Clinical trial NCT01126216: Reduced Radiotherapy With Pac/Cis vs Standard Radiotherapy With 5-FU/Cis in Locally Advanced Head and Neck Cancer
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Head and Neck Cancer
Keywords: Radiochemotherapy
head and neck cancer
Paclitaxel
Cisplatin
5-FU
Lead sponsor: University of Erlangen-Nürnberg Medical School
Sponsor class: OTHER
Collaborators: name: Deutsche Krebshilfe e.V., Bonn (Germany)
First posted: 2010-05-19
Enrollment: 221
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Reduced RT with Pac/Cis vs. standard RCT with 5-FU/Cis

Detailed description: 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.

Eligibility 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

Primary outcomes:
measure: Disease free survival
timeFrame: 3 years
Secondary outcomes:
measure: Overall Survival
timeFrame: 3 years
measure: Distant metastasis free survival
timeFrame: 3 years
measure: Local control
timeFrame: 3 years
measure: Acute and Late Toxicity
timeFrame: 4 years
measure: Life Quality
timeFrame: 4 years
measure: HPV/p16-Status
timeFrame: End of study
Other outcomes:
Locations:
city: Coburg
country: Germany
facility: Klinikum Coburg, Strahlentherapie, DiaCura
city: Düsseldorf
country: Germany
facility: Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen, Strahlenklinik
city: Frankfurt/M.
country: Germany
facility: Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie
city: Göppingen
country: Germany
facility: Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie
city: Homburg/Saar
country: Germany
facility: Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke
city: Mönchengladbach
country: Germany
facility: Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie
city: München
country: Germany
facility: Klinikum München Pasing und Perlach, Klinik für HNO
city: Paderborn
country: Germany
facility: Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie
city: Straubing
country: Germany
facility: Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde
city: Trier
country: Germany
facility: MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie
Study officials:
affiliation: Strahlenklinik, Universitätsklinikum Erlangen
name: Rainer Fietkau, MD
role: STUDY_DIRECTOR
References:
citation: Fietkau R, Hecht M, Hofner B, Lubgan D, Iro H, Gefeller O, Rodel C, Hautmann MG, Kolbl O, Salay A, Rube C, Melchior P, Breinl P, Krings W, Gripp S, Wollenberg B, Keerl R, Schreck U, Siekmeyer B, Grabenbauer GG, Balermpas P; PacCis-Study Group. Randomized phase-III-trial of concurrent chemoradiation for locally advanced head and neck cancer comparing dose reduced radiotherapy with paclitaxel/cisplatin to standard radiotherapy with fluorouracil/cisplatin: The PacCis-trial. Radiother Oncol. 2020 Mar;144:209-217. doi: 10.1016/j.radonc.2020.01.016. Epub 2020 Feb 7.