Dose Reduced Radiotherapy (63,3 Gy) With Paclitaxel/Cisplatin Versus Standard Radiotherapy (70,2 Gy) With 5-Fluorouracil/Cisplatin in Locally Advanced Head and Neck Cancer (Stages III and IV A-B)

Condition(s) targeted: Locally Advanced Head and Neck Cancer Stages III and IV A-B

Intervention: Paclitaxel/Cisplatin (Drug); Reduced RT (Radiation); 5-FU/Cisplatin (Drug); Standard RT (Radiation)

Phase: Phase 3

Status: Recruiting

Sponsored by: University of Erlangen-Nürnberg Medical School

Official(s) and/or principal investigator(s):
Rainer Fietkau, MD, Study Director, Affiliation: Strahlenklinik, Universitätsklinikum Erlangen

Overall contact:
Rainer Fietkau, MD, Phone: ++49(0)9131-85-33968, Email: st-studiensekretariat@uk-erlangen.de

Standard treatment for patients with advanced, unresectable head and neck cancer is a platin-based simultaneous radiochemotherapy (RCT) (Pignon JP et al., Lancet 2000;355: 949-955). However, irradiation dose is still debatable regarding local tumor control and late toxicity. Moreover, it is still unclear which combination of different drugs might be more effective.

In recent years, new drugs have been introduced in the field of head and neck cancer. The Taxanes, namely Docetaxel and Paclitaxel, have been investigated in several phase I/II-studies, and showed promising results concerning locoregional control rates and survival data. The RTOG 97-03 trial (Garden et al., J Clin Oncol 2004; 22: 2856-64) compared a RCT either with Cisplatin/5-FU or Cisplatin/Paclitaxel. In this phase II-study an improvement of local tumor control and disease free survival of 15-20% in favour of the Cisplatin/Paclitaxel treatment arm was seen.

Therefore, our phase III-trial compares a standard RCT (70. 6 Gy) with Cisplatin/5-FU to a RCT with Cisplatin/Paclitaxel and reduced irradiation dose (63. 6 Gy). Primary endpoint is to proof superiority of the experimental Cisplatin/Paclitaxel treatment arm concerning disease-free-survival. Secondary endpoints are locoregional tumor control, overall survival and quality of life.

Official title: Randomised Phase-III-trial of Simultaneous Radiochemotherapy (RCT) of Locally Advanced Head and Neck Cancer in the Stages III and IV A-B: Comparing Dose Reduced Radiotherapy (63,6 Gy) With Paclitaxel/Cisplatin to Standard Radiotherapy (70,2 Gy) With 5-Fluorouracil/Cisplatin

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Disease free survival

Secondary outcome:

Overall Survival

Distant metastasis free survival

Local control

Acute and Late Toxicity

Life Quality

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Histologically proven, locally advanced stage III-IV A-B (UICC 2002) primary squamous

cell carcinoma of the oral cavity, the oropharynx, the hypopharynx, the supraglottic larynx

- Age ≥ 18

- Written informed consent for the participation in the clinical trial

Exclusion Criteria:

- Inadequate hepatic function: Bilirubin > 2,0 mg/dl, SGOT, SGPT, AP, Gamma-GT > 3 x

ULN

- Inadequate bone marrow function: leukocytes < 3,5 x 10^9/l, platelets < 100 x 10^9/l

or neutrophils < 1,5 x 10^9/l

- Serum creatinine > 1,5 mg/dl, creatinine clearance < 60ml/min

- Uncontrolled severe somatic or psychological disease: e. g. unstable angina pectoris;

myocardial infarction during the last 6 months; significant cardial rhythm disorders; apoplexy; high grade stenosis of the carotis; neurological or psychiatric disorders including convulsive disorders; dementia; psychosis; active uncontrolled infection or sepsis; liver cirrhosis; Child stage B,C; severe liver function disorders; marginal changes in the blood count; severe kidney damage; HIV-infection

- Acute infections

- Fertile women without adequate contraception during and up to 6 months after therapy

(the method of contraception has to be high effective as described in the Note for guidance on non-clinical safety studies for the conduct of human clinical trials for pharmaceuticals (CPMP/ICH/286/95 mod) and it has to be discussed with the investigator)

- Pregnant or breast feeding women

- Men, who are not willing to use adequate contraception during and up to 6 months

after therapy, that is discussed with the investigator

- ECOG-Status > 1

- Reduced hearing function (especially higher frequencies)

- Exsiccosis

- Neuropathy, caused by cisplatin

- Concurrent malignancies, with exception of adequately treated basal cell carcinoma of

the skin or in situ carcinoma or the cervix

- Prior radiotherapy of the neck or chemotherapy

- Distant metastasis

- Recurrent carcinoma in the head and neck region

- Prior neck-dissection or surgical intervention exceeding an exploratory excision

- Known intolerance to 5-Fluorouracil

- Known deficit of Dihydropyrimidine dehydrogenase (DPD)

- Simultaneous therapy with Brivudin or other inhibitors of DPD

- Known intolerance to Cisplatin or other substances that contain platin

- Known intolerance to Paclitaxel or one of the included substances, especially to

Poly(oxyethylene)Rhizinusöl/Macrogolglycerol ricinoleate

Rainer Fietkau, MD, Phone: ++49(0)9131-85-33968, Email: st-studiensekretariat@uk-erlangen.de

Klinikum Coburg, Strahlentherapie, DiaCura, Coburg 96450, Germany; Recruiting
Gerhard G. Grabenbauer, MD, Principal Investigator

Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Düsseldorf 40225, Germany; Recruiting
Stephan Gripp, MD, Principal Investigator

Universitätsklinikum Erlangen, Strahlenklinik, Erlangen 91054, Germany; Recruiting
Rainer Fietkau, MD, Principal Investigator

Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie, Frankfurt/M. 60590, Germany; Recruiting
Claus M. Rödel, MD, Principal Investigator

Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie, Göppingen 73035, Germany; Recruiting
Ulrike Schreck, MD, Principal Investigator

Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,, Homburg/Saar 66421, Germany; Recruiting
Christian Rübe, MD, Principal Investigator

Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke, Lübeck 23538, Germany; Recruiting
Barbara Wollenberg, MD, Principal Investigator

Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie, Mönchengladbach 41063, Germany; Recruiting
Hans Hoffmanns, MD, Principal Investigator

Klinikum München Pasing und Perlach, Klinik für HNO, München 81241, Germany; Recruiting
Peter Breinl, MD, Principal Investigator

Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie, Paderborn 33098, Germany; Recruiting
Horst Leber, MD, Principal Investigator

Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie, Regensburg 93053, Germany; Recruiting
Oliver Kölbl, MD, Principal Investigator

Universitätsklinikum Rostock, Klinik und Poliklinik für Stahlentherapie, Rostock 18059, Germany; Recruiting
Guido Hildebrandt, MD, Principal Investigator

Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde, Straubing 94315, Germany; Recruiting
Rainer Keerl, MD, Principal Investigator

MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie, Trier 54290, Germany; Recruiting
Birgit Siekmeyer, MD, Principal Investigator

Starting date: May 2010
Last updated: September 20, 2012