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. (see Contacts and Locations)
Verified July 2014 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: July 1, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Locally Advanced Head and Neck Cancer Stages III and IV A-B
Drug: Paclitaxel/Cisplatin
Radiation: Reduced RT
Drug: 5-FU/Cisplatin
Radiation: Standard RT
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Erlangen-Nürnberg Medical School:

Primary Outcome Measures:
  • Disease free survival [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 542
Study Start Date: May 2010
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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
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
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01126216

Contacts
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

Locations
Germany
Klinikum Coburg, Strahlentherapie, DiaCura Recruiting
Coburg, Germany, 96450
Principal Investigator: Gerhard G. Grabenbauer, MD         
Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie Recruiting
Düsseldorf, Germany, 40225
Principal Investigator: Stephan Gripp, MD         
Universitätsklinikum Erlangen, Strahlenklinik Recruiting
Erlangen, Germany, 91054
Principal Investigator: Rainer Fietkau, MD         
Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie Recruiting
Frankfurt/M., Germany, 60590
Principal Investigator: Claus M. Rödel, MD         
Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie Recruiting
Göppingen, Germany, 73035
Principal Investigator: Ulrike Schreck, MD         
Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie, Recruiting
Homburg/Saar, Germany, 66421
Principal Investigator: Christian Rübe, MD         
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke Recruiting
Lübeck, Germany, 23538
Principal Investigator: Barbara Wollenberg, MD         
Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie Recruiting
Mönchengladbach, Germany, 41063
Principal Investigator: Hans Hoffmanns, MD         
Klinikum München Pasing und Perlach, Klinik für HNO Recruiting
München, Germany, 81241
Principal Investigator: Peter Breinl, MD         
Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie Recruiting
Paderborn, Germany, 33098
Principal Investigator: Horst Leber, MD         
Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie Recruiting
Regensburg, Germany, 93053
Principal Investigator: Oliver Kölbl, MD         
Universitätsklinikum Rostock, Klinik und Poliklinik für Stahlentherapie Withdrawn
Rostock, Germany, 18059
Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde Recruiting
Straubing, Germany, 94315
Principal Investigator: Rainer Keerl, MD         
MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie Recruiting
Trier, Germany, 54290
Principal Investigator: Birgit Siekmeyer, MD         
Sponsors and Collaborators
University of Erlangen-Nürnberg Medical School
Deutsche Krebshilfe e.V., Bonn (Germany)
Investigators
Study Director: Rainer Fietkau, MD Strahlenklinik, Universitätsklinikum Erlangen
  More Information

No publications provided

Responsible Party: University of Erlangen-Nürnberg Medical School
ClinicalTrials.gov Identifier: NCT01126216     History of Changes
Other Study ID Numbers: Paccis-RCT_2005, 2005-003484-23, 107028
Study First Received: May 17, 2010
Last Updated: July 1, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by University of Erlangen-Nürnberg Medical School:
Radiochemotherapy
head and neck cancer
Paclitaxel
Cisplatin
5-FU

Additional relevant MeSH terms:
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Fluorouracil
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on August 01, 2014