treatment with any of the prohibited concomitant medications listed in SPC of Cetuximab and Methotrexate. In particular, acetylsalicylic acid used at analgesic, antipyretic or anti-inflammatory doses (see Section 6.3.2).
• Malignancies within 5 years prior to randomization, with the exception of adequately treated basal or squamous cell skin cancer and carcinoma in situ of the cervix
• Known allergic hypersensitivity to cetuximab or known positive results of tests for IgE antibodies against cetuximab (α-1-3-galactose) and/or methotrexate or any of their excipients.
• Other severe acute or chronic psychiatric or medical condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient's safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study