Oropharynx Cancer, Squamous Cell Carcinoma of the Oral Cavity
Conditions
Brief summary
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
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.
Interventions
DRUGTaxotere, Cisplatin, 5-Fluorouracil (5-FU)
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.
Sponsors
Orlando Guntinas-Lichius, Prof. Dr. med.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Histological proven, resectable squamous epithelial carcinoma of the oropharynx and the cavity of the mouth 2. R0-resection possible 3. All T N2 M0 / all T N3 M0 / if T3 or T4a also N0-1 M0 4. Leucocytes \> 4000/mm³ bzw. neutrophils \> 2000/mm³, thrombocytes \> 100000/mm³ 5. adequate kidney function, defined as serum creatinine und urea in normal range, Creatinine clearance \> 60 ml/min 6. adequate liver function with glutamate oxaloacetate transaminase (SGOT), glutamate pyruvate transaminase (SGPT) and bilirubin in normal range 7. electrolytes in normal range 8. risks of anesthesia complications normal or minor increased 9. Eastern Cooperative Oncology Group (ECOG) 0-2 / Karnofsky \>= 60% 10. Age 18 - 80 years 11. signed written informed consent 12. effective contraception for both male and female subjects if the risk of conception exists
Exclusion criteria
13. T1 N0 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0 14. Resection without curative intention: primary tumor is not treatable with resection methods 15. Infiltration of the lower jaw 16. M1 status 17. Tumor not measurable with Innovation Center Computer Assisted Surgery (ICCAS) methods 18. No prior chemotherapy or radiation (a primary surgery is allowed) 19. Metachronous or oder synchronous malignoma (Exception: basal cell carcinoma) 20. Life expectance \< 3 months 21. ECOG \> 2; Karnofsky \< 60% 22. acute infections or fever 23. known HIV-infection or other immune suppression 24. severe cardio pulmonary concomitant diseases 25. chronic disease with continuous therapy (uncontrolled diabetes, rheumatoid arthritis) especially continuous therapy with steroids 26. other concomitant diseases which, in the investigator's opinion, would exclude the patient from the study 27. Contraindications which permit a therapy with Docetaxel, Cisplatin, 5-FU or radiation therapy 28. missing patient's compliance 29. regular Follow-up visits not possible 30. Pregnancy or lactation period 31. legal incapacity or limited legal capacity 32. Participation in another clinical trial or administration of a not approved substance within 30 days before registration
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Determination of progression-free survival after 2 years | 24 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival after 2 years | after 2 years | — |
| Determination of the efficacy of the induction therapy | after 1, 12 and 24 months | CT or magnetic resonance tomography (MRT) of the neck region |
| Function of swallowing according the penetration-aspiration-scale | 0,1, 6, 12, 18, 24 months | assessed according the penetration-aspiration-scale (PAS, Rosenbek et al. 1996) and according measuring after Prosiegel (Prosiegel et al. 2002). |
| Adverse events as a measure of safety and tolerability | once a week | 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. |
| Quality of life | 0,1, 6, 12, 18, 24 months | 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 |
Countries
Germany
Outcome results
None listed