Clinical trial NCT01108042: 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
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Oropharynx Cancer
Squamous Cell Carcinoma of the Oral Cavity
Lead sponsor: University of Jena
Sponsor class: OTHER
First posted: 2010-04-21
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Determination of progression-free survival after 2 years
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival after 2 years
timeFrame: after 2 years
measure: Determination of the efficacy of the induction therapy
timeFrame: after 1, 12 and 24 months
measure: Function of swallowing according the penetration-aspiration-scale
timeFrame: 0,1, 6, 12, 18, 24 months
measure: Adverse events as a measure of safety and tolerability
timeFrame: once a week
measure: Quality of life
timeFrame: 0,1, 6, 12, 18, 24 months
Other outcomes:
Locations:
city: Bielefeld
country: Germany
facility: Städt. Kliniken Bielefeld gem. GmbH
city: Jena
country: Germany
facility: Friedrich-Schiller-University Jena
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig - Klinik und Poliklinik für HNO-Heilkunde
city: Potsdam
country: Germany
facility: Klinikum Ernst von Bergmann
Study officials:
affiliation: Friedrich-Schiller-University Jena
name: Orlando Guntinas-Lichius, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.