Reduced Radiotherapy With Pac/Cis vs Standard Radiotherapy With 5-FU/Cis in Locally Advanced Head and Neck Cancer

Head and Neck Cancer Clinical Trial

— Paccis-RCT  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01126216
• Other study ID #: Paccis-RCT_2005
• Secondary ID: 2005-003484-2310
• Status: Terminated
• Phase: Phase 3
• Start date: June 2010
• Est. completion date: June 2019

Study information

• Verified date: August 2017
• Source: University of Erlangen-Nürnberg Medical School
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 221
• Est. completion date: June 2019
• Est. primary completion date: June 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Drug:
• Paclitaxel/Cisplatin
Experimental: Paclitaxel (20mg/m^2/d) on days 2, 5, 8, 11 and 25, 30, 33, 36) and Cisplatin (20mg/m^2/d) on days 1-4 and 29-32,

Radiation:
• Reduced RT
Experimental: 63,6 Gy accelerated hyperfractionated radiotherapy

Drug:
• 5-FU/Cisplatin
Active Comparator: 5-Fluorouracil(600mg/m^2/d) on days 1-5 and 29-33) and Cisplatin (20mg/m^2/d) on days 1-5 and 29-33

Radiation:
• Standard RT
Active Comparator: 70,6 Gy accelerated hyperfractionated radiotherapy

Locations

Country	Name	City	State
Germany	Klinikum Coburg, Strahlentherapie, DiaCura	Coburg
Germany	Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie	Düsseldorf
Germany	Universitätsklinikum Erlangen, Strahlenklinik	Erlangen
Germany	Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie	Frankfurt/M.
Germany	Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie	Göppingen
Germany	Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,	Homburg/Saar
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke	Lübeck
Germany	Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie	Mönchengladbach
Germany	Klinikum München Pasing und Perlach, Klinik für HNO	München
Germany	Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie	Paderborn
Germany	Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie	Regensburg
Germany	Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde	Straubing
Germany	MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie	Trier

Sponsors (2)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School	Deutsche Krebshilfe e.V., Bonn (Germany)

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease free survival		3 years
Secondary	Overall Survival		3 years
Secondary	Distant metastasis free survival		3 years
Secondary	Local control		3 years
Secondary	Acute and Late Toxicity		4 years
Secondary	Life Quality		4 years
Secondary	HPV/p16-Status		End of study