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

Phase 1
Completed
Conditions
Squamous Cell Carcinoma of the Oral Cavity
Oropharynx Cancer
Interventions
Registration Number
NCT01108042
Lead Sponsor
Orlando Guntinas-Lichius, Prof. Dr. med.
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
71
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
  1. T1 N0 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0
  2. Resection without curative intention: primary tumor is not treatable with resection methods
  3. Infiltration of the lower jaw
  4. M1 status
  5. Tumor not measurable with Innovation Center Computer Assisted Surgery (ICCAS) methods
  6. No prior chemotherapy or radiation (a primary surgery is allowed)
  7. Metachronous or oder synchronous malignoma (Exception: basal cell carcinoma)
  8. Life expectance < 3 months
  9. ECOG > 2; Karnofsky < 60%
  10. acute infections or fever
  11. known HIV-infection or other immune suppression
  12. severe cardio pulmonary concomitant diseases
  13. chronic disease with continuous therapy (uncontrolled diabetes, rheumatoid arthritis) especially continuous therapy with steroids
  14. other concomitant diseases which, in the investigator's opinion, would exclude the patient from the study
  15. Contraindications which permit a therapy with Docetaxel, Cisplatin, 5-FU or radiation therapy
  16. missing patient's compliance
  17. regular Follow-up visits not possible
  18. Pregnancy or lactation period
  19. legal incapacity or limited legal capacity
  20. Participation in another clinical trial or administration of a not approved substance within 30 days before registration

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Taxotere, Cisplatin, 5-Fluorouracil (5-FU)Taxotere, 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.
Primary Outcome Measures
NameTimeMethod
Determination of progression-free survival after 2 years24 months
Secondary Outcome Measures
NameTimeMethod
Overall survival after 2 yearsafter 2 years
Quality of life0,1, 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

Determination of the efficacy of the induction therapyafter 1, 12 and 24 months

CT or magnetic resonance tomography (MRT) of the neck region

Function of swallowing according the penetration-aspiration-scale0,1, 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 tolerabilityonce 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.

Trial Locations

Locations (4)

Klinikum Ernst von Bergmann

🇩🇪

Potsdam, Germany

Friedrich-Schiller-University Jena

🇩🇪

Jena, Germany

Städt. Kliniken Bielefeld gem. GmbH

🇩🇪

Bielefeld, Germany

Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde

🇩🇪

Leipzig, Germany

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