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
- 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,
- 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.
- Surgery (excluding prior diagnostic biopsy) or irradiation within 4 weeks before
- 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 and/or methotrexate or any of their
- 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