TPF-Induction Chemotherapy of Oropharyngeal and Cavity of the Mouth Cancer

Study Overview
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Brief Summary
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A combination therapy of Docetaxel, Cisplatin und 5-Fluorouracil (= TPF) will be used in patients with resectable oropharyngeal and cavity of the mouth cancer. To improve the compatibility of the TPF-induction without decreasing the efficacy the dose will be given on day 1 and 8 instead of applying the whole dose on day 1 every 3 weeks. In the phase I-part of the trial the optimal therapeutic dose of Docetaxel and Cisplatin will be defined. In the phase II-part the progression-free survival after 2 years will be assessed in patients treated with the optimal therapeutic dose.

Detailed Description
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Local advanced Oropharyngeal and cavity of the mouth Cancer are often treated with a combination of surgery and/or radiation and /or chemotherapy. Despite of therapy improvement there are only little advances in progression-free survival and overall survival. Therefore new therapy concepts are needed. The advantage of the induction chemotherapy is the possibility of tumor response assessment during chemotherapy and may present a selection criterion for organ preservation. In order to minimize the time between chemotherapy and surgery it is important to have an early answer for the tumor response. In this study response will be assessed after the first cycle of chemotherapy. Patients showing no tumor response will be operated at once. The other patients will receive further cycles of chemotherapy. Toxicity of the induction chemotherapy have to be moderate because surgery should not be delayed. To improve the tolerance of induction therapy the medication dose isn't given on day 1 every 3 weeks, but is dispersed on day 1 and day 8, q3weeks.

Official Title
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Phase I/II Study of Split-dose TPF-Induction Chemotherapy Before Surgery of Oropharyngeal and Cavity of the Mouth Cancer

Conditions
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Oropharynx Cancer, Squamous Cell Carcinoma of the Oral Cavity

Intervention / Treatment
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* Drug: Taxotere, Cisplatin, 5-Fluorouracil (5-FU)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological proven, resectable squamous epithelial carcinoma of the oropharynx and the cavity of the mouth R0-resection possible All T N2 M0 / all T N3 M0 / if T3 or T4a also N0-1 M0 Leucocytes > 4000/mm³ bzw. neutrophils > 2000/mm³, thrombocytes > 100000/mm³ adequate kidney function, defined as serum creatinine und urea in normal range, Creatinine clearance > 60 ml/min adequate liver function with glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and bilirubin in normal range electrolytes in normal range risks of anesthesia complications normal or minor increased Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky >= 60% Age 18 - 80 years signed written informed consent effective contraception for both male and female subjects if the risk of conception exists Exclusion Criteria: T1 N0 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0 Resection without curative intention: primary tumor is not treatable with resection methods Infiltration of the lower jaw M1 status Tumor not measurable with Innovation Center Computer Assisted Surgery (ICCAS) methods No prior chemotherapy or radiation (a primary surgery is allowed) Metachronous or oder synchronous malignoma (Exception: basal cell carcinoma) Life expectance < 3 months ECOG > 2; Karnofsky < 60% acute infections or fever known HIV-infection or other immune suppression severe cardio pulmonary concomitant diseases chronic disease with continuous therapy (uncontrolled diabetes, rheumatoid arthritis) especially continuous therapy with steroids other concomitant diseases which, in the investigator's opinion, would exclude the patient from the study Contraindications which permit a therapy with Docetaxel, Cisplatin, 5-FU or radiation therapy missing patient's compliance regular Follow-up visits not possible Pregnancy or lactation period legal incapacity or limited legal capacity Participation in another clinical trial or administration of a not approved substance within 30 days before registration

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Taxotere, Cisplatin, 5-Fluorouracil (5-FU)<br>Phase 1: Intravenous infusion of 40 mg/m² Taxotere and 40 mg/m² Cisplatin followed by 24 h-infusion of 2000 mg/m² 5-FU on day 1 and day 8 every 3 weeks. If possible an escalation to 50 mg/m² Taxotere and 50 mg/m² Cisplatin can be carried out. | Drug: Taxotere, Cisplatin, 5-Fluorouracil (5-FU)<br>* Phase 1: Intravenous infusion of 40 mg/m² Taxotere and 40 mg/m² Cisplatin followed by 24 h-infusion of 2000 mg/m² 5-FU on day 1 and day 8 every 3 weeks. If possible an escalation to 50 mg/m² Taxotere and 50 mg/m² Cisplatin can be carried out. Phase 2: Optimal dose of phase 1 will be given.<br>* Other names: Docetaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of progression-free survival after 2 years |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival after 2 years |  | after 2 years | 
| Determination of the efficacy of the induction therapy | CT or magnetic resonance tomography (MRT) of the neck region | after 1, 12 and 24 months | 
| Function of swallowing according the penetration-aspiration-scale | assessed according the penetration-aspiration-scale (PAS, Rosenbek et al. 1996) and according measuring after Prosiegel (Prosiegel et al. 2002). | 0,1, 6, 12, 18, 24 months | 
| Adverse events as a measure of safety and tolerability | The number of patients with adverse events will be evaluated. Adverse events will be assessed according Common Terminology Criteria of Adverse Events (CTCAE) v.3.0 and analysed as number per patient and number per cycle. | once a week | 
| Quality of life | European Organisation for Research and Treatment of Cancer (EORTC) Quality of life questionnaire (QLQ) for head and neck cancer patients (HN35) questionnaire filled in by the patients | 0,1, 6, 12, 18, 24 months |