TPF Plus Cisplatin and Radiotherapy vs TPF Plus Cetuximab and Radiotherapy to Treat Head and Neck Cancer.

Study Overview
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Brief Summary
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An Open Label Randomized, Multi-Centre Phase III Trial of TPF Chemotherapy Plus Concomitant Treatment With Cisplatin and Conventional Radiotherapy Versus TPF Chemotherapy Plus Concomitant Cetuximab and Conventional Radiotherapy in Locally Advanced, Unresectable Head and Neck Cancer.

Detailed Description
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This study is being sponsored by a cooperative medical group.

Official Title
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Open Label Randomized, Multi-centre Phase III Trial of TPF Plus Concomitant Treatment With Cisplatin and Radiotherapy Versus Concomitant Cetuximab and Radiotherapy in Locally Advanced, Unresectable Head and Neck Cancer.

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Other: TPF, radiotherapy and cisplatin.
* Other: TPF, radiotherapy and cetuximab.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Before the beginning of protocol's specific procedures, the informed consent has to be obtained. Locally advanced cancer of head and neck (oral cavity, oropharynx, larynx and hypopharynx) stage III-IV, without evidence of metastasis. The tumor must be considered to be non-operable according to the criteria of the Northern California Oncology Group. The reason of non-surgical resection will be annotated in the CRF. Criteria of non-surgical resection according to the NCOG: 3.1.Technically not resectable (includes: evidence of mediastinal dissemination; fixed tumor to the clavicle, base of the cranium or cervical vertebrae; affectation of the nasopharynx). 3.2.Medical criteria based on a low surgical curability. 3.3.Medical contraindication for the surgery. Epidermoid carcinoma histologically demonstrated Measurable disease according to the RECIST criteria . Men or women with age between 18 and 70 years, both inclusive. Functional condition index according to ECOG scale:0-1 Patients in medical conditions to be able to receive treatment with TPF induction followed by normofractionated radiotherapy with cetuximab or cisplatin. Patients with adequate hematologic function: neutrophils superior or equal to 2 x 109, platelets superior or equal to 100 x 109, hemoglobin superior or equal to 10 g/dl. Adequate hepatic function: bilirubin lower or equal to 1 x top normal Limit, GOT and GPT lower or equal to 2,5 Top Normal Limit , alkaline phosphatase < 5 Top Normal Limit. Adequate renal function: creatinin <1,4 mg/dl (120 µmol/l); if the values are > 1,4 mg/dl, the clearance of creatinin will have to be > 60 ml/min (real or calculated for Cockcroft-Gault's method). Calcium lower or equal to 1,25 x top normal limit. Adequate nutritional condition: loss of weight <20% with relation to the theoretical weight and albumin superior or equal to 35 g/L. Patients must be accessible for the treatment and the follow-up. Exclusion Criteria: Metastatic disease Surgical treatment, previous radiotherapy and/or chemotherapy for the study disease. Other tumor locations in head and neck that are not oral cavity, oropharynx, larynx, hypopharynx. Other stages that are not III or IVM0. Other previous and / or synchronic squamous carcinoma. Diagnosis of another neoplasia in the last 5 years, excepting carcinoma in situ of uterine neck and/or a cutaneous carcinoma basocellular properly treated. Active infection(at needs endovenous antibiotics), including active tuberculosis and diagnosed HIV. Not controlled hypertension defined as arterial systolic tension superior or equal to 180 mm Hg and / or diastolic arterial tension superior or equal to 130 mm Hg baseline. Pregnancy(absence must be confirmed with the test of beta-HCG) or period of lactation. Immunity systemic treatment, chronic and concomitant, or hormonal treatment of the cancer. Other antineoplastic concomitant treatments. Coronary clinically significant arteriopathy or precedents of myocardial infarction in the last 12 months or high risk of not controlled arrhythmia or cardiac not controlled insufficiency. Pulmonary obstructive chronic disease that had needed 3 or more hospitalizations in the last 12 months. Active non controlled peptic ulcer. Presence of a psychological or medical disease that could prevent to accomplish the study by the patient or to grant his/her signature in the informed consent form. Known drugs abuse (with the exception of excessive consumption of alcohol) Known allergic reaction to some of the components of the treatment of the study. Previous treatment with monoclonal antibodies or other transduction of the sign inhibitors or treatment directed against the EGFR. Any experimental treatment in 30 days before the entry in 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group A<br>TPF plus concomitant treatment with cisplatin and conventional radiotherapy. | Other: TPF, radiotherapy and cisplatin.<br>* 3 cycles of: cisplatin: 75 mg/m2, i.v., 1 hour, once daily docetaxel: 75 mg/m2, i.v., 1 hour, once daily 5-fluorouracil: 750 mg/m2, i.v., 24 hours, 5 days Radiotherapy: 70Gy, divided into daily doses of 2 Gray (total days: 35) Cisplatin: 100 mg/m2, i.v., 1 hour, 3 days<br>* Other names: TPF plus radiotherapy and cisplatin;|
| Experimental: Group B<br>TPF plus concomitant treatment with cetuximab and conventional radiotherapy | Other: TPF, radiotherapy and cetuximab.<br>* 3 cycles of: cisplatin: 75 mg/m2, i.v., 1 hour, once daily docetaxel: 75 mg/m2, i.v., 1 hour, once daily 5-fluorouracil: 750 mg/m2, i.v., 24 hours, 5 days Radiotherapy: 70Gy, divided into daily doses of 2 Gray (total days: 35) Cetuximab: 400 mg/m2, i.v, 2 hours, 1 day Cetuximab: 250 mg/m2, i.v, 1 hour, 7 days<br>* Other names: TPF plus radiotherapy and cetuximab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global survival | The time from the start of induction chemotherapy with TPF to death due to any cause or to the last check-up in the case of living patients | Up to 89 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | The response rate (CR + PR) measured using the RECIST 1.0 method. | Up to 89 months | 
| Progression free-survival (PFS) | Time to progression as the time since the start date of treatment with TPF induction chemotherapy until the time when DP occurred or death occurred due to any cause. | Up to 89 months | 
| Time to loco-regional control of disease | As permanent and complete resolution of the disease in terms of its initial site and lymph nodes (T and N). If the disease lasted (regardless of size), the tumor recurred, or a second tumor appeared in the field RT, it will be recorded as a therapeutic failure. | Up to 89 months | 
| Satisfaction with treatment. Analysis of QoL in both treatment arms. | EORTC QoL questionnaires: C30 version 3.0 and QLQ-H&N35 module | Up to 89 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Head and Neck Cancer