E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
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 |
The main objective of this study is to assess the feasibility, tolerability and the maximum tolerated dose (MTD) of oral AT-101 in combination with concurrent cisplatin-based chemotherapy and radiotherapy (RT) in advanced HNSCC, as a guidance for the recommended dose in future studies. |
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E.2.2 | Secondary objectives of the trial |
Additional objectives include the exploration of mechanisms, involved in the therapeutic effect of the different modalities in this combined modality treatment, exploration of pharmacokinetics of AT-101, and documentation of therapeutic effects. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically proven squamous cell carcinoma of the head and neck • Oral cavity, oropharyngeal, or hypopharyngeal carcinoma • Inoperable TNM stage III/IV, M0 • Patient must have measurable disease • age > 18 years • performance status WHO 0-2 (see Appendix B) • No prior radiation therapy to head and neck region • No prior cisplatin-based chemotherapy • Adequate laboratory results: o WBC > 4.0 o platelets > 100,000 o calculated or 24 hour creatinine clearance > 50 ml/min o ASAT/ALAT < 2.5 times upper limit of normal range o Bilirubin < 1.5 x upper limit of institution's normal range • No uncontrolled arrhythmia • No breast feeding or pregnancy • Willingness to use contraception by a method that is deemed effective by the Investigator throughout the treatment period and for at least 30 days following the last dose of therapy • Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule • Entry criteria for translational research: o Willing and able to undergo blood sampling, harvesting of buccal smears and tumor biopsy (mandatory) o Willing and able to undergo skin biopsy and nuclear scanning (optional) • Willing and able to undergo blood sampling for pharmacokinetics • Signed written informed consent before entry into study.
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E.4 | Principal exclusion criteria |
• Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel are excluded. Subjects with ulcerative colitis, inflammatory bowel disease, or partial or complete small bowel obstruction are also excluded. • Patients with Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification (see Appendix C) are excluded. • Patients with known active symptomatic fungal, bacterial and/or viral infection including active HIV are excluded. Note: protocol does not require screening for viruses; however, patients with known active infections are excluded.
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E.5 End points |
E.5.1 | Primary end point(s) |
• Tolerability of combined treatment consisting of oral AT-101 and concurrent cisplatin-based chemoradiation, i.e. the definition of a feasible, safely administrable daily dose of oral AT-101, close to the MTD, in combination with standard chemoradiation. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |