E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Head and Neck cancer, Stage III-IV A-B |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026518 |
E.1.2 | Term | Malignant neoplasm of supraglottis stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026185 |
E.1.2 | Term | Malignant neoplasm of oropharynx, unspecified |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041862 |
E.1.2 | Term | Squamous cell carcinoma of the oral cavity stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041863 |
E.1.2 | Term | Squamous cell carcinoma of the oral cavity stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041855 |
E.1.2 | Term | Squamous cell carcinoma of the hypopharynx stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10041854 |
E.1.2 | Term | Squamous cell carcinoma of the hypopharynx stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10026519 |
E.1.2 | Term | Malignant neoplasm of supraglottis stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the superiority of dose reduced radiotherapy (63.6 Gy) with Paclitaxel/Cisplatin versus standard radiotherapy (70.2 Gy) with 5-FU/Cisplatin:
NED-Survival |
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E.2.2 | Secondary objectives of the trial |
Overall survival
Locoregional tumor control rate
Quality of life |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Tumor infiltrating inflammatory cells: Progression- and resistance factor of head and neck squamous cell carcinoma?
(Substudy is included in the protocol, therefore date and version are identical to the protocol)
Objectives:
Analysis of tumor infiltrating lymphocytes as prognostic factor in the treatment of squamous cell carcinoma with simultaneous radiochemotherapy
Methods:
Tissue-Micro-Arrays, FACS-Analysis, PCR |
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E.3 | Principal inclusion criteria |
1. 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
2. Age ≥ 18
3. Written informed consent for the participation in the clinical trial
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E.4 | Principal exclusion criteria |
1. Unadequate hepatic function:
Bilirubin > 2,0 mg/dl, SGOT, SGPT, AP, Gamma-GT > 3 x ULN
2. Unadequate bone marrow function:
Leukocytes < 3,5 x 10^9/l, Platelets < 100 x 10^9/l or Neutrophile < 1,5 x 10^9/l
3. Serum creatinine > 1,5 mg/dl, Creatinine-clearance < 60ml/min
4. Uncontrolled severe somatic or psychological disease:
- 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
5. Acute infections
6. 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 teh Note for guidance on non-clinical safety studies for the conduct of human clinical reials for pharmaceuticals (CPMP/ICH/286/95 mod) and it has to be discussed with the investigator)
7. Pregnant or breast feeding women
8. Men, who are not willing to use adequate contraception during and up to 6 months after therapy, that is discussed with the investigator
9. ECOG-Status > 1
10. Reduced hearing function (especially higher frequencies)
11. Exsiccose
12. Neuropathy, caused by cisplatin
13. Concurrent malignancies, with exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma or the cervix
14. Prior radiotherapy of the neck or chemotherapy
15. Distant metastasis
16. Recurrent carcinoma in the head and neck region
17. Prior neck-dissection or surgical intervention exceeding an exploratory excision
18. Known intolerance to 5-Fluorouracil
19. Known deficite of Dihydropyrimidindehydrogenase (DPD)
20. Simultaneous therapy with Brivudin or other inhibitors of DPD
21. Known intolerance to Cisplatin or other substances that contain platin
22. Known intolerance to Paclitaxel or one of the included substances, especially to Poly(oxyethylen)-35-Rhizinusöl/Macrogolglycerolricinoleat
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Overall survival
Disease free survival
Locoregional tumor control rate
Acute and long term toxicity
Quality of life
Analysis of HPV/p16-status |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 9 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 9 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |