Chemotherapy With Cetuximab in Treating Patients With Recurrent or Metastatic Head and Neck Cancer

Study Overview
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Brief Summary
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PURPOSE: Cetuximab with platinum and 5FU is now the standard combination as first-line treatment in patients with metastatic or recurrent Head and Neck squamous cell carcinomas. Cetuximab and taxane combinations have demonstrated promising activity in Head and Neck cancer. This phase II trial is studying new cetuximab, docetaxel and cisplatin combination named TPEx as first-line treatment in this setting.

Detailed Description
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OBJECTIVES: Primary To determine the efficacy of TPEx combination in patients with head and neck cancer in term of objective response rate (RECIST, see statistical consideration) Secondary To assess toxicities of TPEx combination Determine the efficacy of TPEx combination in patients with head and neck cancer: Best Overall Response , progression-free survival and survival. Translational research objective:To better understand the mechanisms of chemoresistance and to identify biomarkers by the analysis of the tumor biopsies (RNA, gene expression profile) and protein profile (plasma samples). Exploratory analyses. OUTLINE: This is an open-label phase II, multicenter study. Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according to the patient or the investigator. Tumor check-up will be performed every 6 weeks. This study will allow translational research with blood sample and biopsies at baseline before any treatment, during the treatment with TPEx combination (week 6).,After completion of study treatment, patients are followed every 2 months.

Official Title
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Phase II Study of Cetuximab, Docetaxel and Cisplatin as First-line Treatment in Patients With Metastatic or Recurrent Head and Neck Squamous Cell Carcinomas - GORTEC 2008-03 TPEx

Conditions
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Squamous Cell Head and Neck Carcinoma, Recurrent or Metastatic Disease

Intervention / Treatment
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* Biological: cetuximab IV
* Other: Biopsies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven squamous cell carcinoma of the oral cavity, larynx, oropharynx or hypopharynx Recurrent disease, incurable disease as determined by surgery or radiation, or metastatic disease Measurable or evaluable disease Age > 18 years and <= 70 years WHO performance status 0 or 1 Absolute neutrophil count > 1,500/mm3 Platelets > 150,000/mm3 Total Bilirubin <= institutional upper limit of normal Aspartate aminotransferase < 1.5 X institutional upper limit of normal Alanine aminotransferase < 1.5 X institutional upper limit of normal Alkaline phosphatase < 2.5 X institutional upper limit of normal creatinine clearance > 60 mL/min Signed informed consent Women of child-bearing potential and men must be willing and able practice adequate contraception prior to study entry and for the duration of study treatment Exclusion Criteria: Previous chemotherapy. Chemotherapy given as part of initial curative therapy and completed more than 6 months before inclusion is allowed Previous treatment with total doses of cisplatin > 300 mg/ m2 Patients must not have any co-existing disease that would preclude cisplatin administration, such as peripheral neuropathy or renal failure Surgery (excluding biopsy) or radiotherapy within 4 weeks prior to study entry Nasopharyngeal carcinoma, or cancer of sinusal cavities Active infection including tuberculosis or HIV positive patient Other malignancy within last 5 years except for non-melanoma skin cancer No other investigational agent within 30 days prior to study entry No other concurrent chemotherapy, immunotherapy, antitumor hormonal therapy (excluding contraceptives and replacement steroids), radiotherapy, or experimental medications No prior anti EGFR therapy No known brain metastases Uncontrolled intercurrent illness that would prevent delivery of protocol therapy Patients with a prior history of basal cell carcinoma of the skin or in situ carcinoma of the cervix must have been curatively treated and must have remained disease free for 5 years post diagnosis No history of hypersensitivity reaction to drugs on study No unstable angina or myocardial infarction within the past 12 months No symptomatic congestive heart failure or New York Heart Association (NYHA) class II-IV heart disease No serious uncontrolled cardiac arrhythmia No other prior or concomitant squamous cell carcinoma No other prior or concomitant cancer, except curatively treated basal carcinoma of the skin or in situ cervical cancer, for which the patient has been curatively treated and remains disease-free for the past 5 years Patient is pregnant or lactating Patients must not have any co-existing condition that would preclude full compliance with the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cetuximab<br>Patients receive four cycles of chemotherapy comprising cetuximab IV plus docetaxel IV over 1 hour and cisplatin IV over 2 hours on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. After completion of the fourth cycle of chemotherapy, patients receive a maintenance therapy with cetuximab every 2 weeks. Treatment will be continued until disease progression or unacceptable toxicities according | Biological: cetuximab IV<br>* Cetuximab 400 mg/m² over 120 minutes on day 1 of cycle 1 only. Cetuximab dose will be 250 mg/m² IV over 60 minutes weekly on subsequent administrations during the four cycles of chemotherapy. Cetuximab dose will be 500mg/m2 IV every 2 weeks during the maintenance therapy. Drug: Cisplatin IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles Drug: Docetaxel IV : 75 mg/m2 intravenous every 3 weeks for 4 cycles G-CSF support with lenograstim 150 microg./m2/day is delivered after each cycle of chemotherapy.<br>Other: Biopsies<br>* No intervention, only biopsy for translational project.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rate | The objective tumor response rate is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT-scan or MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. | 12 weeks (after completion of the 4th cycle of chemotherapy) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 1 to 5 Toxicity | All grade 1 to 5 toxicity are registered during treatment. Patients have weekly clinical and biological examination. | 24 weeks (average) | 
| Best Overall Response | Tumor response is evaluated every 6 weeks according to RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions, Stable Disease (SD); Best overall Response = CR + PR + SD. | 12 weeks | 
| Progression-free Survival |  | 1 year | 
| Overall Survival |  | 1 year | 
| Biomarkers |  | two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous cell carcinoma of the head and neck, recurrent or metastatic, first line chemotherapy, cetuximab, docetaxel, cisplatin, antineoplastic agents, First Line Palliative Treatment