Docetaxel, Cisplatin (TP) + Radiation +/- Cetuximab in Larynx Carcinoma (CA)

Study Overview
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Brief Summary
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The DeLOS II trial is a multicenter randomised phase II trial investigating a TP/5-Fluorouracil (TPF)-chemotherapy with or without cetuximab for Patients with only by laryngectomy operable carcinoma of the larynx/hypopharynx. Patients were divided in responder or non-responder after 4 weeks. Since August 2009 Responder receive TP with or without Cetuximab + radiation. (Until february 2009 Responder received TPF with or without Cetuximab + radiation.) Planned accrual is 85 patients per treatment arm. The primary study endpoint is a confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after randomisation.

Official Title
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Randomised Phase II Screening Study to be Used in an TP/TPF-chemotherapy (Short Induction) Before TP/TPF-induction, Radiotherapy With or Without Cetuximab in the Primary Therapy of the Only by Laryngectomy Operable Carcinoma of the Larynx/Hypopharynx

Conditions
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Squamous Cell Carcinoma of the Hypopharynx, Larynx Carcinoma

Intervention / Treatment
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* Radiation: Radiation
* Drug: Cetuximab
* Drug: Docetaxel
* Drug: Cisplatin (TP)
* Drug: 5-Fluorouracil (TPF) (only until Feb 2009)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed, primary only with laryngectomy respectable squamous-cell carcinoma of the larynx or hypopharynx T3-T4a carcinoma of the glottis T2-T4a carcinoma of the supraglottic, only controllable by laryngectomy and if applicable by root of tongue segmental resection T2-T4a carcinoma of the hypopharynx only controllable by laryngectomy (for example T2, post cricoidal) and hypopharynx segmental resection N-status: cervical metastases (N0-N3) have to be rehabilitate by surgical procedures Blood count: Leukocytes >3500/mm\3, Neutrophils > 1500/ mm\3, Thrombocytes > 8000/ mm\3 Clinical chemistry: adequate renal function, defined by serum creatinine and urea not higher than 25% upper NL, creatinine-clearance > 60 ml/min/1,72 m\2 adequate hepatic function with SGOT, SGPT not higher than 50% and bilirubin not higher than upper NL electrolytes at NL anesthetic risk normal or low-grade elevated age 18-75 years written informed consent effective contraception after individual advice for men and women if there is a possibility of reproductive potential (effective contraception are: oral contraception with estrogen and gestagen (no minipill), vaginal ring, contraception patch, estrogen free ovulation suppressors, hormone spiral with progesterone, injection for three month with depot gestagen, hormone releasing implantation (luteal hormone containing rod), abstinence or sterilization (vasectomy) of the male) Exclusion Criteria: primary cancer treatable by operational larynx -conserving procedures distant metastases (M1-Status) total tumor volume exceeding 80 ml or larynx skeleton punctuated with infiltration of surrounding soft tissues respectively the esophageal aditus (exclusive cartilage infiltration represents no exclusion criteria) tumor-specific prior chemo or radiotherapy metachronous or synchronous malignant tumor (exception basalioma) [in case of a controlled tumor of different localization with a non-treated interval over 5 years to the present therapy the patient can be included after consultation with the coordinating investigator] life expectancy < 3 month Karnofsky performance status < 70% serious cardiopulmonary concomitant disease (cardiac insufficiency grade III and IV according NYHA status, myocardial infarction, angina pectoris, respiratory global insufficiency) Chronic diseases with permanent-therapy (uncontrolled diabetes, active rheumatoid arthritis) recurrent pneumonia, COPD GOLD stage <2, chronic inflammation of intestine or any other concomitant diseases, which disallow study participation in the opinion of the responsible physician Other circumstances (contra-indications), which disallow treatment with Docetaxel, Cisplatin, 5-FU, Cetuximab or radiotherapy Expected absent patient compliance Periodic follow-up not possible (for example address outside germany) Pregnant or breast-feeding woman Absent or constricted legal capacity Participation to another clinical trial with any investigational study within 30 days prior to study screening

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>TP + Radiation (TPF until Feb 2009) | Radiation: Radiation<br>* Radiation start in week 11<br>Drug: Docetaxel<br>* 75 mg/m2 i.v. day 1 3 times<br>* Other names: Taxotere;Drug: Cisplatin (TP)<br>* 75 mg/m2 i.v. day 1 3 times<br>Drug: 5-Fluorouracil (TPF) (only until Feb 2009)<br>* Only patients recruited until Feb 2009: 750 mg/m2 i.v. day 1-5, 3 times<br>|
| Experimental: B<br>TP + Cetuximab + Radiation (TPF until Feb 2009) | Radiation: Radiation<br>* Radiation start in week 11<br>Drug: Cetuximab<br>* Day 1 400mg/m2 i.v. than weekly 250 mg/m2 i.v. for 16 weeks<br>Drug: Docetaxel<br>* 75 mg/m2 i.v. day 1 3 times<br>* Other names: Taxotere;Drug: Cisplatin (TP)<br>* 75 mg/m2 i.v. day 1 3 times<br>Drug: 5-Fluorouracil (TPF) (only until Feb 2009)<br>* Only patients recruited until Feb 2009: 750 mg/m2 i.v. day 1-5, 3 times<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmatory proof of an adequate survival rate with a functionally larynx-conserving 2 years after randomisation |  | LFS-rate 2 years after randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Descriptive analysis of the study arms concerning the secondary end criteria of the study |  | LSF 2 years after randomisation | 
| Explorative comparison of the study arms concerning the primary and secondary end criteria of the study |  | LSF 2 years after randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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by laryngectomy operable carcinoma of the larynx and the hypopharynx