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

NCT ID: NCT01126216

Last Updated: 2021-05-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 221 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2019-06-30

Brief Summary

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

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.

Conditions

Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Paclitaxel/Cisplatin

Intervention Type: DRUG

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,

Reduced RT

Intervention Type: RADIATION

Experimental: 63,6 Gy accelerated hyperfractionated radiotherapy

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

Group Type: ACTIVE_COMPARATOR

5-FU/Cisplatin

Intervention Type: DRUG

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

Standard RT

Intervention Type: RADIATION

Active Comparator: 70,6 Gy accelerated hyperfractionated radiotherapy

Interventions

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,

Intervention Type: DRUG

Reduced RT

Experimental: 63,6 Gy accelerated hyperfractionated radiotherapy

Intervention Type: RADIATION

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

Intervention Type: DRUG

Standard RT

Active Comparator: 70,6 Gy accelerated hyperfractionated radiotherapy

Intervention Type: RADIATION

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Deutsche Krebshilfe e.V., Bonn (Germany)

OTHER

Sponsor Role: collaborator

University of Erlangen-Nürnberg Medical School

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rainer Fietkau, MD

Role: STUDY_DIRECTOR

Strahlenklinik, Universitätsklinikum Erlangen

Locations

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, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 32044419 (View on PubMed)

Other Identifiers

2005-003484-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

107028

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

Paccis-RCT_2005

Identifier Type: -

Identifier Source: org_study_id