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

Primary Purpose

Head and Neck Cancer

Status
Terminated
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Paclitaxel/Cisplatin
Reduced RT
5-FU/Cisplatin
Standard RT
Sponsored by
University of Erlangen-Nürnberg Medical School
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Radiochemotherapy, head and neck cancer, Paclitaxel, Cisplatin, 5-FU

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • Klinikum Coburg, Strahlentherapie, DiaCura
  • Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie
  • Universitätsklinikum Erlangen, Strahlenklinik
  • Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie
  • Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie
  • Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,
  • Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke
  • Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie
  • Klinikum München Pasing und Perlach, Klinik für HNO
  • Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie
  • Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie
  • Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde
  • MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Reduced RT + Pacitaxel/Cisplatin

Standard RT + 5-Fluorouracil/Cisplatin

Arm Description

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

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

Outcomes

Primary Outcome Measures

Disease free survival

Secondary Outcome Measures

Overall Survival
Distant metastasis free survival
Local control
Acute and Late Toxicity
Life Quality
HPV/p16-Status

Full Information

First Posted
May 17, 2010
Last Updated
April 28, 2021
Sponsor
University of Erlangen-Nürnberg Medical School
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany)
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1. Study Identification

Unique Protocol Identification Number
NCT01126216
Brief Title
Reduced Radiotherapy With Pac/Cis vs Standard Radiotherapy With 5-FU/Cis in Locally Advanced Head and Neck Cancer
Acronym
Paccis-RCT
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Terminated
Why Stopped
After an Interims analysis the Data Safety Monitoring board recommended this because no significant difference between the two arms was seen and was not expected with an reasonable recruitment of patients. No interruptions of the trial were made.
Study Start Date
June 2010 (Actual)
Primary Completion Date
June 2015 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Erlangen-Nürnberg Medical School
Collaborators
Deutsche Krebshilfe e.V., Bonn (Germany)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Radiochemotherapy, head and neck cancer, Paclitaxel, Cisplatin, 5-FU

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
221 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Reduced RT + Pacitaxel/Cisplatin
Arm Type
Experimental
Arm Description
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
Arm Title
Standard RT + 5-Fluorouracil/Cisplatin
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Paclitaxel/Cisplatin
Intervention Description
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
Radiation
Intervention Name(s)
Reduced RT
Intervention Description
Experimental: 63,6 Gy accelerated hyperfractionated radiotherapy
Intervention Type
Drug
Intervention Name(s)
5-FU/Cisplatin
Intervention Description
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
Radiation
Intervention Name(s)
Standard RT
Intervention Description
Active Comparator: 70,6 Gy accelerated hyperfractionated radiotherapy
Primary Outcome Measure Information:
Title
Disease free survival
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Overall Survival
Time Frame
3 years
Title
Distant metastasis free survival
Time Frame
3 years
Title
Local control
Time Frame
3 years
Title
Acute and Late Toxicity
Time Frame
4 years
Title
Life Quality
Time Frame
4 years
Title
HPV/p16-Status
Time Frame
End of study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rainer Fietkau, MD
Organizational Affiliation
Strahlenklinik, Universitätsklinikum Erlangen
Official's Role
Study Director
Facility Information:
Facility Name
Klinikum Coburg, Strahlentherapie, DiaCura
City
Coburg
ZIP/Postal Code
96450
Country
Germany
Facility Name
Universitätsklinikum Düsseldorf, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie
City
Düsseldorf
ZIP/Postal Code
40225
Country
Germany
Facility Name
Universitätsklinikum Erlangen, Strahlenklinik
City
Erlangen
ZIP/Postal Code
91054
Country
Germany
Facility Name
Universitätsklinikum Frankfurt, Klinik für Strahlentherapie und Radioonkologie
City
Frankfurt/M.
ZIP/Postal Code
60590
Country
Germany
Facility Name
Klinikum am Eichert, Praxis für Strahlentherapie und Klinik für Radioonkologie
City
Göppingen
ZIP/Postal Code
73035
Country
Germany
Facility Name
Universitätsklinikum des Saarlandes, Klinik für Strahlentherapie und Radioonkologie,
City
Homburg/Saar
ZIP/Postal Code
66421
Country
Germany
Facility Name
Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Klinik und Poliklinik für Hals-Nasen- und Ohrenkranke
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
Kliniken Maria Hilf GmbH Mönchengladbach, Klinik für Strahlentherapie
City
Mönchengladbach
ZIP/Postal Code
41063
Country
Germany
Facility Name
Klinikum München Pasing und Perlach, Klinik für HNO
City
München
ZIP/Postal Code
81241
Country
Germany
Facility Name
Brüderkrankenhaus st. Josef Paderborn, Klinik für Strahlentherapie
City
Paderborn
ZIP/Postal Code
33098
Country
Germany
Facility Name
Universitätsklinikum Regensburg, Klinik und Poliklinik für Strahlentherapie
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Klinikum St. Elisabeth Straubing, Klinik für Hals-Nasen-Ohren-Heilkunde
City
Straubing
ZIP/Postal Code
94315
Country
Germany
Facility Name
MVZ am Klinikum Mutterhaus der Borrmäerinnen, Strahlentherapie
City
Trier
ZIP/Postal Code
54290
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
32044419
Citation
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.
Results Reference
derived

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

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