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) (Paccis-RCT)

This study is currently recruiting participants.
Verified April 2013 by University of Erlangen-Nürnberg Medical School
Sponsor:
Collaborator:
Deutsche Krebshilfe e.V., Bonn (Germany)
Information provided by (Responsible Party):
University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier:
NCT01126216
First received: May 17, 2010
Last updated: April 2, 2013
Last verified: April 2013

May 17, 2010
April 2, 2013
May 2010
June 2015   (final data collection date for primary outcome measure)
Disease free survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01126216 on ClinicalTrials.gov Archive Site
  • Overall Survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Distant metastasis free survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Local control [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Acute and Late Toxicity [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
  • Life Quality [ Time Frame: 4 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
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)
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

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Locally Advanced Head and Neck Cancer Stages III and IV A-B
  • Drug: Paclitaxel/Cisplatin
    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
    63,6 Gy accelerated hyperfractionated radiotherapy
  • Drug: 5-FU/Cisplatin
    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
    70,6 Gy accelerated hyperfractionated radiotherapy
  • 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
    Interventions:
    • Drug: Paclitaxel/Cisplatin
    • Radiation: Reduced RT
  • 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
    Interventions:
    • Drug: 5-FU/Cisplatin
    • Radiation: Standard RT
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
542
June 2018
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Rainer Fietkau, MD ++49(0)9131-85-33968 st-studiensekretariat@uk-erlangen.de
Contact: Markus Hecht, MD ++49(0)9131-85-33968 st-studiensekretariat@uk-erlangen.de
Germany
 
NCT01126216
Paccis-RCT_2005, 2005-003484-23, 107028
Yes
University of Erlangen-Nürnberg Medical School
University of Erlangen-Nürnberg Medical School
Deutsche Krebshilfe e.V., Bonn (Germany)
Study Director: Rainer Fietkau, MD Strahlenklinik, Universitätsklinikum Erlangen
University of Erlangen-Nürnberg Medical School
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP