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

Sponsor

University of Erlangen-Nürnberg Medical School (Other)

Overall Status

Terminated

CT.gov ID

NCT01126216

Collaborator

Deutsche Krebshilfe e.V., Bonn (Germany) (Other)

221

Enrollment

Locations

Arms

108

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer	Drug: Paclitaxel/Cisplatin Radiation: Reduced RT Drug: 5-FU/Cisplatin Radiation: Standard RT	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

221 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jun 1, 2010

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Jun 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reduced RT + Pacitaxel/Cisplatin 63,6 Gy accelerated hyperfractionated radiotherapy with 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, followed by a salvage operation or neck dissection if there is persisting tumor	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
Active Comparator: Standard RT + 5-Fluorouracil/Cisplatin 70,6 Gy accelerated hyperfractionated radiotherapy with 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, followed by a salvage operation or neck dissection if there is persisting tumor	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

Arm

Intervention/Treatment

Experimental: Reduced RT + Pacitaxel/Cisplatin

63,6 Gy accelerated hyperfractionated radiotherapy with 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, followed by a salvage operation or neck dissection if there is persisting tumor

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

Active Comparator: Standard RT + 5-Fluorouracil/Cisplatin

70,6 Gy accelerated hyperfractionated radiotherapy with 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, followed by a salvage operation or neck dissection if there is persisting tumor

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

Outcome Measures

Primary Outcome Measures

Disease free survival [3 years]

Secondary Outcome Measures

Overall Survival [3 years]
Distant metastasis free survival [3 years]
Local control [3 years]
Acute and Late Toxicity [4 years]
Life Quality [4 years]
HPV/p16-Status [End of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Klinikum Coburg, Strahlentherapie, DiaCura	Coburg	Germany	96450
2	Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie	Düsseldorf	Germany	40225
3	Universitätsklinikum Erlangen, Strahlenklinik	Erlangen	Germany	91054
4	Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie	Frankfurt/M.	Germany	60590
5	Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie	Göppingen	Germany	73035
6	Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,	Homburg/Saar	Germany	66421
7	Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke	Lübeck	Germany	23538
8	Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie	Mönchengladbach	Germany	41063
9	Klinikum München Pasing und Perlach, Klinik für HNO	München	Germany	81241
10	Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie	Paderborn	Germany	33098
11	Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie	Regensburg	Germany	93053
12	Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde	Straubing	Germany	94315
13	MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie	Trier	Germany	54290