Chemoradiation Treatment for Head and Neck Cancer

Study Overview
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Brief Summary
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This is a Phase II study of cetuximab, carboplatin and radiotherapy (RT) in patients with Locally Advanced Head and Neck Carcinomas (LAHNC) who are unfit for cisplatin. The aim of this study is to show the feasibility and safety profile of the combination of cetuximab, carboplatin and RT in treatment of patients with LAHNC.

Detailed Description
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Secondary objectives are to estimate failure free survival (FFS) and overall survival, to evaluate the time to local and regional failure and to determine the site of first failure (characterised as local, regional, distant or combinations). Acute and late treatment toxicities will also be evaluated.

Official Title
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A Phase II Study of Cetuximab, Carboplatin and Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Cetuximab
* Drug: Carboplatin
* Radiation: Radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated SCC of the oropharynx, larynx or hypopharynx. Stage III or IV, excluding T1N1, and metastatic disease (to be confirmed by a chest CT, and abdominal CT or ultrasound scan if patients with abnormal liver function tests or a bone scan or FDG-PET if patients with bone pain). Histologically or cytologically confirmed HNSCC Disease must be considered potentially curable by chemoradiation Patients medically unfit for cisplatin chemotherapy due to one or more of the following reasons: Clinically significant sensori-neural hearing impairment (audiometric abnormalities without corresponding clinical deafness will not be regarded as a contraindication to cisplatin) Severe tinnitus Renal impairment (GFR < 60ml/min) Peripheral neuropathy > grade 2 Inability to tolerate intravenous hydration eg due to cardiac disease Co-morbidities (based on clinical judgement by the investigator) associated with ECOG PS 2 that in the view of the investigator would preclude the safe administration of cisplatin Performance status ECOG 0, 1 or 2. Adequate haematological, renal and hepatic functions as defined by: Absolute neutrophil count (ANC, segmented cells (segs) + bands)>= 1.5 x 109/L Platelet count >= 100 x 109/L Total bilirubin <= 1.5 x upper normal limit Alanine aminotransferase <= 2.5 x upper normal limit Calculated creatinine clearance > 40ml/min (Cockcroft-Gault formula). If calculated creatinine clearance < 50 ml/min, glomerular filtration rate to be measured with DTPA or EDTA scan. If < 40 ml/min not eligible. Age >18 years Signed written consent Suitable for follow-up for 4 years in the view of the investigator Exclusion Criteria: Distant metastases, i.e., any metastatic disease below the clavicles. Patients with lung nodules >10mm will be excluded unless non-malignancy aetiology is established. Patients with lesions 5-10mm can be included if a FDG-PET scan is negative and the investigator considers on clinical grounds that metastasis is unlikely. Patients with lesions < 5mm can be included if the investigator considers on clinical grounds that metastases are unlikely. Patients with multiple lung nodules should not be included unless there is a strong case that these do not represent metastases, e.g., stable on imaging for over 12 months, non-malignant aetiology apparent. The level of clinical suspicion may be influenced by clinical stage, e.g., N3 disease, low neck nodes. In general if there is any doubt patients should be excluded. Previous radical RT to the head & neck region, excluding superficial RT for a non-melanomatous skin cancer. Patients with prior cancers, except: those diagnosed > 5 years ago with no evidence of disease recurrence and clinical expectation of recurrence of less than 5%; or successfully treated non-melanoma skin cancer; or carcinoma in situ of the cervix. Significant intercurrent illness that will interfere with the chemotherapy or radiation therapy such as HIV infection, cardiac failure, pulmonary compromise, active infection Any history of myocardial infarction, ventricular arrhythmias, or unstable angina within the last 6 months Pregnant or lactating women. Weight loss greater than 20 % of usual body weight in the 3 months preceding trial entry High risk for poor compliance with therapy or follow up as assessed by the investigator Prior radiation to greater than 30% of the bone marrow Prior systemic chemotherapy for cancer Refusal by male or female patients, to use appropriate contraception during the study and for 3 months afterwards Any condition or circumstance which might prevent the patient being able to give valid informed consent, or from completing participation in the study

Ages Eligible for Study
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Minimum Age: 18 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: Single arm<br>Chemoradiation (Cetuximab, Carboplatin and Radiotherapy) | Drug: Cetuximab<br>* Patients will receive weekly intravenous cetuximab (initial dose 400mg/m2 in the week prior to commencing radiotherapy, then weekly 250mg/m2)for the duration of the radiotherapy<br>* Other names: Erbitux;Drug: Carboplatin<br>* Weekly intravenous carboplatin (AUC 2) for the duration of the RT<br>* Other names: Paraplatin;Radiation: Radiotherapy<br>* The radiotherapy schedule will be the infield boost (IFB) regimen, that is 66 Gy in 35 fractions over 5 weeks: daily for 3 weeks, then twice daily for 2 weeks (or 70 Gy in 35 fractions over 7 weeks for a specific subgroup of patients where IFB is not recommended).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Feasibility |  | An initial 6 patients will be treated. Once all these patients have a 2 week post RT review there will be analysis. If <= 1 patient has a DLT than the treatment is deemed safe. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure free survival (FFS) |  | All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment. | 
| Time to local and/or regional failure |  | All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment. | 
| Overall survival |  | All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment. | 
| Site of first failure |  | All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment. | 
| Acute and late treatment toxicities |  | All patients will be followed until the last patient enrolled has a minimum follow up of 2 years post treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck, Cetuximab, Carboplatin, Radiotherapy