TPF Induction With Concomitant Chemoradiation to Treat Patients With Head and Neck Cancer

Study Overview
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Brief Summary
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The purpose of this trial is to compare two different treatments for fit patients with head and neck cancer: All patients are given induction-chemotherapy (docetaxel, cisplatin, 5-FU). Subsequently patients are being randomised into two groups: The first group receives neo-adjuvant chemotherapy ('high' dose cisplatin) and conventional radiotherapy The second group receives neo-adjuvant chemotherapy ('low' dose cisplatin) and accelerated radiotherapy.

Detailed Description
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Induction Chemotherapy TPF(arm A and B) : Docetaxel 75 mg/m2 iv on day 1, Cisplatin 75 mg/ m2 iv on day 1, 5-FU 750 mg/ m2/day iv continuous infusion (in Hickman or port a cath) on days 1-5; prophylactic G-CSF This cycle will be repeated every 21 days for a maximum of 4 cycles. Clinical evaluation after each cycle and radiological evaluation after 2 cycles will take place. In case of PD or SD (after 2 cycles) with no minor response (no decrease in measurable disease from baseline) concomitant chemoradiotherapy will started per protocol. Surgery The investigators in each centre can decide neck surgery for residual tumor

Official Title
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A Randomised Study of TPF as Neoadjuvant Chemotherapy Followed by Concomitant Chemoradiotherapy (CRT) With Conventional Radiotherapy (RT) Versus Concomitant CRT With Accelerated RT in Patients With Locally Advanced Head and Neck Squamous Cell Cancer (HNSCC) in Good Condition. The Condor Study. A Study of the Dutch Head and Neck Cancer Group (DHNCG).

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Radiation: conventional radiotherapy with 'high' dose cisplatin
* Radiation: accelerated radiotherapy with 'low' dose cisplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histology and staging disease Histologically or cytologically proven non-metastatic locally advanced HNSCC, stage III or IV, for which concomitant chemo-radiotherapy would be the standard therapy Patients can be included either with irresectable disease or for which the concomitant chemoradiotherapy was chosen for organ preservation Measurable disease Primary site: oral cavity, oropharynx, hypopharynx and larynx General conditions Written informed consent Age >18 years and ≤ 65 years WHO performance status 0-1 Adequate bone marrow function (WBC > 3.0 x 109/L, platelets > 100 x 109/L, Hb > 6 mmol/L) Adequate hepatic function: total bilirubin < 1. 5 x upper normal limit, ASAT and ALAT < 2.5 x upper normal limits Adequate renal function: calculated creatinin clearance > 60ml/min. (Cockcroft-Gault formula) Other Expected adequacy of follow-up. Exclusion Criteria: General conditions Active alcohol addiction Admission for COPD in the last 12 months Weight loss > 10% in 3 months before entry Pregnancy or lactation Patients (M/F) with reproductive potential not implementing adequate contraceptives measures Prior or current history Prior surgery, radiotherapy or chemotherapy for this tumor Serious concomitant diseases preventing the safe administration of chemotherapy and/or radiotherapy or likely to interfere with the study assessments Serious active infections Other malignancies in the past 5 years with the exception of adequately treated carcinoma in situ of the cervix, or squamous or basal cell carcinoma of the skin Concomitant treatments Concomitant (or within 4 weeks before randomisation) administration of any other experimental drug under investigation Concurrent treatment with any other anti-cancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: 1<br>Induction Chemotherapy with TPF Then: cisplatin 100 mg/m2 on day 1, 22 and 43 combined with conventional radiotherapy | Radiation: conventional radiotherapy with 'high' dose cisplatin<br>* radiotherapy: 5 fractions/week, total treatment time 7 weeks. Dose to gross tumor volume 70 Gy/35 fractions, dose to elective nodal areas 46 Gy/23 fractions. 100 mg/m2 cisplatin iv on day 1, 22 and 43<br>|
| Active Comparator: 2<br>Induction chemotherapy with TPF Then cisplatin 40mg/m2 on day 1,8,15,22,29 and 35 combined with accelerated radiotherapy | Radiation: accelerated radiotherapy with 'low' dose cisplatin<br>* Accelerated radiotherapy 6 fractions/week, total treatment time 6 weeks. During one of the weekdays two fractions will be delivered with an interval of at least 6h. Dose to gross tumor volume 70 Gy/35 fractions, dose to elective nodal areas 46 Gy/23 fractions cisplatin 40 mg/m2 iv on day 1,8,18,22,29,35<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasibility of both study-arms |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to assess the toxicity profile, tumour response, disease free survival and overall survival in both study-arms. Also QoL will be measured. |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HNSCC, neo Adjuvant, Chemoradiation therapy, TPF