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

Oropharynx Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01108042
• Other study ID #: TISOC-1
• Secondary ID: 2009-011902-41
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 14, 2010
• Last updated: May 17, 2016
• Start date: November 2009
• Est. completion date: February 2016

Study information

• Verified date: May 2016
• Source: University of Jena
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: February 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Squamous Cell
• Oropharynx Cancer
• Squamous Cell Carcinoma of the Oral Cavity

Intervention

Drug:
• 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. Phase 2: Optimal dose of phase 1 will be given.

Locations

Country	Name	City	State
Germany	Städt. Kliniken Bielefeld gem. GmbH	Bielefeld
Germany	Friedrich-Schiller-University Jena	Jena
Germany	Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde	Leipzig
Germany	Klinikum Ernst von Bergmann	Potsdam

Sponsors (1)

Lead Sponsor	Collaborator
Orlando Guntinas-Lichius, Prof. Dr. med.

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of progression-free survival after 2 years		24 months	No
Secondary	Overall survival after 2 years		after 2 years	No
Secondary	Determination of the efficacy of the induction therapy	CT or magnetic resonance tomography (MRT) of the neck region	after 1, 12 and 24 months	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes