E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced head and neck cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Advanced head and neck cancer. |
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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 | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 assess the tolerability of Redaporfin following single ascending doses of Redaporfin activated with a dose of 50 J/cm2 of laser light at 749±3 nm. |
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E.2.2 | Secondary objectives of the trial |
To explore the Redaporfin dose that has anti-tumour effect following activation with a dose of 50 J/cm2 of laser light at 749±3 nm. To measure the plasma concentrations of Redaporfin and its metabolites and to determine the corresponding pharmacokinetic parameters.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Able and willing to give written informed consent and adhere to all requirements of the study. 2. Man or non-pregnant and non-breast feeding woman. 3. Age ≥ 18 years. 4. Karnofsky performance status of 60% (60% = requiring some help, can take care of most personal requirements) or greater. 5. With histologically confirmed diagnosis of recurrent/refractory squamous cell carcinoma (including variants such as verrucous carcinoma, spindle cell carcinoma, carcinoma not otherwise specified (NOS), etc.) of the head/neck. 6. Clearly visible tumour on the oral cavity or cutaneous surface and that is locally accessible for surface irradiation using a microlens optic fibre. 7. Head and neck squamous cell carcinoma (HNSCC) progressing after first line of palliative chemotherapy OR progressing ≤ 6 months after radical chemoradiotherapy OR considered not suitable for standard anti-neoplastic treatment by a multidisciplinary team. 8. Absolute granulocyte count >1,500 cells/mL. 9. Platelet count >100,000 cells/mL. 10. Haemoglobin >9.0 g/dL (the use of transfusion or other intervention to achieve Hgb >9.0 g/dL is acceptable). 11. Total bilirubin < 2 times the upper limit of normal (ULN). 12. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN. 13. Serum creatinine < 2 times the ULN or creatinine clearance (CrCL) >50 mL/min determined by 24-h urine collection or estimated by Cockroff-Gault formula: CrCL male = [(140-age) x (weight in kg] /[(serum Cr mg/dL) x (72)]; CrCL female = 0.85 x (CrCL male). 14. If woman, she is not of childbearing potential or she agrees to use a medically effective means of birth control. 15. If man, he is not sexually active or he agrees to use a medically effective means of birth control. |
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E.4 | Principal exclusion criteria |
1. Life expectancy less than 6 months. 2. Known hypersensitivity to porphyrins or any of the formulation ingredients. 3. History of severe hypersensitivity reactions to any drugs. 4. Porphyria or other diseases exacerbated by light. 5. Metastatic or locoregional progressive disease not amenable for complete treatment by PDT. 6. Tumours known to be eroding into a major blood vessel in or adjacent to the irradiation site. 7. Planned skin phototherapy session within the study timeframe. 8. Planned surgical procedure within the study timeframe. 9. Coexisting ophthalmic disease likely to require slit-lamp examination within the study timeframe. 10. Existing therapy with a photosensitising agent. 11. Unacceptable laboratory abnormalities. 12. Clinically relevant 12-lead ECG abnormalities. 13. Unstable angina and/or congestive heart failure requiring hospitalisation within 6 months prior to screening. 14. Myocardial infarction within 6 months prior to screening. 15. Cannot communicate reliably with the investigator. 16. Unlikely to co-operate with the requirements of the study. 17. Contra-indication to MRI with gadolinium (e.g., use of pacemaker, allergy to gadolinium). 18. Participation in a clinical trial within 2 months prior to screening. 19. If woman, she has a positive pregnancy test. 20. If woman, she is currently breast-feeding. |
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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) |
Pharmacokinetics (PK): Cmax, AUC0-t, AUC0-∞, AUC0- t/AUC0-∞, Tmax, t½, λz, Vd and CL Depth of tumour necrosis, as assessed by diffusion-weighted and perfusion MRI with gadolinium.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
PK: before infusion start; at infusion completion; and at 0.08 (5 minutes), 0.5 (30 minutes), 0.75 (45 minutes), 1, 3, 6, 12, 24, 48 and 72 h post-infusion completion. Depth of tumour necrosis: at admission, day 7, day 21 of each PDT treatment period and at the end of follow-up phase. |
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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 | Yes |
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) | 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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
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.8.5 | 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 | 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 | |