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

Primary Purpose

Oropharynx Cancer, Squamous Cell Carcinoma of the Oral Cavity

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Taxotere, Cisplatin, 5-Fluorouracil (5-FU)
Sponsored by
Orlando Guntinas-Lichius, Prof. Dr. med.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Oropharynx Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Städt. Kliniken Bielefeld gem. GmbH
  • Friedrich-Schiller-University Jena
  • Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde
  • Klinikum Ernst von Bergmann

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Taxotere, Cisplatin, 5-Fluorouracil (5-FU)

Arm Description

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.

Outcomes

Primary Outcome Measures

Determination of progression-free survival after 2 years

Secondary Outcome Measures

Overall survival after 2 years
Determination of the efficacy of the induction therapy
CT or magnetic resonance tomography (MRT) of the neck region
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).
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.
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

Full Information

First Posted
April 14, 2010
Last Updated
May 17, 2016
Sponsor
Orlando Guntinas-Lichius, Prof. Dr. med.
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1. Study Identification

Unique Protocol Identification Number
NCT01108042
Brief Title
TPF-Induction Chemotherapy of Oropharyngeal and Cavity of the Mouth Cancer
Official Title
Phase I/II Study of Split-dose TPF-Induction Chemotherapy Before Surgery of Oropharyngeal and Cavity of the Mouth Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Orlando Guntinas-Lichius, Prof. Dr. med.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Oropharynx Cancer, Squamous Cell Carcinoma of the Oral Cavity

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Taxotere, Cisplatin, 5-Fluorouracil (5-FU)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Taxotere, Cisplatin, 5-Fluorouracil (5-FU)
Other Intervention Name(s)
Docetaxel
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determination of progression-free survival after 2 years
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Overall survival after 2 years
Time Frame
after 2 years
Title
Determination of the efficacy of the induction therapy
Description
CT or magnetic resonance tomography (MRT) of the neck region
Time Frame
after 1, 12 and 24 months
Title
Function of swallowing according the penetration-aspiration-scale
Description
assessed according the penetration-aspiration-scale (PAS, Rosenbek et al. 1996) and according measuring after Prosiegel (Prosiegel et al. 2002).
Time Frame
0,1, 6, 12, 18, 24 months
Title
Adverse events as a measure of safety and tolerability
Description
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.
Time Frame
once a week
Title
Quality of life
Description
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
Time Frame
0,1, 6, 12, 18, 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Orlando Guntinas-Lichius, Prof. Dr.
Organizational Affiliation
Friedrich-Schiller-University Jena
Official's Role
Principal Investigator
Facility Information:
Facility Name
Städt. Kliniken Bielefeld gem. GmbH
City
Bielefeld
ZIP/Postal Code
33604
Country
Germany
Facility Name
Friedrich-Schiller-University Jena
City
Jena
ZIP/Postal Code
07740
Country
Germany
Facility Name
Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Klinikum Ernst von Bergmann
City
Potsdam
ZIP/Postal Code
14467
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
28498880
Citation
Inhestern J, Schmalenberg H, Dietz A, Rotter N, Maschmeyer G, Jungehulsing M, Grosse-Thie C, Kuhnt T, Gorner M, Sudhoff H, Wittekindt C, Guntinas-Lichius O. A two-arm multicenter phase II trial of one cycle chemoselection split-dose docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). Ann Oncol. 2017 Aug 1;28(8):1917-1922. doi: 10.1093/annonc/mdx202.
Results Reference
derived
PubMed Identifier
26186556
Citation
Inhestern J, Oertel K, Stemmann V, Schmalenberg H, Dietz A, Rotter N, Veit J, Gorner M, Sudhoff H, Junghanss C, Wittekindt C, Pachmann K, Guntinas-Lichius O. Prognostic Role of Circulating Tumor Cells during Induction Chemotherapy Followed by Curative Surgery Combined with Postoperative Radiotherapy in Patients with Locally Advanced Oral and Oropharyngeal Squamous Cell Cancer. PLoS One. 2015 Jul 17;10(7):e0132901. doi: 10.1371/journal.pone.0132901. eCollection 2015.
Results Reference
derived
PubMed Identifier
23083061
Citation
Oertel K, Spiegel K, Schmalenberg H, Dietz A, Maschmeyer G, Kuhnt T, Sudhoff H, Wendt TG, Guntinas-Lichius O. Phase I trial of split-dose induction docetaxel, cisplatin, and 5-fluorouracil (TPF) chemotherapy followed by curative surgery combined with postoperative radiotherapy in patients with locally advanced oral and oropharyngeal squamous cell cancer (TISOC-1). BMC Cancer. 2012 Oct 20;12:483. doi: 10.1186/1471-2407-12-483.
Results Reference
derived

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

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