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

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

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.

Study Overview

• Status: Completed
• Conditions: Oropharynx Cancer; Squamous Cell Carcinoma of the Oral Cavity
• Intervention / Treatment: Drug: Taxotere, Cisplatin, 5-Fluorouracil (5-FU)

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Bielefeld, Germany, 33604
    • Städt. Kliniken Bielefeld gem. GmbH
  • Jena, Germany, 07740
    • Friedrich-Schiller-University Jena
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde
  • Potsdam, Germany, 14467
    • Klinikum Ernst von Bergmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: Docetaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Orlando Guntinas-Lichius, Prof. Dr. med.
• Investigators: Principal Investigator: Orlando Guntinas-Lichius, Prof. Dr., Friedrich-Schiller-University Jena

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: April 14, 2010
• First Submitted That Met QC Criteria: April 20, 2010
• First Posted (Estimate): April 21, 2010

Study Record Updates

• Last Update Posted (Estimate): May 18, 2016
• Last Update Submitted That Met QC Criteria: May 17, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases; Mouth Diseases; Mouth Neoplasms; Oropharyngeal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Cisplatin; Fluorouracil
• Other Study ID Numbers: TISOC-1; 2009-011902-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No