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

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

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

Study Overview

• Status: Terminated
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Drug: Paclitaxel/Cisplatin; Radiation: Reduced RT; Drug: 5-FU/Cisplatin; Radiation: Standard RT

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 Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Coburg, Germany, 96450
    • Klinikum Coburg, Strahlentherapie, DiaCura
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen, Strahlenklinik
  • Frankfurt/M., Germany, 60590
    • Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie
  • Göppingen, Germany, 73035
    • Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie
  • Homburg/Saar, Germany, 66421
    • Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie
  • München, Germany, 81241
    • Klinikum München Pasing und Perlach, Klinik für HNO
  • Paderborn, Germany, 33098
    • Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie
  • Straubing, Germany, 94315
    • Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde
  • Trier, Germany, 54290
    • MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Disease free survival	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Erlangen-Nürnberg Medical School
• Collaborators: Deutsche Krebshilfe e.V., Bonn (Germany)

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2010
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2019

Study Registration Dates

• First Submitted: May 17, 2010
• First Submitted That Met QC Criteria: May 17, 2010
• First Posted (ESTIMATE): May 19, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 4, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Cisplatin; head and neck cancer; Paclitaxel; 5-FU; Radiochemotherapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: Paccis-RCT_2005; 2005-003484-23 (EUDRACT_NUMBER); 107028 (OTHER_GRANT: Deutsche Krebshilfe e. V.)