Cetuximab and Combination Chemotherapy in Patients With Stage III-IV Resectable Oropharynx Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel, cisplatin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) together with cetuximab may kill more tumor cells. PURPOSE: This phase II clinical trial is studying how well cetuximab given together with combination chemotherapy works in treating patients with stage III or stage IV oropharynx cancer that can be removed by surgery.

Detailed Description
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OBJECTIVES: Primary To determine the complete clinical response rate at 3 months in patients with stage III or IV nonmetastatic squamous cell carcinoma of the oropharynx treated with cetuximab, docetaxel, cisplatin, and fluorouracil. Secondary To determine the rate of tumor response. To determine progression-free and overall survival. To determine the rate of complete pathological response. To assess the tolerability of this regimen in these patients. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours on days 1, 8, and 15; docetaxel IV over 1 hour and cisplatin IV over 1 hour on day 1; and fluorouracil IV continuously on days 1-5. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 2 months for 1 year and every 3 months for 2 years.

Official Title
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Induction Chemotherapy With Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (ETPF) in Patient With Resectable Stage III-IV Squamous Cell Carcinoma of the Oropharynx

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: docetaxel
* Drug: fluorouracil
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed squamous cell carcinoma of the oropharynx Stage III (T3 or T1-2, N1-2, M0) or nonmetastatic stage IV (T4 or T1-3, N3, M0) disease Resectable disease Measurable or evaluable disease Tumor tissue available PATIENT CHARACTERISTICS: Inclusion criteria: WHO performance status 0-1 ANC ≥ 1,500/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 9 g/dL Creatinine < 1.5 times upper limit of normal (ULN) Creatinine clearance ≥ 60 mL/min AST and ALT < 5 times ULN Bilirubin < 1.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception Affiliated with social security (including CMU) Exclusion criteria: Cardiovascular accident (myocardial infarction, cerebral vascular accident) within the past 6 months Serious and/or uncontrolled cardiac or respiratory disease (pulmonary fibrosis, interstitial pneumopathy) Other cancer within the past 5 years except for resected skin cancer, localized cutaneous or totally resected melanoma, or resected carcinoma in situ of the cervix Auditory condition precluding the use of cisplatin Contraindication due to psychological, social, or geographical reasons that may impede proper monitoring of treatment Persons under guardianship or trusteeship, or prisoners of law PRIOR CONCURRENT THERAPY: No prior treatment, including chemotherapy or radiotherapy No concurrent phenytoin, live attenuated vaccines, or parenteral aminoglycosides

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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>Cetuximab by intravenous (IV) infusion over 1-2 h on day | Drug: cisplatin<br>* 75 mg/m², day 1. 3 cycles<br>Drug: docetaxel<br>* 75 mg/m² Day 1. 3 cycles<br>Drug: fluorouracil<br>* 750 mg/m² day 1 to day 5. 3 cycles<br>Drug: Cetuximab<br>* 400 mg/m² Day 1, 250 mg/m² Day 8 and Day 15. 3 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months | The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination | at 3 months after ETPF combination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Clinical Response (cCR) | Clinical complete response (cCR) is defined by: Disappearance of all clinical evidence of visible tumor, Disappearance of all palpable residual infiltration, Disappearance of all evidence of residual visible tumor on CT scan in pharynx and parapharyngeal space, Complete symmetric remobilization of the tongue and amygdala. Disappearance of pre-existing trismus. Negative control biopsy. The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination | at 3 months | 
| The 2-year Estimated Overall Survival (OS) Rate | 2-year OS measured survival at 2 years from randomization. | 2 years | 
| Pathologic Response | On primary tumor resected : measure of persistence or not of tumoral lesion, histological type, size and quality of the excision piece A pathological complete response is defined as no viable tumour cells detected on histological examination post surgery. | after surgery of the primary tumor | 
| The 2-year Estimated Progression-free Survival (PFS) | 2-year PFS measured survival at 2 years from randomization. | 2 years | 
| Complete Radiological Response (rCR) | Radiological response is defined according to RECIST 1.0 criteria: Complete response (CR): disappearance of all target lesions Partial response (PR): at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter, Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target the appearance of one or more new lesions, Stable disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started | At 3 months after the end of 3 cycles of the ETPF combination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III squamous cell carcinoma of the oropharynx, stage IV squamous cell carcinoma of the oropharynx, tongue cancer