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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Head Neck Cancer Squamous Cell Recurrent

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 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: Cetuximab<br>Dosing schedule: 500 mg/m², every two weeks (q2w) Mode of administration: IV | Drug: Cetuximab<br> <br> |
| Active Comparator: Methotrexate<br>Dosing schedule: 40mg/m2 weekly (q1w) Mode of administration: IV | Drug: Methotrexate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure free survival (FFS) | Composite criteria of efficacy and tolerance: Failure free survival (FFS) defined as time from randomization to the first event among progression (defined by RECIST criteria), treatment stop (whatever the cause), loss of 2 points or more in Activities in Daily Living (ADL) scale and death (whatever the cause). Patients who don't have any of these events are censored at the date of last follow-up. | From randomization to the first event among progression, treatment stop, whatever the cause, loss of 2 points or more in ADL scale and death assessed up to 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | Patients with disease progression will be treated off protocol but will be followed for overall survival evaluation. | From randomization to death from any cause assessed up to 1 months | 
| Progression free survival (PFS) | minimum time from randomization to progression as defined by RECIST criteria or to death from any cause. | From randomization to progression assessed up to 16 months |